Amino Acids

BIOCHEMISTRY
Amino Acid Catabolism: Urea Cycle & its Disorders

Protein when become excess in the human body is degraded and excreted in the form of non-toxic urea.

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UREA SYNTHESIS

1. Transamination
The process of transfer of amino acid (AA) group from 1 Amino acid to α -keto acid
Lysine
Proline Do not undergo
Threonine Transamination

2. Oxidative Deamination:
Site: Mitochondrial matrix of liver cell
Enzyme: Glutamate dehydrogenase (GDH)

Regulation

Leucine Causes Hypoglycemia (↑ATP - ↑Insulin Release)

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3. Urea Cycle:
Site - Mitochondria & Cytoplasm of Liver cell

(Ornithine recycled via ORNT1)

Link of TCA & Urea Cycle: (OAA to aspartate in presence of AST)
AST
Fumarate Malate Oxaloacetate Aspartate

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Regulation:

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UREA CYCLE DISORDERS

1. Type I Hyperammonemia:
Deficiency of CPS –I or NAG
Investigation:
• Severe ammonia toxicity (NH3), or
• High Glutamine (Marker of ammonia levels)

Excess ammonia binds to α-Ketoglutarate of the brain also, thus there is reduced ATP synthesis. Hence NH3
is toxic.
In Brain:

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2. Type II Hyperammonemia:
X-linked recessive > X-linked dominant
Most common disorder
OTC is deficients
Investigation:
• ↑NH3 or ↑Glutamine
• Orotic aciduria or ↑Uracil
Since, orotic acid needs sugar & phosphate to convert into
uracil which is limited due to limited HMP shunt, the pathway usually stops at orotic acid.

3. Citrullinemia:
Arginosuccinate Synthetase deficient
Investigation: i. ↑ NH3
ii. ↑ Citrulline
4. Arginosuccinic Aciduria:
Arginosuccinic Lyase deficient
Investigation: i. ↑ NH3
ii. ↑ Citrulline
iii. ↑ Arginosuccinate
Clinical feature: Trichorrhexis Nodusa
5. Hyperarginenemia:
Arginase deficient
No NH3 toxicity till 2-3 years
Presents at 3 years of age with Spastic Diplegia
Investigation:
• COLA in urine/ Cystine-Lysinuria (C–Cystine, O–Ornithine, L–Lysine, A–Arginine)
• ↑ Arginine
6. HHH Syndrome:
Deficiency of ORNT – 1

Defect Enzyme Deficient

Hyper-
Type I Hyperammonemia CPS-I or NAG ammonemia
Type II Hyperammonemia Ornithine transcarbomylase (OTC)
Citrullinemia Arginosuccinate Synthetase
Arginosuccinic aciduria Arginosuccinic Lyase
Hyper-
Hyperargeninemia Arginase Homocitrulinemia
ornithinemia
HHH Syndrome ORNT-1

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MANAGEMENT OF UREA ACID CYCLE DISORDER

1. Low protein & High Carbohydrate diet

2. Arginine Supplement except in Hyperargininemia
3. Drugs (Ammonia Scavengers)
Phenylbutyrate (This prodrug is activated to phenylacetate with a mousy odour similar to Phenyl
Ketouria)

Nitrogen
Phenyl Phenylacetate PA binds to Phenyl-acetyl
s containing
Butyrate (PA) Glutamine glutamine(2N)
urine appears

Benzoic Acid

This non-toxic
Benzoic Acid bind to Convert to Hippuric
substance appear in
Glycine (1N) acid
urine

4. Haemodialysis

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