AMINO ACIDS Based on nutritional requirements

Organic molecule that linked together with each other by Based on metabolic fate
peptide bond to form a protein
Chemical properties= determine biologic activity of Based on structure
protein A. Aliphatic Amino acids
Building blocks of proteins - Both Non Polar and Hydrophobic (water-fearing)
There are 20 amino acids - Hydrophobicity is determine by the number of carbon
Determine by the sequences of the Nitrogenous base atoms
*Catalytic process/processes in the body is possible through the - Contains only Carbon and Hydrogen on its side chain
action of protein - The higher the Hydrogen on its side chain = Higher the
phobicity
BASIC STRUCTURE of AMINO ACIDS a. Mono-amino mono-carboxylic acids
- Simple amino acid- contains C & H on its side
chain
- Branched chain amino acids
- Valine Isoprophyl alcohol side chain
- Leucine Isobutyl side chain
- Isoleucine Contains both
- OH group cntg a.a- OH side chain
- Sulfur cntg a.a- Side chain containing sulfur
- Amide group cntg a.a- Side chain contains amide
group
b. Mono-amino di-carboxylic acids
- Aspartic Acid & Glutamic Acid
c. Di- basic mono-carboxylic acids
- Arginine & Glycine
B. Aromatic Amino acids
- Contains Aromatic Ring on its side chain
Phenylalanine, Tyrosine, Tryptophan
COMMON GROUP C. Heterocyclic Amino acids
N Terminal / Amino group: NH3 - Also contains Cyclic Rings but the ring do not contain
C Terminal Carboxylic group: COO- carbon atom
- It is where new amino acids attach to / end terminal of Tryptophan & Proline
the next amino acid attach to D. Imino acid
Alpha Carbon: C - Same w/ amino acids, it contains both carboxylic and
Alpha Hydrogen: H amino group
R chain / Side Chain / Variable chain Proline
- Identifies specific amino acids E. Derived Amino acids
- Each amino acids have different R chain
Based on side chain characters
HOW TO DIFFERENTIATE AMINO ACID? A. Amino acids with a non-polar side chain
R GROUP - Also hydrophobic (Oily or Lipid like side chain)
VARIABLE GROUP aka SIDE GROUP - Hydrophobic do not bind w/ water and do not give off
Protons
POLYPEPTIDE CHAIN *Hydrogen Proton that is given off or taken off most of the time
Alanine, Valine, Leucine, Isoleucine, tryptophan, Proline,
Phenylalanine, Glycine & Methionine
B. Amino acids with a polar but uncharged side chain
- Uncharged at Neutral Ph
- Hydrophilic (water loving; Gives off Protons)
Glycine, Serine, Theronine, Tyrosine, Cysteine,
Asparginine & Glutamine
C. Amino acids with a charged side chain
o Amino acids with a positively charged side-chain
o Amino acids is designated as Basic Amino Acids
Lycine, Arginine, & Histidine
o Amino acids with a negatively charged side-chain
o Amino acids is designated as Acid Amino acids
Glutamic Acid & Aspartic Acid
o They are hydrophilic in nature (water loving; Gives off
Protons)
AMINO ACIDS
Based on metabolic fate
Classification:
The carbon skeleton of amino acids can be used for glucose
Based on structure
production or for ketone bodies production
Based on side chain characters
 A. Both glucogenic and ketogenic amino acids Maintain the myelin sheaths
Both produces ketone bodies and Glucose Helps manufacture red and white blood cells
Isoleucine, Tyrosine, phenylalanine, & Protects the body from heavy metal toxicity
Tryptophan 2. LEUCINE (Leu)
B. Purely ketogenic amino acids 2nd most common amino acids found in Protein
Releases Ketone Bodies or so called Acetyl-CoA Boosts the healing of muscle, skin, and bones
Leucine & Lysine Lowers blood glucose levels
C. Purely glucogenic amino acids Optimal growth of infants and nitrogen balance
Releases Glucose in adults
By product could be use in the formation of Glucose 3. ISOLEUCINE (Ile)
or Glycogen Maintain, heal, and repair muscle tissue, skin,
Remaining 14 amino acids and bones
Based on nutritional requirements Hemoglobin formation
A. Essential amino acids Regulates blood glucose levels and maintain
Cannot synthesize in the body energy levels
Diet 4. LYSINE ( Lys)
B. Semi-essential amino acids Formation of Collagen Important for the
Can be synthesized in the body but rate of synthesis is production of Connective Tissue, Cartilage &
lesser than the requirement Bones
Arginine & Histidine Production of antibodies and lowers TAG levels
C. Non-essential amino acids Bone development in children
Can be synthesized in the body and absence on the Proper nitrogen balance in adults
diet does not adversely affect the growth of the Absorption and conservation of Calcium
human 5. METHIONINE ( Met )
AUG (genetic code) Initiates translation
AMPHOTERIC PROPERTIES OF AMINO ACIDS process
Same w/ R Proteins Source of sulfur
They can bear either positive or negative charged Breakdown of fats, detoxification of lead and
Formation of Zwitter Ion Amino acids that do not have or is other heavy metals
neutral charged at designated pH (Isoelectric Point) Prevents brittle hair and diminish muscle
Formed when there is Isoelectric Point weakness
Isoelectric Point the pH at which the zwitter ion is It reacts with ATP for synthesis of many
formed important substances
Different in each Amino Acids or Proteins 6. PHENYLALANINE (Phe)
Biosynthesis of other amino acids (Tyrosine &
AMINO ACIDS Homogentisic Acid)
Histidine Interferes in the production of Serotonin in high
Leucine levels
Isoleucine Promotes alertness and vitality
Lysine Decreases pain, aids memory and learning
Methionine Treat arthritis and depression
Phenylalanine Used by brain to produce neurotransmitter
Theronine Interferes with the production of serotonin
Tryptophan Can easily cross the Blood Brain Barrier
Valine Phenylketonuria increase level of
Arginine Phenylalanine in blood and urine
7. THREONINE (Thr)
Alanine Formation of collagen, protein, elastin, and tooth
Aspargine enamel
Aspartic Acid Proper protein balance
Cysteine Aids in liver function, metabolism, and
Glutamine assimilation
Glutamic Acid 8. TRYPTOPHAN (Trp)
Glycine Formed by proteins during digestion
Proline Precursor of serotonin and melatonin
Serine Natural relaxant, alleviating insomnia, soothes
Tyrosine anxiety, and reduces depression
Treatment od migraine headaches, aids in
ESSENTIAL AMINO ACIDS weight control by reducing appetite, helps
1. HISTIDINE (His) control hyperactivity in children
Direct progressor of Histamine important for 9. VALINE (Val)
Allergic or Immune Response together w/ IgE Constituent of fibrous protein in the body
Important source of carbon atoms in the Muscle metabolism and coordination
synthesis of purines Tissue repair, Nitrogen balance
Help grow and repair body tissues Used as energy source
 Treatments for muscle, mental, and emotional
problems
10. ARGININE (Arg)
Often found at the catalytic site (Active site-
where substrate acts to) in proteins and enzymes
Required for UREA generation (Urea Cycle in
Liver)
Synthesis of CREATINE
Ammonia Urea Lesser toxic form that could
be filtered by the Kidney
*Ammonia Toxic to Liver and CNS
NON-ESSENTIAL AMINO ACIDS
1. ALANINE (Ala)
One of the simplest
Energy-producing breakdown of glucose
Product of DNA or dipeptides breakdown
Major role in:
Transfer of Nitrogen from peripheral
tissue to liver
Reducing the build up of toxic
substances
Strengthens the immune system
2. ASPARAGINE (Asn)
First amino acid to be isolated in Asparagus Juice
Principal and most abundant a.a involved in
Nitrogen transport
Beta amide of aspartic acid
Main function: Converting Amino acid into
another by amination and trans amination
Amination adding amide group in one
amino acid
Trans amination- one amino group is
being transferred by alpha ketone acid
Important for synthesis of Ammonia
3. ASPARTIC ACID (Asp)
Vital role in metabolism during construction of
other amino acids and metabolites in the citric
acid cycle
A metabolite in the urea cycle
Participates in gluconeogenesis
4. CYSTEINE (Cys)
Only amino acid that contains sulfur
Potentially toxic and catabolized in the GIT and
blood
Used as constituent in the food, pharmaceutical,
and personal care industries
Production of flavors
5. GLUTAMIC ACID (Glu)
Glutamic acid plus an amino group= Glutamine
Serves as neurotransmitter
Metabolism of sugars and fats and aids in
transporting potassium into CSF
Food additive and flavor enhancer
6. GLUTAMINE (Gln)
Most abundant amino acid
Converted to glucose for energy and aids in
immune function
Assists in proper ACID/ALKALINE balance
Basis of the building blocks for the synthesis of
RNA and DNA
Transport ammonia to the liver
High concentration in skeletal muscles
7. GLYCINE (Gly)
Simplest but not optically active
Essential for synthesis of: nucleic acids, bile
acids, proteins, peptides, purines, ATP,
porphyrins, hemoglobin
Used by the liver for detoxification of
compounds
Inhibitory neurotransmitter in the CNS
Metal complexing agent, retards muscle
degeneration, improves glycogen storage, and
promotes healing
8. PROLINE (Pro)
Precursor of hydroxyproline
Molecular recognition
Important component in certain medical wound
dressings
Works with Vitamin C to promote healthy
connective tissues
Healing of cartilage
9. SERINE (Ser)
2ND amino acid that is also an alcohol
Important role: Bodys synthetic pathways for
pyrimidines, purines, creatine, and porphyrins
Component of the protectibe myelin sheath
Aids in production of immunoglobulins and
antibodies
10. TYROSINE (Tyr)
Synthesized from phenylalanine
Precursor of the adrenal hormones
Important for overall metabolism, aiding in the
functions of the adrenal, thyroid, and pituitary
gland
Acts as mood elevator, suppressing appetite and
helps reduce body fats
Two New Amino Acids
A. SELENOCYSTEINE (Sec)
21st Amino acid
Not coded for directly in the genetic code
UGA codon (stop codon)
Selenium analogue of cysteine
Same structure as cysteine except that the sulfur
side chain is changed w/ selenium
Present in different enzymes of the body
Higher amount in HIV1
B. PYRROLYSINE (Pyl)
Used by Archea (prokaryotes)
Encoded by UAG (stop codon)
Same w/ Lysine but pyrrolysine contains the so
called Pyrrol group
AMINOACIDOPATHIES c. Type III tyrosinemia- 4-Hydroxyphenylpyruvate
Class of inherited errors of amino acid metabolism Dioxygenase
Enzymes are defective that inhibits the bodys ability to Accompanied by elevated methionine and p-
metabolize certain amino acids hydroxyphenylpyruvic acid in blood
Abnormality: Clinical features: Liver damage or Cirrhossis, Kidney
Metabolic pathway damage and rickets (bones)
Membrane transport system (Cystinuria)
Type of Signs and Symptoms
Aminoacidopathies
Tyrosinemia
1. Phenylketonuria
Autosomal recessive trait / Genetically inherited Type I Failure to thrive, diarrhea, vomiting, jaundice,
Enzyme deficient: Phenylalanine Hydroxylase /
bleeding, swelling of legs, cabbage like odor
Phenylalanine
Liver and kidney failure, cirrhosis or liver cancer
monooxygenase
later in life
Phenylalanine to Tyrosine
Prime metabolite: Phenylpyruvic acid Type II Mental retardation, excessive tearing,
(+) Urine and Blood in elevated photophobia, eye pain and redness, painful skin
concentration lesions
Reference value for serum phenylalanine:
Adult: 1.2-3.4 mg/dL or 70-200 mmol/L Type III Mild mental retardation, seizures, periodic loss of
Newborn: 2 mg/dL or 120 mmol/L balance and coordination
First that is being incorporated to newborn
screening
Clinical features: retarded mental development
(infants and children) & Microcephaly
Diagnostic indicators: Musty or Mousy urine odor
>1200 umol/L: Phenylketonuria
600-1200 umol/L: mild phenylketonuria
180-600 umol/L: non PKU or
HYPERPHENYLALANINEMIA- due to problem on the
TetraHydroBiopterin (BH4 important for aromatic
hydroxylation of aromatic amino acids)
Screening test:
GUTHRIE Test- most well known blood
test for PKU
Bacillus subtilis is used w/
2thienylalanine as its antagonist
(+) Bacterial growth of >4mg/dL
Confirmatory Test:
HPLC
MS/MS 3. Alkaptonuria
GC/MS Inborn metabolic disease transmitted as an
Treatment: Cuvan only enhances activity of PAH autosomal recessive gene, the HGD gene
Deficient enzyme: Homogentisate Oxidase
Clinical feature: Occronosis (Tissue pigmentation) in
the sclera, cartilage and bones
Diagnostic indicator: Darkening of urine
Brownish to black, accumulation of
homogentisic acid (HGA)
Test: Ferric Chloride test
Drop of Ferric chloride in urine: (+) Black urine
Treatment: High dose Vitamin C

4. Maple Syrup Urine Disease

Phenylalanine through the action of Phenylalanine
Hydroxylase (PAH) will be producing Tyrosine. But w/out
PAH, it can lead to Phenylketonuria
2. Tyrosinemia
Enzyme deficient: depends on the type of
tyrosinemia
Three types: (Enzyme deficient)
a. Type I tyrosinemia- fumarylacetoacetate hydrolase
b. Type II tyrosinemia- tyrosine aminotransferase
Autosomal recessive trait
Enzyme reduced or absent: Alpha KetoAcid
decarboxylase
Results to accumulation of branched chain amino
acids
Leucine, Isoleucine, and Valine
4mg/dL of leucine is indicative of MSUD
Clinical features: Failure to thrive, mental retardation,
Hypoglycemia, muscular rigidity
Diagnostic indicator: Burnt sugar urine odor
 Most striking feature: Maple syrup odor of urine Defect in the amino acid transport system not an
breath and skin enzyme deficiency
Screening test: Modified Guthrie Test Main Problem: Reabsorption process
Inhibitor: 4 ASA Leucine 2 modes of inheritance
Diagnostic test: Amino acid analysis (HPLC) 4 amino acids: cystine, lysine, arginine, and
MS/MS ornithine are not reabsorbed
Only cystine and lysine are not reabsorbed
5. Isovaleric Acidemia Screening test: Cyanide-Nitroprusside test
Autosomal recessive disorder (+) Red Purple
Enzyme deficient: Isovaleryl-CoA Dehydrogenase
Clinical features: failure to thrive, vomiting. Lethargy, AMINO ACID ANALYSIS
seizures, coma, death Atleast 6-8 hours fasting (False inc. if not followed)
Diagnostic indicator: Sweaty Feet odor of urine Heparinized tube
Test: MS/MS or chromatography Plasma sample- do not get the Buffy Coat (Cause False
Asymptomatic if there is gene mutation Increased due to WBC containing Aspartic and Glutamic Acid)
Deproteinization should be done within 30 minutes of sample
6. Homocystinuria collection
Inherited autosomal disorder Test performed immediately or if not possible frozen at -20C
Impaired activity of cystathionine beta synthetase or -40C
Results to elevated levels of homocysteine and Sample:
methionine in blood and urine Urine- random collection or 24 hr. Urine sample preserve
Clinical features: physical defects, thrombosis, w/ Thymol
osteoporosis, eye lens abnormality, mental Serum most preferred than plasma
retardation, bone weakening and thinning Amniotic fluid
Screening test: Modified Guthrie test
Antagonist/Inhibitor: L-Methionine Sulfoximine Screening test
MS/MS Thin Layer Chromatography- method of choice
LC-MS/MS Ion exchange chromatography
MS/MS- highly specific and sensitive method for amino
7. Citrullinemia acid measurement
Belong to Urea Cycle disorders
Inherited autosomal recessive disease
Types:
a. Type 1 cittrulinemia- enzyme deficiency
Build up of citrulline and ammonia in
blood
Lack of appetite, failure to thrive,
ammonia build up
Brain damage or death
b. Type II citrullinemia- Gene mutation
Cells are prevented on making citrin
Inhibits urea cycle and disrupts
protein and nucleotide
production
Build up of ammonia and other toxic
substances
Citrin- important for the transfer of the molecules
into the cell

8. Argininosuccinic Aciduria
Inherited autosomal recessive disease
Enzyme deficient: Argininosuccinic acid lyase (ASL)
Preventing the conversion of
argininosuccinic acid to arginine
Urea cycle cannot proceed, Nitrogen
accumulates in blood in the form of
ammonia
Causes build up of citrulline in blood
Clinical feature: CNS and Liver damage

9. Cystinuria
Inherited autosomal recessive defect
AMINOACIDOPATHY DEFICIENT ENZYME CLINICAL FEATURE

TYROSINEMIA I Failure to thrive, jaundice,

cabbage like odor

II Mental retardation,
photophobia

III Seizures, periodic loss of

balance and coordination

CITRULLINEMIA I Lack of appetite, failure to

thrive, vomiting , lethargy

II Affects nervous system

ARGINOSUCCINIC Unwillingness to eat,

ACIDURIA lethargy

CYSTINURIA Hematuria, UTI, pain in the

side (kidney pain)