Biochem

ALANINE
Alanine is an -amino acid with the chemical formula HO2CCH(NH2)CH3. The L-isomer is one of the 20
proteinogenic amino acids, i.e. the building blocks of proteins. Its three letter code is ala, its one letter
code is A, and its codons are GCU, GCC, GCA, and GCG.[1] It is classified as an nonpolar amino acid. Lalanine is second only to leucine, accounting for 7.8% of the primary structure in a sample of 1,150
proteins [1]. D-alanine occurs in bacterial cell walls and in some peptide antibiotics.
1. Structure
The -carbon atom of alanine is bound with a methyl group (-CH3), making it one of the simplest -amino
acids with respect to molecular structure and also resulting in alanine being classified as an aliphatic
amino acid. The methyl group of alanine is non-reactive and is thus almost never directly involved in
protein function.
2. Biosynthesis
Alanine is most commonly produced by reductive amination of pyruvate. Because transamination
reactions are readily reversible and pyruvate pervasive, alanine can be easily formed and thus has close
links to metabolic pathways such as glycolysis, gluconeogenesis, and the citric acid cycle. It also arises
together with lactate and generates glucose from protein via the alanine cycle.
3. Sources
Any protein-containing food such as meat, poultry, fish, eggs or dairy products is rich in alanine. Racemic
alanine can be prepared via the addition of hydrogen cyanide and ammonia to acetaldehyde by the
Strecker-reaction.
ARGININE
Arginine (symbol Arg or R) is an -amino acid. The L-form is one of the 20 most common natural amino
acids. In mammals, arginine is classified as a semiessential or conditionally essential amino acid,
depending on the developmental stage and health status of the individual. Infants are unable to effectively
synthesize arginine, making it nutritionally essential for infants. Adults, however, are able to synthesize
arginine in the urea cycle.
Arginine was first isolated from a lupin seedling extract in 1886 by the Swiss chemist Ernst Schulze.
1. Structure
Arginine can be considered to be a basic amino acid because the part of the side chain nearest to the
backbone is long, carbon-containing and hydrophobic, whereas the end of the side chain is a complex
guanidinium group. With a pKa of 12.48, the guanidinium group is positively charged in neutral, acidic and
even most basic environments. Because of the conjugation between the double bond and the nitrogen
lone pairs, the positive charge is delocalized. This group is able to form multiple H-bonds.
2. Synthesis
Arginine is synthesized from citrulline by the sequential action of the cytosolic enzymes argininosuccinate
synthetase (ASS) and argininosuccinate lyase (ASL). This is energetically costly, as the synthesis of each
molecule of argininosuccinate requires hydrolysis of adenosine triphosphate (ATP) to adenosine
monophosphate (AMP); i.e., two ATP equivalents.
Citrulline can be derived from multiple sources:
from arginine via nitric oxide synthase (NOS);
from ornithine via catabolism of proline or glutamine/glutamate;
from asymmetric dimethylarginine (ADMA) via DDAH.
3. Functions
Arginine plays an important role in cell division, the healing of wounds, removing ammonia from the body,
immune function, and the release of hormones. Arginine, taken in combination with pycnogenol[2] or
yohimbine, has also been used as a treatment for erectile dysfunction.
3.1. In proteins
The geometry, charge distribution and ability to form multiple H-bonds make arginine ideal for binding
negatively charged groups. For this reason arginine prefers to be on the outside of the proteins where it
can interact with the polar environment. Incorporated in proteins, arginine can also be converted to
citrulline by PAD enzymes. In addition, arginine can be methylated by protein methyltransferases.
3.2. As a precursor
Arginine is the immediate precursor of NO, urea, ornithine and agmatine; is necessary for the synthesis of
creatine; and can not be used for the synthesis of polyamines (mainly through ornithine and to a lesser
degree through agmatine), citrulline, and glutamate. For being a precursor of NO, (relaxes blood vessels),
arginine is used in many conditions where vasodilation is required. The presence of asymmetric
dimethylarginine (ADMA), a close relative, inhibits the nitric oxide reaction; therefore, ADMA is considered
a marker for vascular disease, just as L-arginine is considered a sign of a healthy endothelium.
3.3. Implication in herpes simplex viral replication
Tissues culture studies have shown the suppression of viral replication when the lysine to arginine ratio in
vitro favors lysine. The therapeutic consequence of this finding is unclear, but dietary arginine may affect
the effectiveness of lysine supplementation.
3.4. Implication in contributing to risk of death from heart disease
A recent Johns Hopkins study testing the addition of L-arginine to standard postinfarction treatment has
implicated L-arginine supplementation with an increased risk of death in patients recovering from heart
attack.[5] This study has been discussed in some detail in : "Reverse Heart Disease Now" by Stephen T
Sinatra MD and James C Roberts MD, publ. Wiley 2006 ISBN 0-471-74704-1 at pp 111 -113.
3.5. Growth hormone
Arginine increases the production of growth hormone.[6] Reports of its effects on male muscular
development are not clearly proven.
4. Prolactin
Although there haven't been thorough studies, some sources claim that arginine helps release prolactin,
an estrogenic compound which is associated with lactation, and like all estrogenic compounds may curb
the secretion of testosterone (citation needed). Thus some bodybuilders stay away from pure arginine,
intaking only amounts naturally found in protein.
5. Food sources
Arginine is found in chocolate, wheat germ and flour, buckwheat, granola, oatmeal, dairy products
(cottage cheese, ricotta, nonfat dry milk, skim yogurt), beef (roasts, steaks), pork (Canadian bacon, ham),
nuts (coconut, pecans, cashews, walnuts, almonds, Brazil nuts, hazel nuts, peanuts), seeds (pumpkin,
sesame, sunflower), poultry (chicken and turkey light meat), wild game (pheasant, quail), seafood
(halibut, lobster, salmon, shrimp, snails, tuna in water), chick peas, cooked soybeans[7], and some
energy drinks.
6. References
1. Enzymes of arginine metabolism J Nutr. 2004 Oct; 134(10 Suppl): 2743S-2747S.
2. Stanislavov, R. and Nikolova. 2003. Treatment of Erectile Dysfunction with Pycnogenol and L-arginine.
Journal
of
Sex
and
Marital
Therapy,
29(3):
207
213.
3. Lebret, T., Herva, J. M., Gornyb, P., Worcelc, M. and Botto, H. 2002. Efficacy and Safety of a Novel
Combination of L-Arginine Glutamate and Yohimbine Hydrochloride: A New Oral Therapy for Erectile
Dysfunction.
European
Urology
41(6):
608-613.
4. Griffith RS, Norins AL, Kagan C. (1978). "A multicentered study of lysine therapy in Herpes simplex
infection".
Dermatologica.
156
(5):
257-267.
5. Arginine Therapy in Acute Myocardial Infarction JAMA. 2006 Jan; Vol.295 #1: 58-64.
6. Alba-Roth J, Mller O, Schopohl J, von Werder K (1988). "Arginine stimulates growth hormone
secretion by suppressing endogenous somatostatin secretion". J Clin Endocrinol Metab 67 (6): 1186-9.
7. L-Arginine Supplements Nitric Oxide Scientific Studies Food Sources.
7. External links
NIST Chemistry Webbook
Asparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side
chain's functional group. It is considered a non-essential amino acid.
Its three-letter abbreviation is Asn, and its one-letter abbreviation is N. A three-letter designation for either
asparagine or aspartic acid is Asx (one-letter abbreviation: B).
A reaction between asparagine and reducing sugars or reactive carbonyls produces acrylamide (acrylic
amide) in food when heated to sufficient temperature, i.e. baking. These occur primarily in baked goods
such as french fries, potato chips, and roasted coffee.
1. History
Asparagine was first isolated in 1806 from asparagus juice, in which it is abundant - hence its name becoming the first amino acid to be isolated. The characteristic smell observed in the urine of individuals
after their consumption of asparagus is attributed to various metabolic byproducts of asparagine: in 1891,
Marceli Nencki claimed that the substance responsible was methanethiol, and Robert White's 1975
research indicated that the substances were various thioesters. Other likely possibilities include
asparagine aminosuccinic monoamide. Allison and McWhirter's 1956 research[1] indicated that some
individuals do not produce this odor after asparagus consumption, and that this is autosomal; however, a
re-examination in 1980 showed that these individuals are, rather, not able to detect the odor.
2. Structural function in proteins
Since the asparagine side chain can make efficient hydrogen bond interactions with the peptide
backbone, asparagines are often found near the beginning and end of alpha-helices, and in turn motifs in
beta sheets. Its role can be thought as "capping" the hydrogen bond interactions which would otherwise
need to be satisfied by the polypeptide backbone. Glutamines have an extra methylene group, have more
conformational
entropy
and
thus
are
less
useful
in
this
regard.
Asparagine also provides key sites for N-linked glycosylation, modification of the protein chain with the
addition of carbohydrate chains.
3. Biosynthesis
Asparagine is not an essential amino acid, which means that it can be synthesized from central metabolic
pathway intermediates in humans and is not required in the diet. The precursor to asparagine is
oxaloacetate. Oxaloacetate is converted to aspartate using a transaminase enzyme. The enzyme
transfers the amino group from glutamate to oxaloacetate producing -ketoglutarate and aspartate. The
enzyme asparagine synthetase produces asparagine, AMP, glutamate, and pyrophosphate from
aspartate, glutamine, and ATP. In the asparagine synthetase reaction, ATP is used to activate aspartate,
forming -aspartyl-AMP. Glutamine donates an ammonium group which reacts with -aspartyl-AMP to
form asparagine and free AMP.
The biosynthesis of asparagine from oxaloacetate

4. Degradation
Aspartate is a glucogenic amino acid. L-asparginase hydrolyzes the amide group to form aspartate and
ammonium. A transaminase converts the aspartate to oxaloacetate which can then be metabolized in the
citric acid cycle or gluconeogenesis.
5. Function
The nervous system needs asparagine to maintain the equilibrium, as well as in amino acid
transformation. It also plays an important role in the synthesis of ammonia.
6. Sources
Asparagus, dairy products, potatoes, beef, poultry, meat, and eggs.
7. References
1. ALLISON AC, MCWHIRTER KG (1956). "Two unifactorial characters for which man is polymorphic".
Nature 178 (4536): 748-9.
Aspartic Acid
Aspartic acid is an -amino acid with the chemical formula HO2CCH(NH2)CH2CO2H. The L-isomer is
one of the 20 proteinogenic amino acids, i.e. the building blocks of proteins. Its three letter code is asp, its
one letter code is D, and its codons are GAU and GAC.[1] It is classified as an acidic amino acid, together
with glutamic acid. Aspartic acid is pervasive in biosynthesis.
1. Role in biosynthesis of amino acids

Aspartic acid is non-essential in mammals, being produced from oxaloacetate by transamination. In plants
and microorganisms, aspartic acid is the precursor to several amino acids, including four that are
essential: methionine, threonine, isoleucine, and lysine. The conversion of aspartic acid to these other
amino acids begins with reduction of aspartic acid to its "semialdehyde," HO2CCH(NH2)CH2CHO.[2]
Asparagine is derived from aspartic acid via transamidation:
HO2CCH(NH2)CH2CO2H + GC(O)NH2 HO2CCH(NH2)CH2CONH2 + GC(O)OH
(where GC(O)NH2 and GC(O)OH are glutamine and glutamic acid, respectively)
2. Other biochemical roles
Aspartic acid is also a metabolite in the urea cycle and participates in gluconeogenesis. It carries reducing
equivalents in the malate-aspartate shuttle, which utilizes the ready interconversion of aspartate and
oxaloacetate, which is the oxidized (dehydrogenated) derivative of malic acid. Aspartic acid donates one
nitrogen atom in the biosynthesis of inositol, the precursor to the purine bases.
2.1. Neurotransmitter
Aspartate (the conjugate base of aspartic acid) stimulates NMDA receptors, though not as strongly as the
amino acid neurotransmitter glutamate does.[3] It serves as an excitatory neurotransmitter in the brain
and is an excitotoxin.
As a neurotransmitter, aspartic acid may provide resistance to fatigue and thus lead to endurance,
although the evidence to support this idea is not strong.
3. References
1. IUPAC-IUBMB Joint Commission on Biochemical Nomenclature. Nomenclature and Symbolism for
Amino Acids and Peptides. Recommendations on Organic & Biochemical Nomenclature, Symbols &
Terminology
etc.
2. Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York,
2000.
ISNB
1-57259-153-6.
3. Philip E. Chen, Matthew T. Geballe, Phillip J. Stansfeld, Alexander R. Johnston, Hongjie Yuan, Amanda
L. Jacob, James P. Snyder, Stephen F. Traynelis, and David J. A. Wyllie. 2005. Structural Features of the
Glutamate Binding Site in Recombinant NR1/NR2A N-Methyl-D-aspartate Receptors Determined by SiteDirected Mutagenesis and Molecular Modeling. Molecular Pharmacology. Volume 67, Pages 1470-1484.
4. Dunn, M. S.; Smart, B. W. DL-Aspartic Acid Organic Syntheses, Collected Volume 4, p.55
(1963).http://www.orgsyn.org/orgsyn/pdfs/CV4P0055.pdf
Cysteine
Cysteine is a naturally occurring, sulfur-containing amino acid that is a building block to most proteins.
Cysteine is unique among the twenty common amino acids because it contains a thiol group. Thiol groups
can undergo oxidation of a pair of cysteine residues is oxidised produces cystine, a disulfide-containing
derivative. This reaction is reversible. The disulphide bonds of cystine are crucial to defining the
structures of many proteins. Related to its redox behavoir, cysteine is incorporated into many proteins that
are redox-active, such as the antioxidant glutathione. Cysteine is named after cystine, which comes from
the Greek word kustis meaning bladder - cystine was first isolated from kidney stones.
Contents
1.
2.
3.
4.
5.
6.
7.
8.
8.1.
9. References
Biological
Dietary
Hangover
N-acetylcysteine
Reactions
functions
Biochemistry
sources
Production
Applications
Sheep
Remedy
(NAC)
1. Reactions
Like most thiols, cystein undergoes a variety of redox reactions. Oxidation by removal of hydrogen
("dehydrogenation") of cysteine produce the aforementioned disulfide cystine. More aggressive oxidants
produce sulphfinic or sulfonic acids.
The cysteine thiol group is also nucleophilic and, thus, can undergo addition and substitution reactions.
Thiol groups become much more reactive when they are ionised, and cysteine residues in proteins have
pKa values close to neutrality, so are often in their reactive thiolate form in the cell.[1]
The thiol group also has a high affinity for heavy metals, so that proteins containing cysteine will bind
metals such as mercury, lead and cadmium tightly.[2]
2. Biological functions
Due to this ability to undergo redox reactions, cysteine has antioxidant properties. Cysteine is an
important source of sulfur in human metabolism, and although it is classified as a non-essential amino
acid, cysteine may be essential for infants, the elderly, and individuals with certain metabolic disease or
who suffer from malabsorption syndromes.
Cysteine is an important precursor in the production of glutathione in the body and other organisms. The
systemic availability of oral glutathione (GSH) is negligible; the vast majority of it must be manufactured
intracellularly. Glutathione is a tripeptide antioxidant made up of the three amino acids cysteine, glycine
and glutamate. Glutamate and glycine are readily available in most North American diets, but the
availability of cysteine makes it be the rate-limiting substrate for the synthesis of glutathione within the
cell. It is the sulfhydryl (thiol) group (SH) of cysteine that serves as proton-donor and is responsible for the
biological activity of glutathione.[3]
The free amino acid cysteine (supplied supplementally by NAC) does not represent an ideal delivery
system to the cell. Cysteine is potentially toxic and is spontaneously catabolized in the gastrointestinal
tract and blood plasma. Conversely, cysteine absorbed during digestion as cystine (two cysteine
molecules linked by a disulfide bond) in the gastrointestinal tract is more stable than the free amino acid
cysteine. Cystine travels safely through the GI tract and blood plasma and is promptly reduced to the two
cysteine molecules upon cell entry.[3]
3. Biochemistry
Cysteine contains a thiol group, which can display nucleophilicity. Some important cysteine-derived
nucleophiles include ubiquitin ligases, which transfer ubiquitin to its pendant proteins, and caspases,
which engage in proteolysis in the apoptotic cycle. Inteins often function with the help of a catalytic
cysteine. These roles are typically limited to the intracellular milieu, where the environment is reducing,
and cysteine is not oxidized to cystine.
Cysteines play a valuable role by crosslinking proteins. This increases the molecular stability in the harsh
extracellular environment, and also functions to confer proteolytic resistance (since protein export is a
costly process, minimizing its necessity is advantageous). Intracellularly, disulfide bridges between
cysteines within a polypeptide support the protein's secondary structure. Insulin is an example of a protein
with cystine crosslinking, where two separate peptide chains are connected by a pair of disulfide bonds.
Protein Disulfide Isomerases catalyze the proper formation of disulfide bonds; the cell transfers
dehydroascorbic acid to the endoplasmic reticulum which oxidises the environment. In this environment,
cysteines are generally oxidized to cystine and no longer functions as a nucleophile.
4. Dietary sources
Cysteine can be found in eggs, meat, red peppers, garlic, onions, broccoli, brussel sprouts, oats, milk,
whey protein, and wheat germ. However, it is not classified as an essential amino acid, and can usually
be synthesized by the human body under normal physiological conditions if a sufficient quantity of
methionine is available.
5. Production
Currently the cheapest source of material from which food grade L-cysteine may be purified in high yield
is by hydrolysis of molecules in human hair. Other sources include feathers and pig bristles. The
companies producing cysteine by hydrolysis are located mainly in China. There is some debate whether
or not consuming L-cysteine derived from human hair constitutes cannibalism. Although many other
amino acids were accessible via fermentation for some years, L-Cysteine was unavailable until 2001
when a German company introduced a production route via fermentation (non-human, non-animal origin.)
A source of bonded cysteine (cystine) is undenatured bovine whey protein; this is the same form as that in
human breast milk.
6. Applications
Cysteine (mostly in the naturally occurring form L-cysteine) is a precursor in the food, pharmaceutical,
and personal care industries. One of the largest applications is the production of flavors. For example,
reacting cysteine with sugars in a Maillard reaction yields meat flavors.
L-cysteine is also used as a processing aid for baking. Small quantities (in the tens of ppm range) help to
soften the dough and thus reduce processing time.
In the field of personal care, cysteine is used for permanent wave applications predominantly in Asia.
Again the cysteine is used for breaking up the disulfide bonds in the hair's keratin.
Cysteine is a very popular target for site-directed labeling experiments to investigate biomolecular
structure and dynamics. Maleimides will selectively attach to cysteine using a covalent michael-addition.
Site-directed spin labeling for EPR also uses cysteine extensively.
In his 2006 doctoral thesis Ville Salaspuro proposes that:
The elevated aerodigestive tract cancer risk observed in smokers and drinkers may be the result of the
increased acetaldehyde exposure. Acetaldehyde produced in the oral cavity during ethanol challenge was
significantly decreased by a buccal L-cysteine -releasing tablet. Also smoking-derived acetaldehyde could
be totally removed by using a tablet containing L-cysteine.
In a 1994 report released by five top cigarette companies, cysteine is one of the 599 additives to
cigarettes. Its use or purpose, however, is unknown, like most cigarette additives.[4] Its inclusion in
cigarettes could offer two benefits: Acting as an expectorant, since smoking increases mucus production
in the lungs; and increasing the beneficial antioxidant glutathione (which is diminished in smokers).
7. Sheep
Cysteine is required by sheep in order to produce wool, however it is an essential amino-acid that cannot
be synthesised by the sheep and must be taken in as food from grass. This means that during drought
conditions sheep stop producing wool; however, transgenic sheep have been developed which can make
their own cysteine. A little concentration of cysteine is used to break the disulfide bonds during the
solublisation of recombinant protein preparation.
8. Hangover Remedy
Cysteine has been linked to aiding in the remedy of certain hangover symptoms. It directly counteracts
the poisonous effects of acetaldehyde, a particularly toxic by-product of alcohol in the human body.
Cysteine attracts the toxin, breaking it down into the non-toxic acetate, a substance similar to vinegar. The
actual effectiveness of consuming cysteine as part of a hangover remedy is unclear.[5]
8.1. N-acetylcysteine (NAC)
N-acetyl-L-cysteine (NAC) is a derivatives of cysteine wherein an acetyl group is attached to the nitrogen
atom. This compound is sometimes considered as a dietary supplement. NAC is often used as a cough
medicine as it breaks up the disulfide bonds in the mucus and thus liquefies it, making it easier to cough
up. NAC is also used as a dietary supplement as already indicated above, as well as a specific antidote in
cases of acetominophen overdose.
9. References
1. Bulaj G, Kortemme T, Goldenberg D (1998). "Ionization-reactivity relationships for cysteine thiols in
polypeptides.".Biochemistry 37
(25):
8965-72.
PMID
9636038.
2. Baker D, Czarnecki-Maulden G (1987). "Pharmacologic role of cysteine in ameliorating or exacerbating
mineral
toxicities.". J
Nutr 117
(6):
1003-10.
PMID
3298579.
3. http://www.ammunotec.com/glutathione.html
4. http://quitsmoking.about.com/cs/nicotineinhaler/a/cigingredients.htm
5. http://www.lef.org/protocols/prtcl-004.shtml
Glutamic Acid
Glutamic acid (Glu, E), also referred to as glutamate (the anion), is one of the 20 proteinogenic amino
acids. It is not among the essential amino acids.
Contents
1.
2.
2.1.
3.
3.1.
3.2.
3.3.
In
3.3.1.
4.
5.
6. References
In
As
brain
nonsynaptic
GABA
Sources
a
glutamatergic
and
Structure
Synthesis
Natural
Function
metabolism
neurotransmitter
signaling
circuits
precursor
absorption
Pharmacology
1. Structure
As its name indicates, it is acidic, with a carboxylic acid component to its side chain. Generally either the
amino group will be protonated or one or both of the carboxylic groups will be deprotonated. At neutral pH
all three groups are ionized and the species has a charge of -1. The pKa value for Glutamic acid is 4.1.
This means that at pH below this value it will be protonated (COOH) and at pH above this value it will be
deprotonated (COO-)
A three-letter designation for either Gln or Glu is Glxthis is often used in cases in which peptide
sequencing reactions may convert glutamine to glutamate (or vice versa), leaving the original identity of
the amino acid in doubt. The one-letter abbreviation is E for glutamic acid and Q for glutamine.
2. Synthesis
2.1. Natural
Reactants
Products
Enzymes
Glutamine + H2O
Glu + NH3
GLS, GLS2
NAcGlu + H2O
Glu + Acetate
(unknown)
-ketoglutarate + NADPH + NH4+
Glu + NADP+ + H2O
GLUD1, GLUD2
-ketoglutarate + -amino acid
Glu + -oxo acid
transaminase
1-pyrroline-5-carboxylate + NAD+ + H2O
Glu + NADH
ALDH4A1
N-formimino-L-glutamate + FH4
Glu + 5-formimino-FH4
FTCD
3. Function
3.1. In metabolism
Glutamate is a key molecule in cellular metabolism. In humans, dietary proteins are broken down by
digestion into amino acids, which serves as metabolic fuel for other functional roles in the body. A key
process in amino acid degradation is transamination, in which the amino group of an amino acid is
transferred to an -ketoacid, typically catalysed by a transaminase. The reaction can be generalised as
such:
R1-amino acid + R2--ketoacid R1--ketoacid + R2-amino acid
A very common -ketoacid is -ketoglutarate, an intermediate in the citric acid cycle. When ketoglutarate undergoes transamination, it always results in glutamate being formed as the corresponding
amino acid product. The resulting -ketoacid product is often a useful one as well, which can contribute
as fuel or as a substrate for further metabolism processes. Examples are as follows:
alanine + -ketoglutarate pyruvate + glutamate
aspartate + -ketoglutarate oxaloacetate + glutamate
Both pyruvate and oxaloacetate are key components of cellular metabolism, contributing as substrates or
intermediates in fundamental processes such as glycolysis, gluconeogenesis and also the citric acid
cycle.
Glutamate also plays an important role in the body's disposal of excess or waste nitrogen. Glutamate
undergoes deamination, an oxidative reaction catalysed by glutamate dehydrogenase, as follows:
glutamate + water + NAD+ -ketoglutarate + NADH + ammonia + H+
Ammonia (as ammonium) is then excreted predominantly as urea, synthesised in the liver.
Transamination can thus be linked to deamination, effectively allowing nitrogen from the amine groups of
amino acids to be removed, via glutamate as an intermediate, and finally excreted from the body in the
form of urea.
3.2. As a neurotransmitter
Glutamate is the most abundant fast excitatory neurotransmitter in the mammalian nervous system. At
chemical synapses, glutamate is stored in vesicles. Nerve impulses trigger release of glutamate from the
pre-synaptic cell. In the opposing post-synaptic cell, glutamate receptors, such as the NMDA receptor,
bind glutamate and are activated. Because of its role in synaptic plasticity, it is believed that glutamic acid
is involved in cognitive functions like learning and memory in the brain.
Glutamate transporters[3] are found in neuronal and glial membranes. They rapidly remove glutamate
from the extracellular space. In brain injury or disease, they can work in reverse and excess glutamate
can accumulate outside cells. This process causes calcium ions to enter cells via NMDA receptor
channels, leading to neuronal damage and eventual cell death, and is called excitotoxicity. The
mechanisms of cell death include:
Damage
to
mitochondria
from
excessively
high
intracellular
Ca2+[4].
Glu/Ca2+-mediated promotion of transcription factors for pro-apoptotic genes, or downregulation of
transcription factors for anti-apoptotic genes.
Excitotoxicity due to glutamate occurs as part of the ischemic cascade and is associated with stroke and
diseases like amyotrophic lateral sclerosis, lathyrism, and Alzheimer's disease.
Glutamic acid has been implicated in epileptic seizures. Microinjection of glutamic acid into neurons
produces spontaneous depolarisations around one second apart, and this firing pattern is similar to what
is known as paroxysmal depolarizing shift in epileptic attacks. This change in the resting membrane
potential at seizure foci could cause spontaneous opening of voltage activated calcium channels, leading
to glutamic acid release and further depolarization.
Experimental techniques to detect glutamate in intact cells include using a genetically-engineered
nanosensor[2]. The sensor is a fusion of a glutamate-binding protein and two fluorescent proteins. When
glutamate binds, the fluorescence of the sensor under ultraviolet light changes by resonance between the
two fluorophores. Introduction of the nanosensor into cells enables optical detection of the glutamate
concentration. Synthetic analogs of glutamic acid that can be activated by ultraviolet light have also been
described[6]. This method of rapidly uncaging by photostimulation is useful for mapping the connections
between neurons, and understanding synapse function.
3.3. In brain nonsynaptic glutamatergic signaling circuits
Extracellular glutamate in Drosophila brains has been found to regulate postsynaptic glutamate receptor
clustering, via a process involving receptor desensitization[7]. A gene expressed in glial cells actively
transports glutamate into the extracellular space[7], while in the nucleus accumbens stimulating group II
metabotropic glutamate receptors was found to reduce extracellular glutamate levels[8]. This raises the
possibility that this extracellular glutamate plays an "endocrine-like" role as part of a larger homeostatic
system.
3.3.1. GABA precursor
Glu also serves as the precursor for the synthesis of the inhibitory GABA in GABA-ergic neurons. This
reaction is catalyzed by GAD, glutamic acid decarboxylase, which is most abundant in cerebellum and
pancreas.
Stiff-man syndrome is a neurologic disorder caused by anti-GAD antibodies, leading to a decrease in
GABA synthesis and therefore, impaired motor function such as muscle stiffness and spasm. Since the
pancreas is also abundant for the enzyme GAD, a direct immunological destruction occurs in the
pancreas and the patients will have diabetes mellitus.
4. Sources and absorption
Glutamic acid is present in a wide variety of foods and is responsible for one of the five basic tastes of the
human sense of taste (umami), especially in its physiological form, the sodium salt of glutamate in a
neutral pH. Ninety-five percent of the dietary glutamate is metabolized by intestinal cells in a first pass [5].
Overall, glutamic acid is the single largest contributor to intestinal energy. As a source for umami, the
sodium salt of glutamic acid, monosodium glutamate (MSG) is used as a food additive to enhance the
flavor of foods, although an identical effect can be achieved by mixing and cooking together different
ingredients rich in this amino acid and other umami substances as well.
Another source of MSG is fruits, vegetables and nuts that have been sprayed with Auxigro. Auxigro is a
growth enhancer that contains 30% glutamic acid.
China-based Fufeng Group Limited is the largest producer of Glutamic Acid in the world, with capacity
increasing to 300,000 tons at the end of 2006 from 180,000 tons during 2006, putting them at 25 - 30% of
the chinese market. Meihua is the second largest Chinese producer. Together, the top five producers
have roughly 50% share in China. Chinese demand is roughly 1.1 million tons per year, while global
demand, including China, is 1.7 million tons per year.
5. Pharmacology
The drug phencyclidine (more commonly known as PCP) antagonizes glutamic acid non-competitively at
the NMDA receptor. For the same reasons, sub-anaesthetic doses of Ketamine have strong dissociative
and hallucinogenic effects. Glutamate does not easily pass the blood brain barrier, but: "glutamate flux
from plasma into brain is mediated by a high affinity transport system at the Blood-Brain Barrier" [1]. It can
also be converted into glutamine.
Glutamate transport and supply are obvious targets for the treatment of epilepsy, therefore. In particular
Glutamate Restriction Diets are now claiming success anecdotally, by limiting or eliminating intake of
wheat, peanut, soy and bean. No similar diets for schizophrenia are known.
6. References
1. Nelson DL and Cox MM. Lehninger Principles of Biochemistry, 4th edition.

2. Okumoto, S., et al. (2005). "Detection of glutamate release from neurons by genetically encoded
surface-displayed FRET nanosensors". Proceedings of the National Academy of Sciences U.S.A 102
(24):
8740-8745.
3. Molecular pharmacology of glutamate transporters, EAATs and VGLUTs. Brain Res Brain Res Rev.
2004
Jul;
45(3):250-65.
4. Delayed increase of Ca2+ influx elicited by glutamate: role in neuronal death. Mol Pharmacol. 1989
Jul;36(1):106-12.
5. Reeds, P.J., et al. (2000). "Intestinal glutamate metabolism". Journal of Nutrition 130 (4s): 978S-982S.
6. Corrie, J.E., et al. (1993). "Postsynaptic activation at the squid giant synapse by photolytic release of Lglutamate
from
a
'caged'
L-glutamate".
Journal
of
Physiology
465
(Jun):
1-8.
7. Augustin H, Grosjean Y, Chen K, Sheng Q, Featherstone DE (2007). "Nonvesicular release of
glutamate by glial xCT transporters suppresses glutamate receptor clustering in vivo". Journal of
Neuroscience
27
(1):
111-123.
8. Zheng Xi, Baker DA, Shen H, Carson DS, Kalivas PW (2002). "Group II metabotropic glutamate
receptors modulate extracellular glutamate in the nucleus accumbens". Journal of Pharmacology and
Experimental Therapeutics 300 (1): 162-171.
Glutamine
Glutamine (Gln, Q) is one of the 20 amino acids encoded by the standard genetic code. Its side chain is
an amide; it is formed by replacing a side-chain hydroxyl of glutamic acid with an amine functional group.
1. Biochemistry
1.1. Formation and Nomenclature
Glutamine is genetically coded for by the RNA codons CAA and CAG. Glutamine's three-letter
abbreviation is Gln, and its one-letter abbreviation is Q. A three-letter designation for either glutamine or
glutamic acid is Glx (one-letter abbreviation: Z).
Like other amino acids, glutamine is biochemically important as a constituent of proteins. Glutamine is
also crucial in nitrogen metabolism. Ammonia (formed by nitrogen fixation) is assimilated into organic
compounds by converting glutamic acid to glutamine. The enzyme that accomplishes this is called
glutamine synthetase. Glutamine can, hence, be used as a nitrogen donor in the biosynthesis of many
compounds, including other amino acids, purines, and pyrimidines.
Artificial glutamine synthesis was first reported in 1933 in the Bergmann-Zervas carbobenzoxy method [1]
2. Nutrition
2.1. Occurrences in Nature
Glutamine is found in foods high in proteins, such as fish, red meat, beans, and dairy products.
2.2. Use
Glutamine is a supplement that is used in weightlifting, bodybuilding, endurance and other sports, as well
as by those who suffer from muscular cramps or painparticularly elderly people. The main use of
glutamine within the diet of either group is as a means of replenishing the body's supply of amino acids
that
have
been
used
during
exercise
or
everyday
activities.
Studies which are looking into problems with excessive consumption of glutamine thus far have proved
inconclusive. There is a belief that a serving size greater than five grams converts the remainder into
ammonia. This is a classic instance of a practical belief in healthfood supplementation that too much of a
good substance will incur the opposite effect. Normal supplementation is healthy mainly because
glutamine is helpful after prolonged periods of exercise (for example, a workout or exercise in which
amino acids are required for use) and replenishes amino acid supply; this being the main reason
glutamine is recommended during fasting or for people who suffer from physical trauma, immune
deficiencies, or cancer.[2] A secondary benefit to bettering body immunity is fortification of the intestinal
tract, responsible for roughly 70% of the body's immunity.
2.3. Aiding gastrointestinal function
There have been several recent studies into the effects of glutamine and what properties it possesses,
and, there is now a significant body of evidence that links glutamine-enriched diets with intestinal effects;
aiding maintenance of gut barrier function, intestinal cell proliferation and differentiation, as well as
generally reducing septic morbidity and the symptoms of Irritable Bowel Syndrome. The reason for such
"cleansing" properties is thought to stem from the fact that the intestinal extraction rate of glutamine is
higher than that for other amino acids, and is therefore thought to be the most viable option when
attempting to alleviate conditions relating to the gastrointestinal tract. [3]
These conditions were discovered after comparing plasma concentration within the gut between
glutamine-enriched and non glutamine-enriched diets. However, even though glutamine is thought to
have "cleansing" properties and effects, it is unknown to what extent glutamine has clinical benefits, due
to the varied concentrations of glutamine in varieties of food. [3]
2.4. Aiding recovery after surgery
It is also known that glutamine has various effects in reducing healing time after operations. Hospital
waiting times after abdominal surgery are reduced by providing parenteral nutrition regimens containing
amounts of glutamine to patients. Clinical trials have revealed that patients on supplementation regimens
containing glutamine have improved nitrogen balances, generation of cysteinyl-leukotrienes from
polymorphonuclear neutrophil granulocytes and improved lymphocyte recovery and intestinal permeability
(in postoperative patients) - in comparison to those who had no glutamine within their dietary regime; all
without any side-effects. [4]
3. References
1. Bergmann, M., Zervas, L., and Salzmann, L., Ber. them. Ges., 99, 1233 (1933).
2. Glutamine
used
for
the
Immune
System
and
Cancer.
3. Boza J.J., Dangin M., Moennoz D., Montigon F., Vuichoud J., Jarret A., Pouteau E., Gremaud G.,
Oguey-Araymon S., Courtois D., Woupeyi A., Finot P.A. and Ballevre O. Free and protein-bound
glutamine have identical splanchnic extraction in healthy human volunteers. Am J Physiol Gastrointest
Liver
Physiol.
2001
Jul;
281(1):
G267-74.
4. Morlion B.J., Stehle P., Wachtler P., Siedhoff H.P., Koller M., Konig W., Furst P., Puchstein C. Total
parenteral nutrition with glutamine dipeptide after major abdominal surgery. Ann Surg. 1998 Feb; 227(2):
302-8.
Glycine
Glycine is the organic compound with the formula HO2CCH2NH2. It is one of the 20 amino acids
commonly found in animal proteins. Its three letter code is gly, its one letter code is G, and its codons are
GGU, GGC, GGA and GGG.[1] Because of its structural simplicity, this compact amino acid tends to be
evolutionarily conserved in, for example, cytochrome c, myoglobin, and hemoglobin. Glycine is the unique
amino acid that is not optically active. Most proteins contain only small quantities of glycine. A notable
exception is collagen, which contains about one-third glycine.
1. Biosynthesis
Glycine is not essential to the human diet, since it is synthesized in the body. It is biosynthesized from the
amino acid serine. The enzyme serine hydroxymethyl transferase catalyses this transformation:[2]
HO2CCH(NH2)CH2OH + H2folate HO2CCH2NH2 + CH2-folate + H2O
2. Physiological function
2.1. As a biosynthetic intermediate
Glycine is a building block to numerous species. Aminolevulinic acid, the key precursor to porphyrins is
biosynthesized from glycine and succinoyl coenzyme A. Glycine provides the central C2N subunit of all
purines.[2]
2.2. As a neurotransmitter
Glycine is an inhibitory neurotransmitter in the central nervous system, especially in the spinal cord,
brainstem, and retina. When glycine receptors are activated, chloride enters the neuron via ionotropic
receptors, causing an Inhibitory postsynaptic potential (IPSP). Strychnine is an antagonist at ionotropic
glycine receptors. Glycine is a required co-agonist along with glutamate for NMDA receptors. In contrast
to the inhibitory role of glycine in the spinal cord, this behaviour is facilitated at the (NMDA) glutaminergic
receptors which are excitatory. The LD50 of glycine is 7930 mg/kg in rats (oral),[3] and it usually causes
death by hyperexcitability.
3. Presence in the interstellar medium
In 1994 a team of astronomers at the University of Illinois, led by Lewis Snyder, claimed that they had
found the glycine molecule in space. It turned out that, with further analysis, this claim could not be
confirmed. Nine years later, in 2003, Yi-Jehng Kuan from National Taiwan Normal University and Steve
Charnley claimed that they detected interstellar glycine toward three sources in the interstellar medium
[1]. They claimed to have identified 27 spectral lines of glycine utilizing a radio telescope. According to
computer simulations and lab-based experiments, glycine was probably formed when ices containing
simple organic molecules were exposed to ultraviolet light [4].
In October 2004, Snyder and collaborators reinvestigated the glycine claim in Kuan et al. (2003). In a
rigorous attempt to confirm the detection, Snyder showed that glycine was not detected in any of the three
claimed sources [2].
Should the glycine claim be substantiated, it does not prove that life exists outside the Earth, but certainly
makes that possibility more plausible by showing that amino acids can be formed in the interstellar
medium. The finding would also indirectly support the idea of panspermia, the theory that life was brought
to Earth from space. As in Miller-Urey experiment, it should be noted that glycine is but the simplest of
amino acids.
4. References
1. Kuan YJ, Charnley SB, Huang HC, et al. (2003) Interstellar glycine. ASTROPHYS J 593 (2): 848-867
2. Snyder LE, Lovas FJ, Hollis JM, et al. (2005) A rigorous attempt to verify interstellar glycine.
ASTROPHYS
J
619
(2):
914-930
3. Safety (MSDS) data for glycine. The Physical and Theoretical Chemistry Laboratory Oxford University
(2005).
Retrieved
on
2006-11-01.
4. Dawson, R.M.C., Elliott, D.C., Elliott, W.H., and Jones, K.M., Data for Biochemical Research (3rd
edition),
pp.
1-31
(1986)
5. www.newscientist.com
4. External links
Glycine
Glycine
cleavage
system
Histidine
Histidine (His, H) is one of the 20 most common natural amino acids present in proteins. In the nutritional
sense, in humans, histidine is considered an essential amino acid, but mostly only in children.
1. Chemical properties
The imidazole side chains and the relatively neutral pKa of histidine (ca 6.0) mean that relatively small
shifts in cellular pH will change its charge. For this reason, this amino acid side chain finds its way into
considerable use as a co-ordinating ligand in metalloproteins, and also as a catalytic site in certain
enzymes. The imidazole side chain has two nitrogens with different properties: One is bound to hydrogen
and donates its lone pair to the aromatic ring and as such is slighty acidic, whereas the other one donates
only one electron pair to the ring so it has a free lone pair and is basic. These properties are exploited in
different ways in proteins. In catalytic triads, the basic nitrogen of histidine is used to abstract a proton
from serine, threonine or cysteine to activate it as a nucleophile. In a histidine proton shuttle, histidine is
used to quickly shuttle protons, it can do this by abstracting a proton with its basic nitrogen to make a
positively-charged intermediate and then use another molecule, a buffer, to extract the proton from its
acidic nitrogen. In carbonic anhydrases, a histidine proton shuttle is utilized to rapidly shuttle protons
away from a zinc-bound water molecule to quickly regenerate the active form of the enzyme.
2. Metabolism
The amino acid is a precursor for histamine and carnosine biosynthesis.
Conversion of histidine to histamine by histidine decarboxylase

The enzyme histidine ammonia-lyase converts histidine into ammonia and urocanic acid. A deficiency in
this enzyme is present in the rare metabolic disorder histidinemia.
3. Sources
Histidine is found in fruits such as bananas and grapes, meat and poultry, and milk and milk products. It is
also found in root vegetables and all green vegetables, though in lesser quantities.
4. Forms
There are two enantiomers: D-histidine and L-histidine.
5. History
Histidine was first isolated in 1896 by German physician Albrecht Kossel.
6. External links
Histidine
Histidine
Histidine catabolism
biosynthesis
biosynthesis
(early
(later
stages)
stages)
Isoleucine
Isoleucine is an -amino acid with the chemical formula HO2CCH(NH2)CH(CH3)CH2CH3. Its three letter
code is ILE and its one letter code is I. It is an essential amino acid, which means that humans cannot
synthesise it, so it must be part of our diet. With a hydrocarbon side chain, Isoleucine is classified as a
hydrophobic amino acid.
Together with threonine, isoleucine is one of two common amino acids that has a chiral side chain. Four
stereoisomers of isoleucine are possible, including two possible diastereomers of L-isoleucine. However,
isoleucine present in nature exists in one enantiomeric form, (2S,3S)-2-amino-3-methylpentanoic acid.
1. Biosynthesis
As an essential amino acid, isoleucine is not synthesized in animals, hence it must be ingested, usually
as a component of proteins. In plants and microorganisms, it is synthesized via several steps starting
from pyruvic acid and alpha-ketoglutarate. Enzymes involved in this biosynthesis include:[1]
acetohydroxy
valine aminotransferase
acetolactate
synthase
isomeroreductase
dehydratase
acid
dihydroxyacid
2. Isomers of isoleucine
Forms of Isoleucine
Common
name:
isoleucine
Dallo-DL-isoleucine DL-isoleucine
isoleucine
isoleucine
Synonyms:
(R)L(+)Isoleucine Isoleucine
(R*,R*)isoleucine
PubChem:
CID 791 CID 94206 CID 6306
CID 76551
EINECS
number:
207-139-8 206-269-2 200-798-2
CAS number: 443-79-8 319-78-8
73-32-5
allo-Lisoleucine
allo-DLisoleucine
alloisoleucine
216-143-9
216-142-3
221-464-2
1509-35-9
1509-34-8
3107-04-8
3. Synthesis
Isoleucine can be synthesized in a multistep procedure starting from 2-bromobutane and diethylmalonate.
[2] Synthetic isoleucine was originally reported in 1905.[3]
4. Dietary aspects
Rich sources of isoleucine are eggs, chicken, pork, mutton, pulses, soya beans, cottage cheese, milk,
piyal seeds, cashew nuts, and cereal grains.
5. References
2000.
2.
Marvel,
C.
S.
dl-Isoleucine
Organic
Syntheses,
Collected
Volume
3,
p.495
3. Bouveault and Locquin, Compt. rend., 141, 115 (1905).
6. External links
Isoleucine and valine biosynthesis
Leucine
Leucine is an -amino acid with the chemical formula HO2CCH(NH2)CH2CH(CH3)2. Its three letter code
is leu, its one letter code is L, and its codons are UUA, UUG, CUU, and CUC. It is an essential amino
acid, which means that humans cannot synthesise it. With a hydrocarbon side chain, leucine is classified
as a hydrophobic amino acid. It is an isomer of isoleucine.
1. Biosynthesis
As an essential amino acid, leucine is not synthesized in animals, hence it must be ingested, usually as a
component of proteins. It is synthesized in plants and microorganisms via several steps starting from
pyruvic acid. The initial part of the pathway also leads to valine. The intermediate -ketovalerate is
converted to -isopropylmalate and then -isopropylmalate, which is dehydrogenated to ketoisocaproate, which in the final step undergoes reductive amination. Enzymes involved in a typical
biosynthesis include:[1]
acetolactate
acetohydroxy
dihydroxyacid
-isopropylmalate
-isopropylmalate
leucine aminotransferase
2. Dietary aspects
acid
synthase
isomeroreductase
dehydratase
synthase
isomerase
Major food sources of leucine include whole grains, milk products, eggs (~1 g/100g), pork, beef, chicken,
pulses (such as soybeans (~3 g/100g), chick peas and lentils) and leaf vegetables.
3. References
2000.
4. External links
Leucine
Leucine
content
Leucine
prevents
muscle
Leucine helps regulate appetite in rats
in
loss
in
biosynthesis
food
rats
Lysine
Lysine is an -amino acid with the chemical formula HO2CCH(NH2)(CH2)4NH2. Its three letter code is
Lys, its one letter code is K, and its codons are AAA and AAG. This amino acid is essential amino acid,
which means that humans cannot synthesise it. Lysine is a basic, as are arginine and histidine. The amino group often participates in hydrogen bonding and as a general base in catalysis.
Common posttranslational modifications include methylation of the e-amino group, giving methyl-,
dimethyl-, and trimethyllysine. The latter occurs in calmodulin. Other posttranslational modifications
include acetylation. Collagen contains hydroxylysine which is derived from lysine by lysyl hydroxylase. OGlycosylation of lysine residues in the endoplasmic reticulum or Golgi apparatus is used to mark certain
proteins for secretion from the cell.
1. Biosynthesis
As an essential amino acid, lysine is not synthesized in animals, hence it must be ingested as lysine or
lysine-containing proteins. In plants and microorganisms, it is synthesized from aspartic acid, which is first
converted to -aspartyl-semialdehyde. Cyclization gives dihydropicolinate, which is reduced to 1piperidine-2,6-dicarboxylate. Ring-opening of this heterocycle gives a series of derivatives of pimelic acid,
ultimately affording lysine. Enzymes involves in this biosynthesis include:[1]
-aspartate
semialdehyde
dihydropicolinate
1-piperdine-2,6-dicarboxylate
N-succinyl-2-amino-6ketopimelate
succinyl
diaminopimelate
aspartokinase
dehydrogenase
synthase
dehydrogenase
synthase
aminotransferase

succinyl
diaminopimelate decarboxylase
diaminopimelate
diaminopimelate
desuccinylase
epimerase
2. Metabolism
Lysine is metabolised in mammals to give acetyl-CoA, via an initial transamination with -ketoglutarate.
The bacterial degradation of lysine yields cadaverine by decarboxylation.
3. Synthesis
Synthetic, racemic lysine has long been known.[2] A practical synthesis starts from caprolactam.[3]
4. Dietary sources
The human nutritional requirement is 11.5 g daily. Used as a dietary supplement. It is the limiting amino
acid in all cereal grains, but is plentiful in all pulses (legumes). Fish are also quite rich in lysine. Plants
that contain significant amounts of lysine include:[citation needed]
Buffalo
Gourd
(10,13033,000
ppm)
in
seed
Berro,
Watercress
(1,34026,800
ppm)
in
herb.
Soybean
(24,29026,560
ppm)
in
seed.
Carob,
Locust
Bean,
St.John's-Bread
(26,320
ppm)
in
seed;
Common Bean (Black Bean, Dwarf Bean, Field Bean, Flageolet Bean, French Bean, Garden Bean,
Green Bean, Haricot, Haricot Bean, Haricot Vert, Kidney Bean, Navy Bean, Pop Bean, Popping Bean,
Snap
Bean,
String
Bean,
Wax
Bean)
(2,39025,700
ppm)
in
sprout
seedling;
Ben Nut, Benzolive Tree, Jacinto (Sp.), Moringa (aka Drumstick Tree, Horseradish Tree, Ben Oil Tree),
West
Indian
Ben
(5,37025,165
ppm)
in
shoot.
Lentil
(7,12023,735
ppm)
in
sprout
seedling.
Asparagus Pea, Winged Bean (aka Goa Bean) (21,36023,304 ppm) in seed.
Fat
Hen
(3,54022,550
ppm)
in
seed.
Lentil
(19,57022,035
ppm)
in
seed.
White
Lupin
(19,33021,585
ppm)
in
seed.
Black Caraway, Black Cumin, Fennel-Flower, Nutmeg-Flower, Roman Coriander (16,20020,700 ppm)
in
seed.
Spinach
(1,74020,664
ppm).
Amaranth, Quinoa
5. Properties
L-Lysine is a necessary building block for all protein in the body. L-Lysine plays a major role in calcium
absorption; building muscle protein; recovering from surgery or sports injuries; and the body's production
of hormones, enzymes, and antibodies.
6. Clinical significance
It has been suggested that lysine may be beneficial for those with herpes simplex infections.[4] However,
more research is needed to fully substantiate this claim. For more information, refer to Herpes simplex Lysine.
7. References
2000.
ISBN
1-57259-153-6.
2. Braun, J. V. Synthese des inaktiven Lysins aus Piperidin" Berichte der deutschen chemischen
Gesellschaft
1909,
Volume
42,
p
839-846.
3. Eck, J. C.; Marvel, C. S. dl-Lysine Hydrochlorides Organic Syntheses, Collected Volume 2, p.374
4. Griffith RS, Norins AL, Kagan C. (1978). "A multicentered study of lysine therapy in Herpes simplex
infection". Dermatologica. 156 (5): 257-267.
8. External links
Lysine
Lysine
Lysine
L-Lysine
biosynthesis
biosynthesis
(early
(later
stages)
stages)
catabolism
Methionine
Methionine is an -amino acid with the chemical formula HO2CCH(NH2)CH2CH2SCH3. This essential is
classified as nonpolar. Together with cysteine, methionine is one of two sulfur-containing proteinogenic
amino acids. Its derivative S-adenosyl methionine (SAM) serves as a methyl donor. Methionine plays a
role in the biosynthesis of cysteine, carnitine, and taurine (by the transsulfuration pathway), lecithin
production, the synthesis of phosphatidylcholine, and other phospholipids. Improper conversion of
methionine can lead to atherosclerosis.
Methionine is one of only two amino acids encoded by a single codon (AUG) in the standard genetic code
(tryptophan, encoded by UGG, is the other). The codon AUG is also significant, in that it carries the "Start"
message for a ribosome to begin protein translation from mRNA. As a consequence, methionine is
incorporated into the N-terminal position of all proteins in eukaryotes and archaea during translation,
although it is usually removed by post-translational modification.
1. Biosynthesis
As an essential amino acid, methionine is not synthesized in humans, hence we must ingest methionine
or methionine-containing proteins. In plants and microorganisms, methionine is synthesized via a pathway
that uses both aspartic acid and cysteine. First, aspartic acid is converted via -aspartyl-semialdehyde
into homoserine, introducing the pair of contiguous methylene groups. Homoserine converts to O-succinyl
homoserine, which then reacts with cysteine to produce cystathionine, which is cleaved to yield
homocysteine. Subsequent methylation of the thiol group by folates affords methionine. Both
cystathionine--synthase and cystathionine--lyase require Pyridoxyl-5'-phosphate as a cofactor, whereas
homocysteine methyltransferase requires Vitamin B12 as a cofactor.[1]
Enzymes involved in methionine biosynthesis:

aspartokinase
-aspartate
semialdehyde
dehydrogenase
homoserine
dehydrogenase
homoserine
acyltransferase
cystathionine--synthase
cystathionine--lyase
methionine synthase (in mammals, this step is performed by homocysteine methyltransferase)
2. Other biochemical pathways

Although mammals cannot synthesize methionine, they can still utilize it in a variety of biochemical
pathways:
Methionine is converted to S-adenosylmethionine (SAM) by (1) methionine adenosyltransferase. SAM

serves as a methyl-donor in many (2) methyltransferase reactions and is converted to Sadenosylhomocysteine (SAH). (3) adenosylhomocysteinase converts SAH to homocysteine.
There are two fates of homocysteine.
First, methionine can be regenerated from homocysteine via (4) methionine synthase. It can also be
remethylated using glycine betaine (NNN-trimethyl glycine) to methionine via the enzyme Betainehomocysteine methyltransferase (E.C.2.1.1.5, BHMT). BHMT makes up to 1.5% of all the soluble protein
of the liver, and recent evidence suggests that it may have a greater influence on methionine and
homocysteine homeostasis than Methionine sythase.
Alternatively, homocysteine can be converted to cysteine. (5) cystathionine--synthase (a PLPdependent enzyme) combines homocysteine and serine to produce cystathionine. Instead of degrading
cystathionine via cystathionine--lyase as in the biosynthetic pathway, cystathionine is broken down to
cysteine and -ketobutyrate via (6) cystathionine--lyase. (7) -ketoacid dehydrogenase converts ketobutyrate to propionyl-CoA, which is metabolized to succinyl-CoA in a three-step process (see
propionyl-CoA for pathway).
Fates of methionine
3. Synthesis
Racemic
methionine
can
be
synthesized
from
diethyl
sodium
phthalimidomalonate,
(C6H4(CO)2NC(CO2Et)2), by alkylation with chloroethylmethylsulfide, ClCH2CH2SCH3 followed by
hydrolysis and decarboxylation.[2]
4. Dietary aspects
High levels of methionine can be found in sesame seeds, Brazil nuts, fish, meat, and some seeds. Most
fruit and vegetables contain very little, although peppers and spinach are the best sources.
5. References
2000. ISBN 1-57259-153-6.
2. Barger, G.; Weichselbaum, T. E. dl-Methionine Organic Syntheses, Collected Volume 2, p.384

(1943).http://www.orgsyn.org/orgsyn/pdfs/CV2P0384.pdf.
Phenylanine
Phenyl alanine is an -amino acid with the formula HO2CCH(NH2)CH2C6H5. This essential amino acid is
classified as nonpolar because of the hydrophobic nature of the benyl side chain. The codons for Lphenylalanine are UUU and UUC. It is a white, powdery solid. L-Phenylalanine (LPA) is an electricallyneutral amino acid, one of the twenty common amino acids used to biochemically form proteins, coded for
by DNA.
Contents
1.
2.
2.1.
3.
4.
5.
6.
7. External links
Other
biological
Dietary
D-
and
Biosynthesis
roles
Phenylketonuria
aspects
DL-phenylalanine
History
References
1. Biosynthesis
Phenylalanine cannot be made by animals, which have to obtain it from their diet. It is produced by plants
and most microorganisms from prephenate, an intermediate on the shikimate pathway.[1]
Prephenate is decarboxylated with loss of the hydroxyl group to give phenylpyruvate. This species is
transaminated using glutamate as the nitrogen source to give phenylalanine and -ketoglutarate.
2. Other biological roles
L-phenylalanine can also be converted into L-tyrosine, another one of the DNA-encoded amino acids. Ltyrosine in turn is converted into L-DOPA, which is further converted into dopamine, norepinephrine
(noradrenaline), and epinephrine (adrenaline) (the latter three are known as the catecholamines).
Phenylalanine uses the same active transport channel as tryptophan to cross the blood-brain barrier, and,
in large quantities, interferes with the production of serotonin.
Lignin is derived from phenylalanine and from tyrosine. Phenylalanine is converted to cinnamic acid by
the enzyme phenylalanine ammonia lyase.[1]
2.1. Phenylketonuria
The genetic disorder phenylketonuria (PKU) is the inability to metabolize phenylalanine. Individuals with
this disorder are known as "phenylketonurics" and must abstain from consumption of phenylalanine. This
dietary restriction also applies to pregnant women with hyperphenylalanine (high levels of phenylalanine
in blood) because they do not properly metabolize the amino acid phenylalanine. Phenylalanine is present
in many sugarless gums, Monster Munch crisps, sugarless soft drinks (such as Diet Coke, and Diet
Pepsi), some forms of Lipton Tea, Icebreakers Mints, Clear Splash flavored water, and a number of other
food products, all of which must be labeled: "Phenylketonurics: Contains phenylalanine." Phenylalanine
itself is not present in the food. Rather, the artificial sweetener aspartame sold under the names "Equal"
and "NutraSweet" contain Aspartame, an ester that is hydrolyzed in the body to give phenylalanine,
aspartic acid, and methanol (wood alcohol). Thus, aspartame should is problematic for persons with PKU.
The amounts produced by aspartame pose a risk however, as far larger quantities of the amino acid
would be obtained through consuming normal protein. Interestingly, the macaque genome was recently
sequenced and it was found that macaques naturally have a mutation that is found in humans who have
PKU.[1]
3. Dietary aspects
Phenylalanine is contained in most protein-rich foods. Especially good sources are dairy products (curd,
milk, cottage cheese), avocados, pulses and legumes (particularly peanuts and lima beans), nuts
(pistachios, almonds), seeds (piyal seeds), leafy vegetables, whole grains, poultry, fish, other seafoods,
and some diet beverages.
4. D- and DL-phenylalanine
D-phenylalanine (DPA) either as a single enantiomer or as a component of the racemic mixture is
available through conventional organic synthesis. It does not participate in protein biosynthesis although it
is found in proteins, in small amounts, particularly aged proteins and food proteins that have been
processed. The biological functions of D-amino acids remain unclear. Some D-amino acids, such as Dphenylalanine, may have pharmacologic activity.
DL-Phenylalanine is marketed as a nutritional supplement for its putative analgesic and antidepressant
activities. The putative analgesic activity of DL-phenylalanine may be explained by the possible blockage
by D-phenylalanine of enkephalin degradation by the enzyme carboxypeptidase A. The mechanism of DLphenylalanine's putative antidepressant activity may be accounted for by the precursor role of Lphenylalanine in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain
norepinephrine and dopamine levels are thought to be associated with antidepressant effects.
D-phenylalanine is absorbed from the small intestine, following ingestion, and transported to the liver via
the portal circulation. A fraction of D-phenylalanine appears to be converted to L-phenylalanine. Dphenylalanine is distributed to the various tissues of the body via the systemic circulation. Dphenylalanine appears to cross the blood-brain barrier with less efficiency than L-phenylalanine. A fraction
of an ingested dose of D-phenylalanine is excreted in the urine.
5. History
The genetic codon for phenylalanine was the first to be discovered. Marshall W. Nirenberg discovered
that insertion of m-RNA made up of multiple uracil repeats into E. coli, the bacterium produced a new
protein, made up solely of repeated phenylalanine amino acids.
6. References
2000. ISBN 1-57259-153-6.
7. External links
Phenylalanine
and
Nitrogen
Order's
Molecule
DL-phenylalanine versus imipramine in depression
tyrosine
of
the
biosynthesis
Week
Proline
L-Proline is one of the twenty proteinogenic units which are used in living organisms as the building
blocks of proteins. The other nineteen units are all primary amino acids, but due to the cyclic binding of
the three-carbon side chain to the nitrogen of the backbone, proline lacks a primary amine group (NH2).
The nitrogen in proline is properly referred to as a secondary amine. Proline is sometimes called an imino
acid, although the IUPAC definition of an imine requires a carbon-nitrogen double bond. In biological
terminology, however, the category "amino acids" is generally taken to include proline.
1. Structural properties
The distinctive cyclic structure of proline's side chain locks its backbone dihedral angle at approximately
-75, giving proline an exceptional conformational rigidity compared to other amino acids. Hence, proline
loses less conformational entropy upon folding, which may account for its higher prevalence in the
proteins of thermophilic organisms. Proline acts as a structural disruptor in the middle of regular
secondary structure elements such as alpha helices and beta sheets; however, proline is commonly found
as the first residue of an alpha helix and also in the edge strands of beta sheets. Proline is also commonly
found in turns, which may account for the curious fact that proline is usually solvent-exposed, despite
having a completely aliphatic side chain. Because proline lacks a hydrogen on the amide group, it cannot
act as a hydrogen bond donor, only as a hydrogen bond acceptor.
Multiple prolines and/or hydroxyprolines in a row can create a polyproline helix, the predominant
secondary structure in collagen. The hydroxylation of proline by prolyl hydroxylase (or other additions of
electron-withdrawing substituents such as fluorine) increases the conformational stability of collagen
significantly. Hence, the hydroxylation of proline is a critical biochemical process for maintaining the
connective tissue of higher organisms. Severe diseases such as scurvy can result from defects in this
hydroxylation, e.g., mutations in the enzyme prolyl hydroxylase or lack of the necessary ascorbate
(vitamin C) cofactor.
Sequences of proline and 2-aminoisobutyric acid (Aib) also form a helical turn structure.
2. Cis-trans isomerization
Peptide bonds to proline and other N-substituted amino acids (such as sarcosine) are able to populate
both the cis and trans isomers. Most peptide bonds prefer overwhelmingly to adopt the trans isomer
(typically 99.9% under unstrained conditions), chiefly because the amide hydrogen (trans isomer) offers
less steric repulsion to the preceding C atom than does the following C atom (cis isomer). By contrast,
the cis and trans isomers of the X-Pro peptide bond are nearly isosteric (i.e., equally bad energetically);
the C (cis isomer) and C atoms (trans isomer) of proline are roughly equivalent sterically. Hence, the
fraction of X-Pro peptide bonds in the cis isomer under unstrained conditions ranges from 10-40%; the
fraction depends slightly on the preceding amino acid X, with aromatic residues favoring the cis isomer
slightly.
Cis-trans proline isomerization is a very slow process that can impede the progress of protein folding by
trapping one or more prolines crucial for folding in the nonnative isomer, especially when the native
isomer is the rarer cis. All organisms possess prolyl isomerase enzymes to catalyze this isomerization,
and some bacteria have specialized prolyl isomerases associated with the ribosome. However, not all
prolines are essential for folding, and protein folding may proceed at a normal rate despite having nonnative isomers of many X-Pro peptide bonds.
3. Synthesis and usage
Proline is biosynthetically derived from the amino acid L-glutamate and its direct precursor is the real
imino acid (S)-1-pyrroline-5-carboxylate (P5C).
Proline and its derivatives are often used as asymmetric catalysts in organic reactions. The CBS
reduction or proline catalysed aldol condensation are prominent examples.
Proline has a sweet flavor with a distinct aftertaste. Proline also causes slight irritation to the tongue like
Sichuan Pepper.
For unknown reasons, L-proline is used as an ingredient in energy drinks such as "Sobe power fruit
punch".
4. External links
Proline
Proline biosynthesis 2
biosynthesis
5. References
Balbach J, Schmid FX. (2000). Proline isomerization and its catalysis in protein folding. In Mechanisms
of Protein Folding 2nd ed. Editor RH Pain. Oxford University Press.
Serine
Serine is the organic compound with the formula HO2CCH(NH2)CH2OH. It is one of the 20 amino acids
commonly found in animal proteins. Its three letter code is ser, its one letter code is S, and its codons are
AGU and AGC.[1] Only the L-stereoisomer appears in mammalian protein. It is not essential to the human
diet, since it is synthesized in the body from other metabolites, including glycine. Serine was first obtained
from silk protein, a particularly rich source, in 1865. Its name is derived from the Latin for silk, sericum.
Serine's structure was established in 1902. The hydroxyl group attached makes it a polar amino acid.
1. Biosynthesis
The synthesis of serine starts with the oxidation of 3-phosphoglycerate forming 3phosphohydroxypyruvate and NADH. Reductive amination of this ketone followed by hydrolysis affords
serine. Serine hydroxymethyltransferase catalyzes the reversible, simultaneous conversions of L-serine to
glycine (retro-aldol cleavage) and 5,6,7,8-tetrahydrofolate to 5,10-methylenetetrahydrofolate (hydrolysis).
[2]
2. Function
2.1. Metabolic
Serine is important in metabolism in that it participates in the biosynthesis of purines and pyrimidines. It is
also the precursor to several amino acids, including glycine, cysteine, tryptophan (in bacteria). It is also
the precursor to numerous of other metabolites, including sphingolipids. Serine is also a precursor to
folate which is the principal donor of one carbon fragments in biosynthesis.
2.2. Structural
Serine plays an important role in the catalytic function of many enzymes. It has been shown to occur in
the active sites of chymotrypsin, trypsin, and many other enzymes. The so-called nerve gases and many
substances used in insecticides have been shown to act by combining with a residue of serine in the
active site of acetylcholine esterase, inhibiting the enzyme completely. Without the esterase activity that
usually destroys acetylcholine as soon as it performs its function, dangerously high levels of this
neurotransmitter build up, quickly resulting in convulsions and death.
As a constituent (residue) of proteins, its side chain can undergo O-linked glycosylation. This might be
important in explaining some of the devastating consequences of diabetes. It is one of three amino acid
residues that are commonly phosphorylated by kinases during cell signaling in eukaryotes.
Phosphorylated serine residues are often referred to as phosphoserine. Serine proteases are a common
type of protease.
2.3. Signaling
D-serine, synthesized by serine racemase from L-serine, serves as a neuronal signaling molecule by
activating NMDA receptors in the brain.
3. Chemical Synthesis
Serine is prepared from methyl acrylate.[3]
4. References
1. IUPAC-IUBMB Joint Commission on Biochemical Nomenclature. Nomenclature and Symbolism for
Amino Acids and Peptides. Recommendations on Organic & Biochemical Nomenclature, Symbols &
Terminology
etc.
2000.
ISBN
1-57259-153-6.
3. Carter, H. E.; West, H. D. dl-Serine Organic Syntheses, Collected Volume 3, p.774
Threonine
Threonine is an -amino acid with the chemical formula HO2CCH(NH2)CH(OH)CH3. Its three letter code
is thr, its one letter code is T, and its codons are ACU and ACA. This essential amino acid is classified as
polar. Together with serine and tyrosine, threonine is one of three proteinogenic amino acids bearing an
alcohol group.
The threonine residue is susceptible to numerous posttranslational modifications. The hydroxy side chain
can undergo O-linked glycosylation. Additionally, threonine residues undergo phosphorylation through the
action of a threonine kinase. In its phosphorylated form, it can be referred to as phosphothreonine.
1. Allo-threonine
With two chiral centers, threonine can exist in four possible stereoisomers, or two possible diastereomers
of L-threonine. However, the name L-threonine is used for one single enantiomer, (2S,3R)-2-amino-3hydroxybutanoic acid. The second diastereomer (2S,3S), which is rarely present in nature, is called Lallo-threonine.
2. Biosynthesis
As an essential amino acid, threonine is not synthesized in humans, hence we must ingest threonine or,
more commonly, threonine-containing proteins. In plants and microorganisms, threonine is synthesized
from aspartic acid via -aspartyl-semialdehyde and homoserine. Homoserine undergoes Ophosphorylation; this phosphate ester undergoes hydrolysis concomitant with relocation of the OH group.
[1] Enzymes involved in a typical biosynthesis of threonine include:
-aspartate
threonine synthase
semialdehyde
homoserine
homoserine
aspartokinase
dehydrogenase
dehydrogenase
kinase
Threonine biosynthesis
3. Metabolism
Threonine is metabolized in two ways:
It
is
converted
to
It is converted to alpha-ketobutyrate, and thereby enter the pathway leading to succinyl CoA.
pyruvate
4. Synthesis
Racemic threonine can be prepared from crotonic acid by alpha-functionalization using mercury(II)
acetate.[2]
5. Sources
Foods high in threonine include cottage cheese, poultry, fish, meat, lentils, and sesame seeds.
6. References
2000.
ISBN
1-57259-153-6.
2. Carter, H. E.; West, H. D. (1955). "dl-Threonine". Org. Synth.; Coll. Vol. 3: 813.
7. External links
Threonine
CID
CID 6288
biosynthesis
205
Tryptophan
Tryptophan is an amino acid essential in human nutrition. It is one of the 20 amino acids encoded by the
genetic code (as codon UGG). Only the L-stereoisomer appears in mammalian protein, however the Dstereoisomer is occasionally found in natural materials (for example, the marine venom peptide
contryphan[1]). A distinquishing structural characteristic of tryptophan is that it contains an indole
functional group.
Contents
1.
2.
2.1.
2.2.
3.
4.
5.
6. External links
Dietary
Use
Turkey
as
a
meat
Medicinal
dietary
and
Function
sources
supplement
drowsiness
uses
Fluorescence
References
1. Function
For many organisms including humans, tryptophan is an essential amino acid. This means that it cannot
be synthesized by the organism and therefore must be part of its diet. The principle function of amino
acids including tryptophan are as building blocks in protein biosynthesis. In addition, tryptophan functions
as a biochemical precursor for the following:
Serotonin (a neurotransmitter), via tryptophan hydroxylase. Serotinin, in turn, can be converted to
melatonin (a neurohormone), via 5-hydroxyindole-O-methyltransferase
Niacin (with kynurenine as an intermediate)
In organisms which synthesize tryptophan, high levels of this amino acid activate a repressor protein
which in turn binds to the trp operon. Binding of this repressor to its operon prevents transcription of
downstream DNA which codes for enzymes involved in the biosynthesis of tryptophan. Hence high levels
of tryptophan prevent additional tryptophan synthesis through a negative feedback loop. Conversely if the
cell's tryptophan level drops, transcription of the operon's genes resumes. This is one example of how
gene expression responds rapidly to changes in the cell's internal and external environment.
2. Dietary sources
Tryptophan, found as a component of dietary protein, is particularly plentiful[2] in chocolate, oats,
bananas, dried dates, milk, yogurt, cottage cheese, red meat, eggs, fish, poultry, sesame, chickpeas,
sunflower seeds, pumpkin seeds,spirulina and peanuts. It is found in turkey at a level typical of poultry in
general [1].
2.1. Use as a dietary supplement
For some time, tryptophan was available in health food stores as a dietary supplement. Since 2002, LTryptophan has been sold again in its original form. Many people found tryptophan to be a safe and
reasonably effective sleep aid, probably due to its ability to increase brain levels of serotonin (a calming
neurotransmitter when present in moderate levels) and/or melatonin (a sleep-inducing hormone secreted
by the pineal gland in response to darkness or low light levels).[3]
Clinical research tended to confirm tryptophan's effectiveness as a natural sleep aid and for a growing
variety of other conditions typically associated with low serotonin levels or activity in the brain.
(Particularly work by Dr. Richard Wurtman at MIT). In particular, tryptophan showed considerable promise
as an antidepressant alone, and as an "augmenter" of antidepressant drugs. Other promising indications
included relief of chronic pain and reduction of impulsive, violent, manic, addictive, anxiety-related,
obsessive,
and
compulsive
behaviours
and
disorders.
In 1989, a large outbreak of a new, disabling, and in some cases deadly autoimmune illness called
eosinophilia-myalgia syndrome (EMS) was traced to one source of L-tryptophan. The bacterial culture
used to synthesize tryptophan by a major Japanese manufacturer, Showa Denko KK, had been
genetically modified several times to increase tryptophan production during the 1980s.[4]
Along with the higher tryptophan concentrations in the modified culture media, the purification process
had also been streamlined to reduce costs, and a purification step that used charcoal absorption to
remove some impurities had been omitted.[5] The manufacturer maintained that this process modification
allowed another bacterial metabolite through the purification, resulting in the presence of an end-product
contaminant responsible for the toxic effects. As of 1996, Showa Denko had destroyed all modified
organisms without FDA receipt of culture samples.[6][7] The FDA was unable to publicly establish with
certainty what contaminant was the cause of the outbreak.
Most tryptophan was banned from sale in the US in 1991, and other countries followed suit. Tryptophan
from one manufacturer, of six, continued to be sold for manufacture of baby formulas. A Rutgers Law
Journal article observed, Political pressures have played a role in the FDAs decision to ban L-tryptophan
as well as its desire to increase its regulatory power over dietary supplements.[8]
At the time of the ban the FDA did not know, or did not indicate, that EMS was caused by a contaminated
batch,[9][10] and yet even when the contamination was discovered and the purification process fixed, the
FDA maintained that L-tryptophan was unsafe. In February 2001 the FDA loosened the restrictions on
marketing (though not on importation), but still expressed the following concern:
"Based on the scientific evidence that is available at the present time, we cannot determine with certainty
that the occurrence of EMS in susceptible persons consuming L-tryptophan supplements derives from the
content of L-tryptophan, an impurity contained in the L-tryptophan, or a combination of the two in
association with other, as yet unknown, external factors."[11]
2.2. Turkey meat and drowsiness
According to popular belief, eating tryptophan in turkey meat causes drowsiness. Turkey does contain
tryptophan, which does have a documented sleep-inducing effect as it is readily converted into serotonin
by the body. However, ingestion of turkey alone has not been proven to have this effect. An additional
hypothetical mechanism is as follows: A large quantity of any food,[original research?] such as a
Thanksgiving feast, introduces large quantities of both carbohydrates and branched-chain amino acids
releasing insulin. Insulin stimulates the uptake of large neutral branched-chain amino acids (and not
tryptophan) by muscle cells through the myocyte membranes. The result is an increase in the ratio of
tryptophan to large neutral amino acids in the blood. This reduces competition with other amino acids for
the Large Neutral Amino Acid Transporter protein for uptake of tryptophan across the blood-brain barrier
into the central nervous system. Once inside the central nervous system, tryptophan is converted into
serotonin by the raphe nuclei, and serotonin is further metabolised into melatonin by the pineal gland.
Alcoholic beverage consumption at holiday feasts is likely to compound the effect.[original research?]
3. Medicinal uses
5-Hydroxytryptophan (5-HTP), a metabolite of tryptophan, has been suggested as a treatment for
epilepsy[12] and depression though clinical trials are inconclusive and lacking.[13]
5-HTP readily crosses the blood brain barrier and in addition is rapidly decarboxylated to serotonin (5hydroxytryptamine or 5-HT)[14] and therefore may useful for the treatment of depression. However
serotonin has a relatively short half life since it is rapidly metabolized by monoamine oxidase therefore is
likely to have limited efficacy. It is marketed in Europe for depression and other indications under brand
names like Cincofarm and Tript-OH.
In the United States, 5-HTP does not require a prescription as it is covered under the Dietary Supplement
Act. However, since the quality of dietary supplements is not regulated by the FDA, the quality of dietary
and nutritional supplements tends to vary and there is no guarantee that the label accurately depicts what
the bottle contains.
In recent years, compounding pharmacies and some mail-order supplement retailers have begun selling
tryptophan to the general public. Tryptophan has also remained on the market as a prescription drug
(Tryptan) which some psychiatrists continue to prescribe, particularly as an augmenting agent for people
who are unresponsive to antidepressant drugs. Also, most health-food stores sell 5-HTP to get around the
resulting artificially high cost of the amino acid itself. But several high quality sources of L-Tryptophan do
exist, and are sold in many of the largest health food stores nationwide. Indeed, tryptophan has continued
to be used in clinical and experimental studies employing human patients and subjects. Several of these
studies suggest tryptophan can effectively treat the fall/winter depression variant of seasonal affective
disorder.[15]
4. Fluorescence
The fluorescence of a folded protein is a mixture of the fluorescence from individual aromatic residues.
Most of the intrinsic fluorescence emissions of a folded protein are due to excitation of tryptophan
residues, with some emissions due to tyrosine and phenylalanine. Typically, tryptophan has a wavelength
of maximum absorption of 280 nm and a wavelength of maximum fluorescence emission of 350 nm.
However these fluorescence parameters are strongly dependent on the environment that the tryptophan
residue is in, for example the degree of solvent exposure.[16] Hence protein fluorescence may be used
as a diagnostic of the conformational state a protein.[17]
Furthermore, tryptophan fluorescence is strongly influenced by the proximity of other residues (i.e.,
nearby protonated acidic groups such as Asp or Glu can cause quenching of Trp fluorescence). In
addition, tryptophan is a relatively rare amino acid therefore many proteins contain only one or a few
tryptophan residues. Therefore, tryptophan fluorescence is a very sensitive measurement of the
conformational state of individual tryptophan residues.
5. References
1. Pallaghy PK, Melnikova AP, Jimenez EC, Olivera BM, Norton RS (1999). "Solution structure of
contryphan-R, a naturally occurring disulfide-bridged octapeptide containing D-tryptophan: comparison
with
protein
loops".
Biochemistry
38
(35):
11553-9.
2. Tryptophan
background
3. Wurtman RJ, Shoemaker WJ, Larin F (1968). "Mechanism of the daily rhythm in hepatic tyrosine
transaminase activity: role of dietary tryptophan". Proc Natl Acad Sci U S A 59 (3): 800-7.
4. Smith, Jeffrey M (September 2003). "Chapter 4: Deadly Epidemic", Seeds of Deception: Exposing
Industry and Government Lies About the Safety of the Genetically Engineered Foods You're Eating.
Fairfield,
Iowa
52556:
Yes!
Books,
pages
107-127.
ISBN
978-0972966580.
5. Mayeno AN, Gleich GJ (1994). "Eosinophilia-myalgia syndrome and tryptophan production: a
cautionary
tale".
Trends
Biotechnol
12
(9):
346-52.
6.
James
Maryanski.
FDA.
July
5,
1996.
7. Page S. Center for Food Safely and Applied Nutrition, FDA, Congressional Hearing, Subcommittee,
July
18,
1991.
8. Beisler JH (2000). "Dietary Supplements and Their Discontents: FDA Regulation and the Dietary
Supplement Health and Education Act of 1994 (L-tryptophan Section)". Rutgers Law Journal.
9. FDA
Tryptophan
Recall
10. Raphals P (2000). "Does medical mystery threaten biotech?". Science 250: 4981.
DOI:10.1126/science.2237411.
11. FDA
Information
Paper
on
L-tryptophan
and
5-hydroxy-L-tryptophan
12. Kostowski W, Bidzinski A, Hauptmann M, Malinowski JE, Jerlicz M, Dymecki J (1978). "Brain
serotonin and epileptic seizures in mice: a pharmacological and biochemical study". Pol J Pharmacol
Pharm
30
(1):
41-7.
13. Turner EH, Loftis JM, Blackwell AD (2006). "Serotonin a la carte: supplementation with the serotonin
precursor
5-hydroxytryptophan".
Pharmacol
Ther
109
(3):
325-38.
14. Hardebo JE, Owman C (1980). "Barrier mechanisms for neurotransmitter monoamines and their
precursors
at
the
blood-brain
interface".
Ann
NeurolAnn
Neurol
8
(1):
1-31.
15. Jepson TL, Ernst ME, Kelly MW (1999). "Current perspectives on the management of seasonal
affective
disorder".
J
Am
Pharm
Assoc
(Wash)
39
(6):
822-9.
16. Intrinsic
Fluorescence
of
Proteins
and
Peptides
17. Vivian JT, Callis PR (2006). "Mechanisms of tryptophan fluorescence shifts in proteins". Biophys J 80
(5): 2093-109.
6. External links
Tryptophan
catabolism
(early
stages)
Tryptophan
catabolism
(later
stages)
FDA
Information
Paper
on
L-tryptophan
and
5-hydroxy-L-tryptophan
The
FDA
Ban
of
L-Tryptophan:
Politics,
Profits
and
Prozac
Effects of Tryptophan Depletion on the Performance of an Iterated Prisoner's Dilemma Game in Healthy
Adults - Nature Neuropsychopharmacology
Tyrosine
Tyrosine, 4-hydroxyphenylalanine, or 2-amino-3(4-hydroxyphenyl)-propanoic acid, is one of the 20 amino
acids that are used by cells to synthesize proteins. It has a phenol side chain with a hydroxyl group. Upon
the location of the hydroxyl group, there are three structural isomers of Tyr, namely para-Tyr (p-Tyr),
meta-Tyr (m-Tyr) and ortho-Tyr (o-Tyr). Enzymatically, only the first isomer (p-Tyr) is produced from L-Phe
by the Phe-hydroxylase enzyme. The other two isoforms, m-Tyr and o-Tyr can be produced as a
consequence of free radical attack on Phe in states with increased oxidative stress.
Tyrosine is converted to levodopa by tyrosine hydroxylase, an enzyme.

Some of the tyrosine residues can be tagged with a phosphate group (phosphorylated) by protein
kinases. (In its phosphorylated state, it is referred to as phosphotyrosine.). Tyrosine phosphorylation is
considered as one of the key steps in signal transduction and regulation of enzymatic activity.
Phosphotyrosine can be detected through specific antibodies. Tyrosine residues may also be modified by
the addition of a sulfate group, a process known as tyrosine sulfation. Tyrosine sulfation is catalyzed by
tyrosylprotein sulfotransferase (TPST). Like the phosphotyrosine antibodies mentioned above, antibodies
have recently been described that specifically detect sulfotyrosine. Tyrosine is also precursor to the
thyroid hormones thyroxine and triiodothyronine, the pigment melanin, and the biologically-active
catecholamines dopamine, norepinephrine and epinephrine.
In Papaver somniferum, the opium poppy, it is used to produce morphine.

1. Biosynthesis
Tyrosine cannot be completely synthesized by animals, although it can be made by hydroxylation of
phenylalanine if the latter is in abundant supply. It is produced by plants and most microorganisms from
prephenate, an intermediate on the shikimate pathway.
Prephenate is oxidatively decarboxylated with retention of the hydroxyl group to give phydroxyphenylpyruvate. This is transaminated using glutamate as the nitrogen source to give tyrosine and
-ketoglutarate.
2. Tyrosine hydroxylase
Tyrosine hydroxylase (TH) is the rate-limiting enzyme involved in the synthesis of the catecholamines
such as dopamine, norepinephrine and epinephrine.
3. Medical use
L-Tyrosine is sometimes recommended by practitioners as helpful for weight loss, clinical depression,
Parkinson's Disease, and phenylketonuria; however, one study found that it had no impact on endurance
exercise performance. [1]
4. References
1. Parcell A.C., et al. Effects of L-tyrosine and carbohydrate ingestion on performance. Journal of Applied
Physiology 2002 Nov; 93(5): 1590-97. Abstract
5. Notes
AJ
Hoffhines
et
al.
Journal
of
Biological
Chemistry
GA
Molnar
et
al.
Kidney
International
GA Molnar et al. Free Radical Research 39(12):1359-1366, 2005
281:37877-37887,
68:2281-2287,
2006
2005
6. External links
Phenylalanine
Phosphotyrosine Antibody
Valine
and
tyrosine
biosynthesis
Valine is an -amino acid with the chemical formula HO2CCH(NH2)CH(CH3)2. Its three letter code is Val,
its one letter code is V, and its codons are GUU, GUC, GUA, and GUG. This essential amino acid is
classified as nonpolar. Along with leucine and isoleucine, valine is a branched-chain amino acid. It is
named after the plant valerian. In sickle-cell disease, valine substitutes for the hydrophilic amino acid
glutamic acid in hemoglobin. Because valine is hydrophobic, the hemoglobin does not fold correctly.
1. Biosynthesis
As an essential amino acid, valine is not synthesized in animals, hence it must be ingested, usually as a
component of proteins. It is synthesized in plants via several steps starting from pyruvic acid. The initial
part of the pathway also leads to leucine. The intermediate -ketovalerate undergoes reductive amination
with glutamate. Enzymes involved in this biosynthesis include:[1]
acetohydroxy
valine aminotransferase
acetolactate
acid
dihydroxyacid
synthase
isomeroreductase
dehydratase

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ALANINE

The biosynthesis of asparagine from oxaloacetate

1. Role in biosynthesis of amino acids

-ketoglutarate + NADPH + NH4+

Glu + NADP+ + H2O

-ketoglutarate + -amino acid

Glu + -oxo acid

1-pyrroline-5-carboxylate + NAD+ + H2O

1. Nelson DL and Cox MM. Lehninger Principles of Biochemistry, 4th edition.

Conversion of histidine to histamine by histidine decarboxylase

CID 791 CID 94206 CID 6306

207-139-8 206-269-2 200-798-2

CAS number: 443-79-8 319-78-8

2. Other biochemical pathways

Methionine is converted to S-adenosylmethionine (SAM) by (1) methionine adenosyltransferase. SAM

2. Barger, G.; Weichselbaum, T. E. dl-Methionine Organic Syntheses, Collected Volume 2, p.384

Tyrosine is converted to levodopa by tyrosine hydroxylase, an enzyme.

In Papaver somniferum, the opium poppy, it is used to produce morphine.

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