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Simplest amino acid
H–CH₂–COOH
No chiral carbon
Both glucogenic & non-essential
From serine
Serine → glycine (via serine hydroxymethyltransferase, requires PLP & THF)
From threonine (minor pathway)
Component of collagen (1 in every 3 residues = glycine)
Required for heme synthesis (glycine + succinyl-CoA → δ-ALA)
Required for glutathione synthesis
Precursor of purines
Component of bile salts (glycocholate)
Neurotransmitter (inhibitory) in spinal cord
Defects in glycine cleavage → non-ketotic hyperglycinemia
Severe neonatal seizures
↑ CSF glycine
“Glycine encephalopathy”
A nitrogenous compound present mainly in muscle & brain; stores high-energy phosphate.
Occurs in kidney + liver:
Arginine + glycine → guanidinoacetate
(Kidney)
Guanidinoacetate → creatine
(Liver; requires SAM)
Creatine travels to muscle, where it is phosphorylated:
Creatine + ATP → Phosphocreatine
Enzyme: Creatine kinase (CK)
Rapid energy buffer in muscle
Helps regenerate ATP during contraction
Used clinically to assess muscle injury (CK leaks into blood)
A cyclic spontaneous breakdown product of creatine and phosphocreatine.
Produced at a constant rate
Proportional to muscle mass
Freely filtered by kidney
Not reabsorbed → excellent marker of GFR
Best routine blood test for GFR
High creatinine = kidney dysfunction
Creatinine clearance = estimate of GFR
A group of genetic disorders where excess oxalate is produced → kidney stones, renal failure.
Type I
Defect: Alanine–glyoxylate aminotransferase (AGT)
Glyoxylate → oxalate
Most severe
Type II
Glyoxylate reductase deficiency
Type III
HOGA1 deficiency
Early-onset calcium oxalate stones
Nephrocalcinosis
Progressive renal failure
High urinary oxalate
Normally:
Glycine ↔ glyoxylate
Glyoxylate is detoxified to glycine
In disease:
Glyoxylate → oxalate
Oxalate forms stones (insoluble)
Hydroxy amino acid
Polar, uncharged
Precursor of glycine
From 3-phosphoglycerate (glycolysis intermediate)
Donor of one-carbon units (via conversion to glycine)
Essential for phosphatidylserine synthesis
Component of sphingolipids
Required for folate-dependent pathways
Serine → pyruvate (gluconeogenic)
Cancer cells up-regulate serine synthesis for rapid nucleotide production.
(This is sometimes called the one-carbon exchange between serine, glycine & choline.)
To generate one-carbon units and maintain methylation reactions.
Via serine hydroxymethyltransferase
Produces methylene-THF
Betaine donates a methyl group to homocysteine → methionine
Maintains SAM cycle
Reversible conversion
Supports THF cycle
Generates one-carbon units
Major supplier of one-carbon units for DNA synthesis
Links amino acid & methylation metabolism
Crucial during pregnancy, growth, cancer cell proliferation
Known as the 21st amino acid.
Similar to cysteine but sulfur is replaced by selenium.
Incorporated during translation, not post-translationally.
Coded by the UGA codon, which normally signals stop.
Presence of a special SECIS element (Selenocysteine Insertion Sequence) in mRNA allows recoding of UGA → selenocysteine.
Requires a dedicated tRNA-Sec.
Present in several antioxidant enzymes:
Glutathione peroxidase
Thioredoxin reductase
Iodothyronine deiodinases (thyroid hormone activation)
Selenium deficiency → ↓ glutathione peroxidase → oxidative stress.
Seen in TPN without selenium supplementation.
Non-essential amino acid
Formed mainly by transamination:
Pyruvate + glutamate → alanine + α-ketoglutarate
Carrier of nitrogen from muscle → liver
Important in fasting and exercise
Component of the glucose–alanine cycle
Amino group disposal (safely transported as alanine)
ALT (Alanine transaminase) is a sensitive marker of liver cell injury.
Transport nitrogen from muscle → liver
Provide glucose back to muscle
Prevent toxic ammonia buildup in muscle
Amino acids → lose NH₂ → form glutamate
Glutamate transfers NH₂ to pyruvate → alanine
Alanine travels to liver
Alanine → pyruvate + NH₃
NH₃ → urea cycle
Pyruvate → glucose (via gluconeogenesis)
Glucose returns to muscle
Active in fasting, exercise, catabolic states
Clears nitrogen safely
Provides energy substrate to muscle
β-isomer of alanine
Not used in protein synthesis
Formed from uracil degradation
Component of:
Coenzyme A (CoA)
Carnosine (muscle buffer)
Pantothenic acid (Vitamin B5)
Beta-alanine supplementation increases carnosine, improving muscle buffering.
Essential amino acid
Both glucogenic & ketogenic
Threonine can be metabolized via three pathways:
Involves threonine aldolase
Leads to succinyl-CoA
Vitamin B12 dependent
Important glucogenic route
Via threonine dehydratase
Component of mucins (O-linked glycosylation)
Required for one-carbon metabolism (via conversion to glycine)
Supports gut immunity
Threonine deficiency → poor mucin production → impaired intestinal barrier function.
Selenocysteine → encoded by UGA; in glutathione peroxidase.
Alanine → primary nitrogen carrier from muscle to liver.
Glucose–Alanine cycle → runs in fasting; prevents ammonia buildup in muscle.
Beta-alanine → part of CoA & carnosine.
Threonine → essential; forms glycine and propionyl-CoA.
Essential amino acid
Sulfur-containing
Precursor of S-adenosylmethionine (SAM) — the universal methyl donor
Both glucogenic and ketogenic
Methyl group donor (via SAM)
Precursor of cysteine
Required for synthesis of:
Carnitine
Creatine
Adrenaline
Phosphatidylcholine (lecithin)
Polyamines
DNA/RNA methylation
Methionine → SAM
(via methionine adenosyltransferase)
SAM → SAH (S-adenosylhomocysteine)
(after donating methyl groups)
SAH → Homocysteine
Homocysteine has 2 fates:
Remethylation to methionine
(Requires folate + B12)
Transsulfuration to cysteine
(Requires vitamin B6)
SAM has high-energy sulfonium bond
Donates CH₃ group to various acceptors
Norepinephrine → Epinephrine
Phosphatidylethanolamine → Phosphatidylcholine
Guanidinoacetate → Creatine
DNA methylation (epigenetics)
RNA methylation
Melatonin synthesis
Carnitine synthesis
Homocysteine + methyl-THF → methionine
Enzyme: Methionine synthase
Cofactor: Vitamin B₁₂
Folate or B12 deficiency → ↑ homocysteine
Hyperhomocysteinemia → cardiovascular risk
Sulfur-containing amino acid
Non-essential, but depends on methionine → “semi-essential”
Precursor of glutathione
From methionine → homocysteine → cystathionine → cysteine
Requires Vitamin B6 (PLP)
Component of glutathione
Required for coenzyme A synthesis
Part of disulfide bonds → stabilizes protein tertiary structure
Precursor of taurine (bile salts)
Detoxification reactions
Defect in cystathionine β-synthase → homocystinuria
High homocysteine
Lens dislocation, thrombosis, developmental delay
A tripeptide:
Glutamate – Cysteine – Glycine
Major intracellular antioxidant
Neutralizes H₂O₂ (via glutathione peroxidase)
Regenerated by glutathione reductase (uses NADPH)
Maintains RBC membrane integrity
Required for:
Transport of amino acids (γ-glutamyl cycle)
Detoxification (conjugation reactions)
Leukotriene synthesis
Protection against oxidative drugs (e.g., sulfonamides)
Deficiency → hemolysis
Glutathione peroxidase contains selenocysteine
NADPH (from HMP shunt) is necessary to maintain GSH in reduced form
Sulfur-containing amino acids:
Methionine
Cysteine
Diet: onions, garlic, pulses
Taurine needed for taurocholic acid (bile salt)
Requires cysteine for the thiol (–SH) group
Essential antioxidant
Detoxification in liver (phase II reactions)
Inactivation of hormones (e.g., catecholamines)
Sulfated steroids, bile acids
Sulfate is excreted as inorganic sulfate in urine
Defect in cystathionine synthase → accumulation of homocysteine
Vitamin B6 deficiency → impaired cysteine synthesis
High sulfur intake → odor in urine (benign)
Methionine → SAM → methyl transfer → homocysteine → cysteine.
SAM is the universal methyl donor.
Cysteine is non-essential but methionine-dependent.
Glutathione = glutamate + cysteine + glycine.
Glutathione peroxidase contains selenocysteine.
Sulfur used in glutathione, CoA, taurine, detoxification.
Homocystinuria = CBS deficiency, requires B6.
A hereditary disorder of renal reabsorption of dibasic amino acids.
Defective transporter for:
Cystine
Ornithine
Lysine
Arginine
(remember: COLA)
Cystine is least soluble → forms hexagonal crystals
Leads to recurrent kidney stones
Flank pain
Hematuria
Recurrent cystine stones
Stones begin in childhood or adolescence
Urine microscopy → hexagonal cystine crystals
Cyanide–nitroprusside test positive
High fluid intake
Urinary alkalinization (potassium citrate)
Penicillamine in severe cases → forms soluble complexes
Homocysteine is an intermediate between methionine and cysteine.
Defects in its metabolism → homocystinuria.
Most common.
Cystathionine β-synthase (CBS) deficiency.
Vitamin B6 (PLP) as cofactor
Some patients respond to high-dose B6
Methionine ↑
Homocysteine ↑↑
Cystathionine ↓
Cysteine ↓ (becomes essential)
Very similar to Marfan syndrome but with thrombosis:
Tall, long limbs
Intellectual disability
Downward lens dislocation (Marfan → upward)
Osteoporosis
Thromboembolism (most dangerous)
High-dose B6
Restrict methionine
Supplement cysteine
Betaine (donates methyl groups → remethylates homocysteine)
Impaired conversion of
Homocysteine → Methionine
due to lack of B12-dependent methionine synthase activity.
Homocysteine ↑
Methionine ↓
Methylmalonic acid normal
Megaloblastic anemia
Developmental delay
Homocysteine accumulation
Reduced conversion of methyl-THF → impaired homocysteine remethylation.
Homocysteine ↑
Methionine ↓
Methylmalonic acid normal
Neurological problems
Megaloblastic changes
| Type | Enzyme Defect | Methionine | Homocysteine | Key Feature |
|---|---|---|---|---|
| Type I | CBS | ↑ | ↑↑ | Lens dislocation, thrombosis |
| Type II | Methionine synthase | ↓ | ↑ | Megaloblastic anemia |
| Type III | MTHFR | ↓ | ↑ | Neuro symptoms |
Rare defect in cystathionine γ-lyase, the enzyme that converts:
Cystathionine → Cysteine + α-ketobutyrate
Cystathionine ↑↑ in blood and urine
Homocysteine normal or mildly ↑
Cysteine ↓ (may become conditionally essential)
Most cases are benign and asymptomatic.
Occasionally mild developmental delay or growth issues.
Low vitamin B6
Premature birth
Liver disease
Vitamin B6 supplementation
No strict diet needed (unlike homocystinuria)
Cystinuria: COLA transport defect → cystine stones → hexagonal crystals.
Homocystinuria Type I: CBS deficiency → methionine ↑ → downward lens dislocation + thrombosis.
Type II & III: Remethylation defects → methionine ↓ + megaloblastic features.
Cystathioninuria: Cystathionine γ-lyase deficiency → benign, B6 responsive.
Simplest amino acid; no chiral carbon.
Major component of collagen (every third residue).
Required for heme synthesis (glycine + succinyl-CoA → δ-ALA).
Part of glutathione and purine rings.
Inhibitory neurotransmitter in spinal cord.
Defect in glycine cleavage → non-ketotic hyperglycinemia (seizures, ↑ CSF glycine).
Creatine synthesized from arginine + glycine, methylated by SAM.
Converted in muscle to phosphocreatine (energy reservoir).
Creatinine is spontaneous breakdown product → marker of GFR (constant rate).
Due to defect in alanine–glyoxylate aminotransferase (type I).
Excess oxalate → calcium oxalate stones, nephrocalcinosis, renal failure.
Glyoxylate diverted → oxalate (instead of → glycine).
Synthesized from 3-phosphoglycerate.
Major donor of one-carbon units (via conversion to glycine).
Precursor of phosphatidylserine and sphingolipids.
Serine hydroxymethyltransferase requires PLP + THF.
Central route for generating one-carbon units.
Choline → betaine → donates methyl group to homocysteine → methionine.
Important for DNA synthesis and methylation balance.
Main amino acid released by muscle during fasting.
Major carrier of nitrogen from muscle → liver.
Formed by transamination of pyruvate (ALT).
Part of the glucose–alanine cycle.
Muscle forms alanine to transport NH₂ safely.
Liver converts alanine → pyruvate + NH₃ → urea.
Pyruvate → glucose → back to muscle.
Active in exercise and fasting.
Component of Coenzyme A and pantothenic acid.
NOT used in proteins.
Formed from uracil degradation.
Essential amino acid.
Both glucogenic and ketogenic.
Converted to glycine, acetaldehyde, propionyl-CoA.
Important in mucin proteins (O-glycosylation).
Essential sulfur amino acid.
Precursor of SAM (universal methyl donor).
Converted to homocysteine, which either:
Remethylates to methionine (B₁₂ + folate), or
Enters transsulfuration to cysteine (B₆).
SAM donates methyl group for:
Epinephrine synthesis (from norepinephrine)
Creatine synthesis
Phosphatidylcholine formation
DNA & RNA methylation
Melatonin synthesis
Carnitine synthesis
SAM → SAH → homocysteine → methionine (requires B12).
Requires B6, B12, folate.
High homocysteine → thrombosis, endothelial injury.
Classical homocystinuria (CBS deficiency): methionine ↑, lens dislocation (downward), thrombosis.
Formed from homocysteine + serine (requires B6).
“Semi-essential” — dependent on methionine.
Precursor of:
Glutathione
Coenzyme A
Taurine (for bile salts)
Disulfide bonds (protein structure)
21st amino acid.
Encoded by UGA (normally a stop codon).
Requires SECIS element in mRNA.
Present in key antioxidant enzymes:
Glutathione peroxidase
Thioredoxin reductase
Iodothyronine deiodinase (T₄ → T₃)
Tripeptide: Glu–Cys–Gly.
Most important intracellular antioxidant.
Detoxifies H₂O₂ (glutathione peroxidase + selenium).
Regenerated by glutathione reductase using NADPH (from HMP shunt).
Protects RBCs from oxidative damage.
Essential in drug detoxification.
Sulfur comes from methionine & cysteine.
Used in:
Glutathione
CoA
Taurine (bile salts)
Detoxification (sulfation)
Excreted as inorganic sulfate.
Defect in renal reabsorption of COLA amino acids (Cystine, Ornithine, Lysine, Arginine).
Leads to cystine stones → hexagonal crystals.
Type I (CBS deficiency) → methionine ↑, homocysteine ↑↑
Type II (B12 defect) → methionine ↓
Type III (MTHFR defect) → methionine ↓
Classical presentation: thrombosis + downward lens dislocation.
Defect of cystathionine γ-lyase.
Usually benign, B6 responsive.
Glycine: heme, collagen, glutathione, purines.
Serine ↔ glycine → one-carbon units.
Alanine: nitrogen carrier; glucose–alanine cycle.
Methionine → SAM → methyl transfer → homocysteine → cysteine.
Cysteine: precursor of glutathione, CoA, taurine.
Selenocysteine: antioxidant enzymes, coded by UGA.
Glutathione: antioxidant; uses NADPH.
Cystinuria: COLA defect, hexagonal stones.
Homocystinuria: CBS deficiency → thrombosis + lens dislocation.
A newborn within 24 hours of life develops intractable seizures, apnea, and hypotonia.
Investigations:
Very high CSF glycine
Serum glycine mildly elevated
Normal ketones
Non-ketotic hyperglycinemia
Defect in glycine cleavage enzyme → glycine accumulates in CSF → severe encephalopathy.
A 15-year-old presents with flank pain.
Urinalysis shows hexagonal, flat crystals.
Family history positive for renal stones.
Cystinuria
Defect in renal tubular reabsorption of COLA amino acids.
Cystine is poorly soluble → stone formation.
A young athlete collapses after marathon running.
Blood shows:
CK extremely high
Creatinine mildly elevated
Myoglobinuria present
Rhabdomyolysis
Creatine/phosphocreatine breakdown → increased creatinine; CK leaks from damaged muscle.
A 3-year-old has recurrent kidney stones.
Urinary oxalate extremely high.
Renal biopsy shows oxalate deposition.
Primary hyperoxaluria (Type I)
Defect in alanine–glyoxylate aminotransferase → glyoxylate → oxalate.
A chronic alcoholic with normal AST/ALT but very high GGT.
GGT elevation due to induction of γ-glutamyl cycle enzymes
GGT participates in the Meister cycle for amino acid transport.
A 14-year-old tall, thin boy with long limbs, intellectual disability, and downward lens dislocation.
There is history of recurrent DVT.
Classical Homocystinuria (CBS deficiency)
Methionine ↑
Homocysteine ↑↑
Cysteine ↓
A 22-year-old vegetarian female has:
Macrocytic anemia
Very high plasma homocysteine
Normal methylmalonic acid
No neurologic symptoms
Folate deficiency or impaired remethylation (Type II Homocystinuria)
Remethylation requires folate + B12; MMA normal → not B12 deficiency.
A 6-month-old child has failure to thrive, hepatomegaly, and delayed milestones.
Plasma: Methionine ↑, Homocysteine ↑↑, Cystine ↓.
Homocystinuria (CBS deficiency)
A child evaluated for urinary amino acids shows markedly elevated cystathionine, but normal development and no vascular events.
Cystathioninuria (cystathionine γ-lyase deficiency)
Usually benign, B6 dependent.
A patient treated with sulfonamides develops jaundice and anemia.
Peripheral smear shows bite cells.
Glutathione deficiency–induced hemolysis
Drugs generate oxidative stress.
Glutathione protects RBCs.
G6PD deficiency can worsen it.
A patient on long-term parenteral nutrition develops fatigue, bradycardia, and mild goiter despite normal TSH.
Biochemistry shows low T3.
Selenium deficiency → low selenocysteine-dependent deiodinase activity
Selenocysteine is essential for 5’-deiodinase (T4 → T3).
A bodybuilder reports fatigue during high-intensity exercise but improves after taking beta-alanine supplements.
Improved carnosine levels (a muscle buffer).
A newborn with lethargy and seizures shows elevated sulfite in urine.
Sulfite oxidase deficiency
Inability to convert sulfite → sulfate; sulfur amino acid catabolism disturbed.
A patient with poor nutrition and alcoholism has low cysteine levels, fatigue, and oxidative stress.
Reduced transsulfuration due to B6 deficiency
Cystathionine β-synthase and γ-lyase require B6.
Tumor biopsy shows extremely high demand for serine and glycine.
Tumor relies on serine–glycine one-carbon metabolism for nucleotide synthesis.
Homocysteine is very high, methionine is low, methylmalonic acid is normal.
Type III homocystinuria — MTHFR deficiency
A patient with overdose shows liver enzyme elevation.
Glutathione levels are extremely low.
Glutathione depletion leading to hepatotoxicity
(Treatment = N-acetylcysteine)
Labs show:
Homocysteine ↑
Methylmalonic acid ↑
Methionine ↓
Vitamin B12 deficiency
Both remethylation and methylmalonyl-CoA pathway affected.
Tracing reveals low glutathione levels due to cysteine deficiency.
Cysteine-dependent glutathione deficiency
A man presents with urine smelling like rotten eggs.
High sulfur amino acid metabolism → benign sulfur excretion
(seen after high garlic/onion diet)
A. Alanine
B. Serine
C. Glycine
D. Threonine
Answer: C
A. B6
B. B12
C. Folate
D. Pyridoxal phosphate
Answer: D
A. Cystathioninuria
B. Homocystinuria
C. Cystinuria
D. Tyrosinemia
Answer: C
A. Serine
B. Alanine
C. Glycine
D. Ornithine
Answer: B
A. Liver ↔ Kidney
B. Muscle ↔ Liver
C. Intestine ↔ Muscle
D. Brain ↔ Blood
Answer: B
A. Glycine transaminase
B. Alanine–glyoxylate aminotransferase
C. DOPA oxidase
D. Glyoxylase
Answer: B
A. Enzyme product
B. Spontaneous breakdown product of creatine phosphate
C. Hormone
D. RNA precursor
Answer: B
A. Enzyme inhibitor
B. Energy buffer
C. Neurotransmitter
D. Lipid precursor
Answer: B
A. B1
B. B2
C. PLP + THF
D. Biotin
Answer: C
A. AUG
B. UAA
C. UGA
D. UAG
Answer: C
UGA normally stops, but becomes Sec in presence of SECIS element.
A. THF
B. SAM
C. SAH
D. Methyl-B12
Answer: B
A. B6 only
B. B2 + folate
C. B12 + folate
D. Vitamin C
Answer: C
A. Thrombosis
B. Downward lens dislocation
C. High homocysteine
D. High cysteine
Answer: D
(Cysteine ↓ because transsulfuration is blocked)
A. CBS deficiency
B. B12 deficiency
C. MTHFR deficiency
D. Vitamin C deficiency
Answer: C
A. Homocystinuria
B. Cystathioninuria
C. MSUD
D. Tyrosinemia
Answer: B
A. Methionine
B. Cysteine
C. Threonine
D. Alanine
Answer: B
A. Glycine
B. Glutamate
C. Cysteine
D. Serine
Answer: C
A. Glu–Ala–Gly
B. Gly–Met–Ser
C. Glu–Cys–Gly
D. Ala–Cys–Gly
Answer: C
A. Tyrosine
B. Selenocysteine
C. Hydroxyproline
D. Homocysteine
Answer: B
A. Homocysteine
B. Cystathionine
C. Thiosulfate
D. Inorganic sulfate
Answer: D
A. Methionine synthase
B. MTHFR
C. Cystathionine β-synthase
D. Cystathionine γ-lyase
Answer: C
A. SAM lyase
B. Methionine adenosyltransferase
C. Methionine reductase
D. SAM synthase
Answer: B
A. Alanine
B. Glycine
C. Serine
D. Cysteine
Answer: D
A. Urea cycle
B. One-carbon pool (via betaine)
C. Ketogenesis
D. Pyruvate metabolism
Answer: B
A. Catalase
B. Peroxidase
C. Glutathione
D. Uric acid
Answer: C
A. Glycine
B. Cysteine
C. Serine
D. Alanine
Answer: B
A. Homocystinuria
B. Cystinuria
C. MSUD
D. Phenylketonuria
Answer: B
A. NAD
B. FAD
C. Coenzyme A
D. ATP
Answer: C
A. Riboswitch
B. SECIS element
C. Telomerase
D. Thiamine
Answer: B
A. Liver function
B. Glomerular filtration rate (GFR)
C. Thyroid function
D. Lipid oxidation
Answer: B
Glycine.
No, it is the only amino acid without one.
Glycine + succinyl-CoA → δ-ALA, first step of heme synthesis.
Glycine.
Non-ketotic hyperglycinemia.
Arginine + glycine, later methylated by SAM.
Spontaneous breakdown product of creatine phosphate, marker of GFR.
Genetic defect in alanine–glyoxylate aminotransferase, causing excess oxalate.
Hexagonal crystals.
Cystine, Ornithine, Lysine, Arginine (COLA).
Alanine.
Glucose–alanine cycle.
3-phosphoglycerate.
PLP (B6) and THF.
Generation of one-carbon units for nucleotide synthesis.
Yes, threonine is an essential amino acid.
Cysteine.
Because it depends on methionine for synthesis.
SAM (S-adenosylmethionine).
Cystathionine β-synthase (CBS), B6-dependent.
Homocysteine ↑↑ and methionine ↑.
Downward.
Type II and Type III (remethylation defects — methionine synthase or MTHFR).
Deficiency of cystathionine γ-lyase, usually benign.
Selenocysteine.
SECIS element.
Glutathione peroxidase.
Tripeptide: Glu–Cys–Gly.
Glutathione reductase, using NADPH.
Glutathione (GSH).
Inorganic sulfate.
Vitamin B6.
Methionine adenosyltransferase.
Cysteine.
Norepinephrine → Epinephrine.
Because methionine synthase cannot remethylate homocysteine.
Defective connective tissue → weak collagen cross-linking.
Cyanide–nitroprusside test.
Coenzyme A.
Mucins (O-linked glycoproteins).
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