Category: catabolism
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).