Phenylalanine metabolism

Category: catabolism

Overview

Phenylalanine → tyrosine via PHENYLALANINE HYDROXYLASE (PAH, BH4-dependent). PAH deficiency = phenylketonuria (PKU), the prototype inborn error of metabolism. Phenylalanine accumulates and is metabolized via alternative deamination → phenylpyruvate + phenylacetate + phenyllactate, which are excreted in urine (the "musty" odor). Untreated PKU → severe intellectual disability + microcephaly + seizures due to phenylalanine neurotoxicity (mechanism: competes with other large neutral amino acids for LAT1 BBB transport, depleting brain serotonin + catecholamine precursors). Treatment: phenylalanine-restricted diet from birth (newborn screening detects). SAPROPTERIN = synthetic BH4 cofactor; rescues partial-deficiency PAH variants. PEGVALIASE = recombinant phenylalanine ammonia lyase enzyme replacement (Palynziq, 2018).

Organ Systems

Pathway Steps

  1. phenylalanine → tyrosine — via phenylalanine hydroxylase (PAH) — BH4 cofactor; PKU deficiency enzyme. Phenylalanine hydroxylase (BH4-dependent) converts phenylalanine to tyrosine; its deficiency causes phenylketonuria (PKU), where accumulating phenylalanine is neurotoxic — managed by lifelong Phe restriction (and sapropterin in BH4-responsive forms). BH4-cofactor defects cause atypical PKU that also impairs monoamine synthesis.

Known Modulators

References