Amino Acid Metabolism

🟢 Lite — Quick Review (1h–1d)

Rapid summary for last-minute revision before your exam.

Amino acid metabolism covers how the body handles the amino group (N) and the carbon skeleton (C) separately. Transamination shuffles –NH₂ between amino acids using pyridoxal phosphate (PLP), without releasing free ammonia. Oxidative deamination by glutamate dehydrogenase (GDH) liberates NH₄⁺ from glutamate for urea synthesis. Nitrogen is detoxified through the urea cycle (2 NH₃ + CO₂ → urea) in the liver; carbon skeletons enter the TCA cycle as glucogenic or ketogenic intermediates.

Purely ketogenic: Leu, Lys
Both glucogenic + ketogenic: Ile, Phe, Trp, Tyr
Essential amino acids (9): His, Ile, Leu, Lys, Met, Phe, Thr, Trp, Val

🟡 Standard — Regular Study (2d–2mo)

Standard content for students with a few days to months.

Transamination vs oxidative deamination

Transaminases (ALT, AST) catalyse reversible amino-group transfer using PLP as a Schiff-base intermediate. The reaction is: Amino acid₁ + α-keto acid₂ ↔ Amino acid₂ + α-keto acid₁. No free NH₄⁺ is produced, which is why ALT/AST elevation in hepatitis does not cause hyperammonaemia. GDH performs true oxidative deamination: α-ketoglutarate + NH₄⁺ + NAD(P)H → glutamate + NAD(P)⁺ + H₂O. It is the only enzyme that fixes inorganic ammonia onto a carbon skeleton and is allosterically activated by ADP and inhibited by GTP.

Classification of carbon skeletons

Entry point	TCA intermediate	Examples
Glucogenic → pyruvate	Pyruvate	Ala, Ser, Gly, Cys, Thr
Glucogenic → α-KG/succinyl-CoA/OAA/fumarate	TCA intermediates	Glu, Gln, Asp, Asn, Arg, His, Pro, Val, Met, Ile
Ketogenic → acetyl-CoA/acetoacetate	Acetyl-CoA	Leu, Lys
Both (glucogenic + ketogenic)	Mixed	Ile, Phe, Trp, Tyr

Urea cycle enzymology

The cycle runs partly in mitochondria (CPS-I, OTC) and partly in cytosol (ASS, ASL, arginase). CPS-I is the committed, rate-limiting step, requires N-acetylglutamate (NAG) as an essential allosteric activator, and hydrolyses 2 ATP. The full stoichiometry: 2 NH₃ + CO₂ + 3 ATP + aspartate → urea + fumarate + 2 ADP + AMP + 4 Pi (net ≈ 3 high-energy phosphates per urea). Ornithine and citrulline are the two carrier amino acids.

Hyperammonaemia therapy: sodium benzoate + sodium phenylacetate/phenylbutyrate provide alternative N excretion pathways (hippurate + phenylacetylglutamine).
N-acetylglutamate synthase deficiency mimics CPS-I deficiency and is treated with N-carbamylglutamate (carglumic acid).
AST also feeds nitrogen into the urea cycle by generating aspartate, the second donor of the ureido group.

🔴 Extended — Deep Study (3mo+)

Comprehensive coverage for students on a longer study timeline.

One-carbon metabolism and SAM

S-adenosylmethionine (SAM) is the universal methyl donor. The methionine cycle regenerates methionine via the B12-dependent enzyme methionine synthase (MS), which transfers a methyl group from 5-methyl-THF to homocysteine. SAM → SAH + methyl group (Km of MAT ≈ 10 µM). Methylation reactions (DNA, histones, neurotransmitters, phospholipids) consume SAM and produce S-adenosylhomocysteine (SAH), a potent inhibitor of methyltransferases. Folate cycle interlinks with this pathway, making B12 and folate deficiencies clinically inseparable in causing megaloblastic anaemia.

Inborn errors of amino acid metabolism (NEET PG favourites)

Disorder	Enzyme defect	Accumulating substrate	Clinical clue
Phenylketonuria	Phenylalanine hydroxylase (or BH₄)	Phenylalanine	Mousy body odour, eczema, intellectual disability
Maple syrup urine disease	Branched-chain α-keto acid dehydrogenase (BCKDH)	Leu/Ile/Val	Sweet-smelling urine in neonates
Alkaptonuria	Homogentisate oxidase	Homogentisic acid	Black urine, ochronosis
Homocystinuria	Cystathionine β-synthase	Homocysteine	Lens dislocation (downward), Marfanoid habitus, thrombosis
Albinism	Tyrosinase	Melanin precursors	Hypopigmented skin, hair, eyes
Non-ketotic hyperglycinaemia	Glycine cleavage system	Glycine	Neonatal seizures

Worked micro-example

A patient with elevated phenylalanine and normal tyrosine but reduced urinary biopterin has DHPR deficiency (a BH₄ recycling defect). Treatment includes BH₄ (sapropterin) supplementation plus a low-Phe diet.

Common exam traps

Phe is BOTH glucogenic and ketogenic (acetoacetate + fumarate) — never mark it as purely ketogenic.
GDH cofactor is dual: NADH (catabolic direction) or NADPH (anabolic direction) — examiners test the reversibility.
CPS-I vs CPS-II: CPS-I is mitochondrial and urea-specific; CPS-II is cytosolic and makes pyrimidines. Do not confuse.
ALT ≠ urea-cycle enzyme: ALT elevation signals hepatocellular injury, not ammonia handling failure.

Practice prompts

Explain how a block at argininosuccinate synthetase produces hyperammonaemia even though arginine accumulates.
Why is leucine uniquely ketogenic and unable to yield net glucose?

Continue your study

View this topic in your NEET PG roadmap — see where “Amino Acid Metabolism” fits in your personalised plan
Build a quick revision plan — 1-day sprint covering highest-weight topics
NEET PG exam overview — pattern, eligibility, and syllabus
All Biochemistry notes — browse sibling topics in this subject

Content adapted based on your selected roadmap duration. Switch tiers using the selector above.

Amino Acid Metabolism