Unit I

NITROGEN METABOLISM.
Index with hyperlinks.
1.1. Nitrogen metabolism.

1.2 Degradation of aminoacid. Degradation of amino acids

Amino acid biosynthesis

1.3 Nitrogen excretion and urea cycle.

Video of the nitrogen cycle.
1.4 Nitrogen cycle.

1.5 Biosynthesis of amino acids.

1.1 Nitrogen metabolism.
Biomoléculas
También se les suele llamar macromoléculas o moléculas de la vida.
Se basan en la combinación de átomos de carbono, hidrógeno ,
oxígeno, nitrógeno y otros elementos como el azufre y el fósforo
Hay cuatro tipos:

• Carbohidratos
• Lípidos
• Proteínas
• Ácidos nucleicos
Molécula de un lípido
 78% de nitrógeno, 21%
de oxígeno y el 1%
restante se compone de
gases como el dióxido de
carbono, argón, neón,
helio, hidrógeno, otros
gases y vapor de agua.

Although reduced nitrogen, either as ammonia or as amino acids, are the forms used for most
living organisms, some soil bacteria get their energy by oxidizing ammonia with nitrite formation,
and from it, nitrate. The nitrification is performed in two stages. In the first, ammonia is oxidized
to nitrite almost exclusively by the aerobic chemolithrophic organism Nitrosomes.
For this effect, ammonia plays the role of energy-contributing fuel, since it constitutes the main
electron donor in the respiration of the Nitrosomes. Electrons flow from the primary system of
amino-dehydrogenase to oxygen, passing along a respiratory chain, containing cytochrome;
Coupled to this electronic transport of oxidative phosphorylation. Then the nitrite is oxidized to
nitrate, similarly by Nitrobacter, which gets its energy almost exclusively from the oxidation of
the nitrite. Both nitrosomes and nitrobacter get the carbon they need for their growth from CO2.
Protein of degradation
Cells continuously synthesize proteins from amino acids and degrade them in order to:
• Store nutrients in the form of protein and degrade them in times of metabolic need.
• Remove abnormal proteins whose accumulation would be harmful to the cell.
• They allow the cellular regulation by the elimination of enzymes and regulatory proteins
that are superfluous. – Environmental toxins, translation errors and genetic mutations can
damage proteins.
• Misfolded proteins are highly deleterious to the cell because they can form non-
physiological interactions with other proteins.
• The rate of degradation of proteins will depend on the feed and hormonal activity.
Cellular functions of protein degradation
4. The recycling of amino acids
Generate free amino acids from short peptides that are generated by the proteasome and other
intracellular proteases.
2. Monomeric subunits of proteins

All proteins are composed of some or all of the 20

"standard" amino acids
 Serylglycyltyrosylalanylleucine.

Ser-Gly-Tyr-Ala-Leu

SGTAL

N-terminus C-terminus
 Hierarchy of protein structures:

 Multisubunit proteins.
Subunits: noncovalent association,
 and  subunits of hemoglobin
Chains: covalently bonded (via disulfide bonds),
A and B chains of insulin
Rough estimation of MW of proteins:
Number of a. a. residues  110
[1] Amino Acids

(1) Description
 The “standard” amino acids are -amino acids.
‒ primary amino group (NH2)
‒ carboxylic acid group (COOH)

Proline is an exception
with a secondary amino group,
but, it is still referred to
as an -amino acid.
 Amino acids also exist in a zwitterionic form at pH 7.
The amino group is protonated (pKa ~9.4).
The carboylic acid group is deprotonated
(carboxylate; pKa ~2.2).

 Amino acid structures differ at the side chain (R-groups).

 Abbreviations: three or one letter codes
 Amino acids (except glycine)
have chiral centers:
- Rotate the plane of
plane-polarized light
and are optically active.
Amino acid carbons are named in sequence
using the Greek alphabet (, , , , ) starting at
the carbon COO
between the carboxyl and amino groups. H3N CH 
CH2 
CH2 
CH2 
CH2 
NH 3
 Configuration of biological chiral compounds is defined in relation to glyceraldehyde (L- & D-)
D - dextrorotatory (rotating light to the right)
L - levorotatory (rotating light to the left)

BUT L or D designation for an amino acid does NOT reflect its ability to rotate plane polarized light in a
particular direction!
 The amino acids in proteins are L isomers.

COO COO H
3 2
H3N C H H3N C H H3C C COO

CH3 CH3 S 1 NH 3

L-Alanine (S)-Alanine
(2) Amino Acids: Structural Classification (Table 3-1, p. 78)
 Cystine residues provide structural stability of proteins
through intramolecular or intermolecular disulfide bonds.

Oxidation

Reduction
Disulfide bonds and
permanent waving.

Box 4-2, p.127

1.2. Aminoacid degradation
 OVERVIEW OF AMINO ACID METABOLISM

ENVIRONMENT ORGANISM

Bio-
Ingested synthesis Protein
protein
2 3
1
a
AMINO
ACIDS
b
c c
Degradation Purines
Pyrimidines
(required) Porphyrins
Carbon
Nitrogen
skeletons
(ketogenic) (glucogenic)
Urea Used for
energy pyruvate
acetoacetate α-ketoglutarate
acetyl CoA succinyl-CoA
fumarate
oxaloacetate
In general, the amino group must be removed from the amino acid structure and transported
safely until its removal from the body.
The resulting carbon skeleton is metabolized.
The presence of α-amino groups effectively protects amino acids against oxidative degradation,
then elimination of the amino group is essential for the generation of energy from any amino
acid and is a mandatory step in the catabolism of all amino acids.
• Turnover of normal, unmodified proteins
– Enzymatic hydrolysis, not chemical reactions
– Use energy
– Use the AAs for the synthesis of new proteins
– Regulated during development, the cell cycle and in response to changes in the
environment
The carbon skeletons of amino acids are broken down into metabolites that can either be
oxidized into CO2 and H2O to generate ATP, or can be used for gluconeogenesis. The catabolism
of amino acids accounts for 10 to 15% of the human body’s energy production. Each of the 20
amino acids has a separate catabolic pathway, yet all 20 pathways converge into 5 intermediates,
all of which can enter the citric acid cycle. From the citric acid cycle the carbon skeletons can be
completely oxidized into CO2 or diverted into gluconeogensis or ketogenesis.
Glucogenic amino acids are broken down into one of the following metabolites: pyruvate, α-
ketoglutarate, succinyl CoA, fumarate or oxaloacetate. Ketogenic amino acids are broken down
into acetoacetate or acetyl-CoA. Larger amino acids, tryptophan, phenylalanine, tyrosine,
isoleucine and threonine are both glucogenic and ketogenic. Only 2 amino acids are purely
ketogenic they are lysine and leucine. If 2 of the amino acids are purely ketogenic and 5 amino
acids are both ketogenic and glucogenic, than that leaves 13 amino acids that are purely
glucogenic: Arg, Glu, Gln, His, Pro, Val, Met, Asp, Asn,Ala, Ser, Cys, and Gly.
I. Amino Acids that are Catabolized into Pyruvate.
Pyruvate is the entry point for amino acids that contain 3 carbons, alanine, serine and cysteine.
Alanine transaminase reversibly transfers the amino group from alanine to α-ketoglutarate to
form pyruvate and glutamate. Note that enzyme requires a pyridoxal phosphate cofactor. The α-
ketoglutarate is regenerated by glutamate dehydrogenase.
Serine dehyratase is another enzyme that requires a pyridoxal phosphate cofactor. This enzyme
catalyzes the β-elimination of the hydroxyl group of serine to form an amino acrylate
intermediate which tautomerizes into the imine which is then hydrolyzed to produce ammonia
and pyruvate.
Glycine is converted into pyruvate via conversion of glycine to serine by serine hydroxymethyl
transferase which is an incredibly interesting enzyme. It contains a pyridoxal phosphate cofactor
and a N5 ,N10-methylene-tetrahydrofolate which is a cofactor we have not encountered yet. The
N5 ,N10- methylene-tetrahydrofolate is produced by the glycine cleavage system which transfers
a methylene group from glycine to THF. The THF cofactor is a one carbon acceptor and donor. We
will discuss this cofactor further when we get to amino acid biosynthesis.
They are several pathways by which cysteine is converted into pyruvate. The three alkyl carbons
of trypophan are converted into alanine which is then converted by alanine transaminase into
pyruvate. Threonine is both glucogenic and ketogenic. There are a couple of routes for the
degradation of threonine. The major route is shown below. Threonine is converted into acetyl
CoA and glycine. Glycine is then converted into serine by serine hydroxymethyl transferase, and
serine is then converted into pyruvate by serine dehydratase.
II. Amino Acids Degradated to Oxaloacetate.
Aspartate and asparagines are both degraded into oxaloacetate. Asparagine is hydrolyzed into
aspartate and ammonia by asparaginase. Aspartate is converted into oxaloacetate by aspartate
amino transferase which is a PLP enzyme that transfers an amino group from aspartate to
α−ketoglutarate to form glutamate and oxaloacetate.
III. Amino Acids Degraded to α-Ketoglutarate.
Glutamine, proline, arginine and histidine are converted into glutamate which is then
deaminated by a transaminase to form α-ketoglutarate. Glutamine is converted into glutamate
by glutaminase. Proline is oxidized by proline oxidase to form pyrroline 5-carboxylate which
spontaneously hydrolyzes to from glutamate γ-semialdehyde. From the urea cycle we know that
arginase converts arginine into ornithine and urea. Ornithine δ-aminotransferase transfers the δ-
amino group of ornithine to α-ketoglutarate to form glutamate γ-semialdehyde and glutamate.
Glutamate γ-semialdehyde is oxidized to form glutamate by glutamate -5-semialdehyde
dehydrogenase.
Histidine is deaminated by histidine ammonia lyase which forms urocanate. Urocanate hydratase
adds water to form 4-Imidazolone-5-propionate which is hydrolyzed by imidazalone propionase
to form Mformiminoglutamate. Glutamate formiminotransferase transfers the formimino group
to tetrahydrofolate to generate glutamate and N5 -formimino-THF.
IV. Amino Acids that are Broken Down in Succinyl-CoA.
Methionine, valanine and isoleucine are broken down into propoinyl CoA. By studying β-
oxidation of odd chain fatty acids we know that propionyl CoA is converted into D-methylmalonyl
CoA by propionyl CoA carboxylase. D-methylmalonyl CoA is racemized into L-methylmalonyl CoA
by methylmalonyl CoA racemase. Methylmalonyl mutase produces succinyl CoA.
The degradation of methionine requires 9 steps. One of which involves the synthesis of
Sadenoylmethionine (SAM). The methyl group of SAM is highly reactive making it an important
methylating reagent. SAM is a common methyl-group donor in the cell. The degradation of
methionine is shown on the next page. The first step is catalyzed by methionine adenosyl
transferase which tranfers the adenosyl group of ATP to the sulfer of methionine to form SAM.
Sam methylase transfers the activated methyl group to an acceptor to form S-
adenosylhomocysteine which is hydrolyzed by adenosylhomocysteinase to form homocysteine.
Cystathionine β-synthase is a PLP dependent enzyme that catalyzes the condensation of a serine
residue with homocysteine to form cystathionine.
Branched Chain Amino Acids The degradation of branched chain amino acids uses some of the
enzymes we have already encountered in the citric acid cycle or β-oxidation.
V. Amino Acids that are degraded into Acetyl CoA and Acetoacetate.
There are only two amino acids that are purely ketogenic, lysine and leucine. Leucine catabolism
is similar to the branched amino acids valine and isoleucine.
First leucine is transaminatedby branched amino acid aminotransferase to form α-
ketoisocaproate which is then oxidatively decarboxylated to form isovaleryl CoA by the branched
chain α-ketoacid dehydrogenase complex we just discussed. In the next step isovaleryl CoA is
dehydrogenated to form β- methylcrotonyl CoA. The enzyme that catalyzes this dehydrogenation
is isovaleryl CoA dehydrogenase. β-methylcrotonyl CoA is then carboxylated by a biotin
containing enzyme called methylcrotonyl CoA carboxylase to form β-methylglutaconyl CoA
β-methylglutaconyl CoA is then hydrated by β-methylglutaconyl CoA. hydratase to form β-
hydroxy-β- methylglutaryl CoA which is then cleaved into acetyl CoA and acetoacetate. The
enzyme that catalyzes the last step is HMG-CoA lyase, a familiar enzyme from ketogenesis.
VI. Catabolism of Aromatic Amino acids.
The degradation of aromatic amino acids requires molecular oxygen to break down the aromatic
rings.
• The degradation of phenylalanine begins with a monooxygenase, phenylalanine hydroxylase
which adds a hydroxyl group to phenylalanine to from tyrosine.
• Tyrosine aminotransferase deaminates tyrosine to form phydroxyphenylpyruvate.
• p-hydroxyphenylpyruvate dioxygenase catalyzes the formation of homogentisate.
• Homogentisate 1,2-dioxygenase catalyzes the formation of maleylacetoacetate.
• Maleylacetoacetate isomerase produces fumarylacetoacetate.
• Fumarylacetoacetase produces fumarate and acetoacetate.
Tryptophan catabolism is shown below:
 Transamination

• Channeling of amino groups to glutamate

• Transaminases or amino transferasas.
• Transfer of the amino group to α-ketoglutarate.
• The products are an α-keto acid and glutamate.
• Α-Ketoglutarate accepts the amino groups of other amino acids by becoming glutamate.
• The produced glutamate can be oxidatively deaminated or used as a donor of amino groups in
amino acid synthesis.
• This transfer of amino groups from one carbon skeleton to another is catalyzed by the
aminotraspherase or transaminase enzymes present in the mitochondria of all cells especially
in the liver, kidney, intestine and muscle.
 Oxidative deamination

By the action of glutamate dehydrogenase (GDH) causes the release of the amino group in the
form of free ammonia and regenerates α-ketoglutarate. These reactions occur mainly in the liver
and kidney and free ammonia goes to the liver.
1.3 Nitrogen excretion and urea cycle.
Living organisms excrete excess nitrogen arising from the metabolic degradation of amino acids
by some of the following three ways:
1. Aquatic animals simply excrete ammonia by the Ammonoteolitic method.
2. Most terrestrial vertebrates do this by the ureoteoltic method urea is synthesized in the liver
by the enzymes of the urea cycle, then secreted into the bloodstream, and the kidneys trap it for
urine excretion.
3. Birds and reptiles secrete uric acid the process is called uricothelitic.
 Cycle of urea

Global reaction of the urea cycle.

The two nitrogen atoms of urea are supplied by ammonia and aspartate, while their carbon atom
comes from HCO3.
Also called ornithine cycle, Krebs urea cycle, and Krebs-Henseleit cycle, is the central route of
nitrogen metabolism and this comes from several sources was discovered by Hans Krebs and kart
Henseleit, in the cycle is eliminated approximately 90% to 95% of the excess nitrogen.
• In the urea cycle, five enzymatic reactions are involved, two of which are mitochondrial and
three cytosolic.
Step 1: formation of Carbamoyl phosphate from ammonia, bicarbonate and ATP
• Enzyme Carbamoyl phosphate synthetase I.
• In liver cell mitochondrias.
• Ammonia released from the oxidative deamination of glutamate, by mitochondrial glutamate
dehydrogenase, is incorporated in carbamoyl phosphate by using ATP and bicarbonate.
• Utilizes 2 ATP .
• Requires Mg +
• Carbamoyl phosphate synthetase I requires N-acetylglutamate as a positive allosteric activator.
The reaction is irreversible.
• Carbamoyl Phosphate Synthase (Type I) catalyzes a 3-step reaction, with carbonyl
phosphate and carbamate intermediates. Carbamoyl phosphate O HO C O OPO 3 2
− HCO 3 − NH 3 ADP ATP Pi carbonyl phosphate
• Carbamoyl phosphate synthetase (type)II participates in the biosynthesis of
pyrimidines, It does not require Nacetylglutamate, and occurs in the cytosol.
Step 2: Formation of citrulline from ornithine and carbamoyl phosphate
Enzyme Ornithine transcarbamoylase
• In liver mitochondria
• Citrulline is formed from transfer of the carbamoyl group to the γ- amino group of ornithine.
• The release of the high -energy phosphate of carbamoyl phosphate as inorganic phosphate
drives the reaction in the forward direction.
• Citrulline passes from mitochondrial membrane to cytosol • Ornithine is regenerated with each
turn of the urea cycle.
Step 3: Formation of arginosuccinate from citrulline and aspartate
• This is the second nitrogen-acquiring reaction.
• Condensation of citrulline with aspartate to form arginosuccinate.
• The α-amino group of aspartate provides the second nitrogen that is ultimately incorporated
into urea.
• Enzyme Argininosuccinate synthetase.
• Requires ATP and Mg +
Step 4: Formation of arginine and fumarate from arginosuccinate
• Enzyme Argininosuccinase
• Liver and kidney of mammals
• Cleaves arginosuccinate to form arginine and fumarate.
• The arginine formed by this reaction serves as the immediate precursor of urea.
• Fumarate produced in the urea cycle is hydrated to malate, providing a link with several
metabolic pathways. For example, the malate can be transported into the mitochondria via the
malate shuttle and reenter the tricarboxylic acid cycle. Alternatively, cytosolic malate can be
oxidized to oxaloacetate, which can be converted to aspartate or glucose. ((thus aspartate could
be regenerated)
Step 5: Hydrolysis of arginine to form ornithine and urea
• Enzyme Arginase
• The arginine is hydrolyzed to produce the urea and to reform the ornithine. • In liver cells
cytosol.
• The ornithine reenters the mitochondrial matrix.
• Urea excreted (N rich, excelent solubility, harmless )
• Thus, whereas other tissues, such as the kidney, can synthesize arginine by these reactions,
only the liver can cleave arginine and, thereby, synthesize urea.
Fate of urea
• Urea diffuses from the liver, and is transported in the blood to the kidneys, where it is filtered
and excreted in the urine.
• A portion of the urea diffuses from the blood into the intestine, and is cleaved to CO2 and NH3
by bacterial urease.
• This ammonia is partly lost in the feces, and is partly reabsorbed into the blood.
• In patients with kidney failure, plasma urea levels are elevated, promoting a greater transfer of
urea from blood into the gut.
• The intestinal action of urease on this urea becomes a clinically important source of ammonia,
contributing to the hyperammonemia often seen in these patients.
Regulation of urea cycle
• The Activity of the Urea Cycle Is Regulated at Two Levels :the level of urea cycle enzyme
synthesis and by allosteric regulation of the enzyme carbamoyl phosphate synthetase I.
• The flux of nitrogen through the urea cycle in an individual animal varies with diet. When the
dietary intake is primarily protein, the carbon skeletons of amino acids are used for fuel,
producing much urea from the excess amino groups.
• During prolonged starvation, when breakdown of muscle protein begins to supply much of the
organism’s metabolic energy, urea production also increases substantially.
Regulation of urea cycle cont.:
•The carbamoyl phosphate synthetase I, is allosterically activated by N-acetylglutamate, which is
synthesized from acetyl- CoA and glutamate by Nacetylglutamate synthase.
•The steady-state levels of Nacetylglutamate are determined by the concentrations of glutamate
and acetyl-CoA (the substrates for N-acetylglutamate synthase) and arginine(an activator of N-
acetylglutamate synthase, and thus an activator of the urea cycle).
Aspartate –Arginosuccinate Shunt Links Urea Cycle and Citric Acid Cycle.
• Each cycle can operate independently and communication between them depends on the
transport of key intermediates between the mitochondrion and cytosol.
• Several enzymes of the citric acid cycle, including fumarase (fumarate hydratase) and malate
dehydrogenase, are also present as isozymes in the cytosol.
• The fumarate generated in cytosolic arginine synthesis can therefore be converted to malate in
the cytosol, and these intermediates can be further metabolized in the cytosol or transported
into mitochondria for use in the citric acid cycle.
• Aspartate formed in mitochondria by transamination between oxaloacetate and glutamate can
be transported to the cytosol, where it serves as nitrogen donor in the urea cycle reaction
catalyzed by argininosuccinate synthetase.
1.4 Cycle of nitrogen.
1.5 Biosynthesis of amino acids.
Many amino acids are synthesized through pathways that only exist in plants and
microorganisms, mammals extract essential amino acids through diet and nonessential amino
acids are synthesized by common intermediaries.
Biosynthesis of non-essential amino acids Non-essential or dispensable amino acids are defined
as those that can be synthesized by man and the rat albino, organisms that exhibit identical
amino acid needs.
These amino acids are characterized because their biosynthetic pathways are relatively short.
(Glutamic acid, glutamine and proline). All the non-essential amino acids are synthesized
through simple pathways that start from one of the four metabolic intermediates: pyruvate,
oxalacetate, α-ketoglutarate, 3-phosphoglycerate.
Biosynthesis of Essential Amino Acids The routes of synthesis of essential amino acids in rat and
human nutrition have been derived mainly from biochemical and genetic studies carried out with
bacteria. In general, the pathways of this group of amino acids are similar, if not identical, in most
bacteria and higher plants. However, there are sometimes species differences in certain
individual links. Biosynthetic pathways leading to essential amino acids are more complex and
longer (5 to 15 links) than those of non-essential amino acids, most of which comprise less than
five stages (threonine and methionine).
BIOSYNTHESIS OF AMINO ACIDS
BIOSYNTHESIS OF AMINO ACIDS

An overview of amino acid biosynthesis Precursors from glycolysis, the citric acid cycle and the
pentose phosphate pathway have been shown enclosed in single-line, double-line and dashed-
line rectangles, respectively.
Syntheses of Amino Acids of a-ketoglutarate Precursor Family
The biosynthesis of glutamate and glutamine has already been discussed earlier in this
chapter. The synthesis of proline, a cyclized derivative of glutamate.
In the first reaction, the carboxyl group of glutamate is phosphorylated using ATP to form an acyl.
Biosynthesis of proline from glutamate
Note that all 5 carbon atoms of proline arise from glutamate. The nonenzymatic
cyclization of glutamate semialdehyde is so rapid that the semialdehyde cannot give rise
to ornithine via transamination.
Biosynthesis of arginine from glutamate
Note that, in contrast to proline pathway, cyclization is averted in ornithine/arginine pathway by
acetylating
the amino group of glutamate in the first step and removing the acetyl group after the
transamination.
Arginine is synthesized from ornithine via the urea cycle
Syntheses of Amino Acids of 3-phosphoglycerate Precursor Family

serine from 3-phosphoglycerate and the subsequent conversion of serine into glycine
Biosynthesis of cysteine from homocysteine and serine
Biosynthesis of lysine, methionine and threonine
Note that L-L-, -diaminopimelate, the product of Step 7 is symmetric. The carbons
derived from pyruvate (and amino group derived from glutammate) cannot be traced
beyond this point because subsequent reactions may place them at either end of the
lysine molecule. The enzymes involved in the numbered reactions are :
1 aspartokinase, 2 asparatate -semialdehyde dehydrogenase, 3 dihydropicolinate
synthase, 4 -piperidine-2, 6-dicarboxylate dehydrogenase, 5 Nsuccinyl-2-amino-6
ketopimelate synthase, 6 succinyl diaminopimelate aminotransferase (a PLP enzyme), 7
succinyl diaminopimelate desuccinylase
8 diaminopimelate epimerase, 9 diaminopimelate decarboxylase, 10 homoserine
dehydrogenase, 11 homoserine acyltransferase, 12 cystathionine-synthase, 13
cystathionine--lyase, 14 methionine synthase, 15 homoserine kinase and 16 theronine
synthase ( a PLP enzyme).
Biosynthesis of isoleucine and valine
Note that pyruvate is the metabolic precursor for both isoleucine and valine pathways. The
pathway enzymes for the numbered reactions are :
1 and 2 acetoacetate synthase ( a TPP enzyme), 3 acetohydroxy acid isomeroreductase, 4
dihydroxy acid dehydratase and 5 valine aminotransferase ( a PLP enzyme).
Biosynthesis of leucine
Note that α-ketoisovalerate, an intermediate in valine pathway, is the starting point for
leucine synthesis. The enzymes involved in the numbered reactions are : 1 α -
isopropylmalate synthase, 2 isopropylmalate -isopropylmalate isomerase, 3
dehydrogenase, and 4 leucine aminotransferase (a PLP enzyme).
Syntheses of Amino Acids of Oxaloacetate and Pyruvate Precursor Families.

Alanine and aspartate are synthesized from pyruvate and oxaloacetate respectively, by
transamination from glutamate. Asparagine is then synthesized by amidation of aspartate; the
NH4 being donated by glutamine. These are all nonessential amino acids and their simple
biosynthesis occurs in all organisms. The biosynthetic pathways for the 6 of the essential amino
acids, viz., methionine, threonine, lysine, isoleucine, valine and leucine, are complex and
interlinked. In some cases, there are marked differences in the pathways found in bacteria, fungi
and higher plants.
Synthesis of Amino Acids of Phosphoenolpyruvate–erythrose-4-phosphate Precursor Family.

Synthesis of chorismate, a key intermediate in the synthesis of the aromatic amino acids.
Note that all carbons are derived from either erythrose-4-phosphate or phosphoenolpyruvate.
The pathway enzymes for the numbered reactions are:
: 1 2-keto-3-deoxy-D-arabinoheptulosonate-7-phosphate synthase, 2 dehydroquinate synthase, 3
3-dehydroquinate dehydrogenase, 4 shikimate dehydrogenase, 5 shikimate kinase, 6 3-
enolpyruvylshikimate-5-phosphate synthase, and 7 chorismate synthase. Note that Step 2
requires NAD+ as a cofactor, and NAD+ is released unchanged. It may be
transiently reduced to NADH during the reaction to produce an oxidized reaction intermediate.
Biosynthesis of tryptophan from chorismate
The pathway enzymes for the numbered reactions are : 1 anthranilate synthase, 2 anthranilate
phosphoribosyl transferase, 3 N-(5’-phosphoribosyl)- anthranilate isomerase, 4 indole-3-glycerol
phosphate synthase, and 5 tryptophan synthase.
Biosynthesis of tyrosine and phenylalanine from chorismate
The enzymes inovled in the numbered reactions are : 1 chorismate mutase, 2 prephenate
dehydrogenase, and 3 prephenate dehydratase.