STEPTRACKERBIOCHEMISTRY + PHARMACOLOGY + NEUROLOGY | AMINO ACID METABOLISM | HIGH-YIELD REVIEW

Amino Acid Derivatives

Amino acids are building blocks for hormones, neurotransmitters, heme and signaling molecules — know each parent and its products.

FOCUS ON
Phenylalanine → tyrosine → DOPA → dopamine → NE → epinephrine (also thyroxine, melanin). Tryptophan → serotonin → melatonin; also → niacin (needs B6). Histidine → histamine. Glycine → heme (porphyrin), creatine. Arginine → NO, creatine, urea. Glutamate → GABA (B6), glutathione. Essential amino acids: Phe, Val, Thr, Trp, Ile, Met, His, Leu, Lys.
PARENT
PRODUCTS
KEY ENZYMES · COFACTORS
CLUE
Phenylalanine → tyrosine
Tyrosine (becomes conditionally essential in PKU)
Phenylalanine hydroxylase · BH4
Defect = PKU (9.03)
Tyrosine
DOPA → dopamine → norepinephrine → epinephrine · thyroxine · melanin
Tyrosine hydroxylase (BH4, rate-limiting) · DOPA decarboxylase (B6) · dopamine β-hydroxylase (vitamin C, Cu) · PNMT (SAM; induced by cortisol)
Metyrosine blocks tyrosine hydroxylase (pheochromocytoma) · carbidopa blocks peripheral DOPA decarboxylase
Catecholamine breakdown
Dopamine → HVA · NE → normetanephrine, VMA · epinephrine → metanephrine, VMA
MAO, COMT
↑ Metanephrines = pheochromocytoma · ↑ HVA/VMA = neuroblastoma
Tryptophan
Serotonin (5-HT) → melatonin · niacin (NAD⁺)
Tryptophan hydroxylase (BH4) · decarboxylase (B6)
Carcinoid diverts Trp → serotonin → pellagra; 5-HIAA in urine
Histidine
Histamine
Histidine decarboxylase (B6)
Mast cells, ECL cells
Glycine
Porphyrins (heme) with succinyl-CoA · creatine · glutathione · bile acid conjugates
ALA synthase (B6)
Inhibitory neurotransmitter in spinal cord (tetanus/strychnine)
Arginine
Nitric oxide (+ citrulline) · creatine · urea · polyamines
NO synthase (NADPH, BH4)
Conditionally essential in growth
Glutamate
GABA · glutathione · glutamine
Glutamate decarboxylase (B6)
Anti-GAD antibodies: type 1 diabetes, stiff-person syndrome
Methionine
S-adenosylmethionine (SAM — universal methyl donor) → homocysteine → cysteine
B12, folate, B6 for homocysteine handling
SAM needed for NE → epinephrine and DNA methylation
Ketogenic vs glucogenic
Purely ketogenic: leucine, lysine · both: Phe, Tyr, Trp, Ile, Thr · rest glucogenic
—
Acidic: Asp, Glu · basic: Arg (most basic), Lys, His (uncharged at body pH)

Mechanism — catecholamine synthesis

Phenylalanine
→
TyrosinePAH (BH4)
→
DOPATyrosine hydroxylase (BH4) — rate-limiting
→
DopamineDecarboxylase (B6)
→
NorepinephrineDβH (vit C, Cu)
→
EpinephrinePNMT (SAM, cortisol)

PNMT is induced by cortisol from the cortex that drains through the medulla — why epinephrine comes from the adrenal medulla.

Breakdown products as tumor markers

MARKER
FROM
TUMOR
Metanephrines
Epinephrine, NE
Pheochromocytoma
VMA, HVA
NE / dopamine
Neuroblastoma
5-HIAA
Serotonin
Carcinoid syndrome

How it's tested

COMMON CONFUSIONBH4 is needed by phenylalanine, tyrosine and tryptophan hydroxylases — BH4 deficiency lowers dopamine and serotonin too, unlike classic PKU.
THE TRAPCarcinoid patients can develop pellagra: tryptophan is diverted to serotonin, leaving too little for niacin.
YOUR APPROACHName the product → trace back to the parent amino acid → enzyme and cofactor → drug or deficiency that blocks it.

If you see… think…

Rate-limiting enzyme of catecholamine synthesis → tyrosine hydroxylase
Cofactor for DOPA decarboxylase → B6
Cofactors of dopamine β-hydroxylase → vitamin C, copper
Hormone inducing PNMT → cortisol
Precursor of melatonin → serotonin (tryptophan)
Precursor of nitric oxide → arginine
Precursor of GABA → glutamate
Amino acid combining with succinyl-CoA for heme → glycine
Purely ketogenic amino acids → leucine, lysine
↑ Urine 5-HIAA → carcinoid syndrome