Amino Acid Derivatives & Inborn Errors of Metabolism

Ten vocabulary flashcards covering key amino-acid-derived molecules and related metabolic disorders.

Phenylketonuria (PKU)

An inborn error caused by defective phenylalanine hydroxylase or tetrahydrobiopterin metabolism, blocking conversion of phenylalanine to tyrosine, and instead converting Phenylalanine into phenylpyruvate, then phenyllactate + phenylacetate. This causes an accumulation of phenylalanine and a lack of tyrosine, which can be identified from a paper blood spot.

Maple Syrup Urine Disease (MSUD)

Genetic deficiency of the branched-chain α-keto acid dehydrogenase complex (BCKDC), leading to toxic accumulation of leucine, isoleucine, valine and their keto acids (KIC, KMV, KIV). The high concentration of leucine in the brain competes with its ability to uptake Phe, Glu, His, Met, and Try, harming brain growth, neurotransmitter production, and myelin synthesis.

Homocystinuria

Disorder resulting from impaired conversion of homocysteine to methionine or cysteine (e.g., cystathionine β-synthase defect), leading to a build-up of homocysteine

Glutathione

Tripeptide antioxidant composed of glutamate, cysteine, and glycine; cysteine supply depends on homocysteine transsulfuration.

Normal phenylalanine to tyrosine pathway (phenylketonuria)

Phenylalanine + BH4 (tetrahydrobiopterin) → (via phenylalanine hydroxylase) Tyrosine + qBH2

Tyrosine derivatives

Tyrosine → (via tyrosine hydroxylase + BH4) L-DOPA → melanin, (via aromatic AA decarboxylase) Dopamine → (via domaine B-hydroxylase + ascorbate) Norepinephrine → (via phenyethanolamine N-methyltransferase) Epinephrine

Normal BCKDC pathway (MSUD)

Leu, Iso, Val → KIC, KMV, KIV → BCKDC → Isovaleryl-CoA → acetyl-CoA + acetoacetate; a-Methylbutyryl-CoA → acetyl-CoA + succinyl-CoA; Isobutyryl-CoA → succinyl-CoA

Tryptophan derivatives

Tryptophan → (via tryptophan hydroxylase) 5-hydroxytryptophan → (via aromatic L-AA decarboxylase) Serotonin → (via serotonin N-acetyltransferase) N-acetylserotonin → (via acetylserotonin O-methyltransferase) Melatonin

Methionine to cysteine normal pathway (homocystinuria)

Methionine → S-adenosylmethinonine (SAM) → Homocysteine → (via cystathionine B-synthase + PLP) Cystathionine → Cysteine. Homocystein can also go back to methionine via methionine synthase and folic acid (B9) and cobalamin (B12).