Category: catabolism
Beyond catecholamine biosynthesis (see catecholamine_synthesis pathway), tyrosine has a major degradation route through the homogentisic acid (HGA) pathway. Tyrosine → 4-hydroxyphenylpyruvate (TAT) → HGA (HPPD — 4-hydroxyphenylpyruvate dioxygenase) → maleylacetoacetate → fumarylacetoacetate → fumarate + acetoacetate. Enzyme defects: hereditary tyrosinemia type 1 (FAH deficiency — toxic fumarylacetoacetate accumulates; NITISINONE rescues by blocking HPPD upstream); alkaptonuria (HGD deficiency — HGA accumulates, oxidizes to alkapton causing ochronosis + arthritis; nitisinone is also being investigated here). HPPD is the same enzyme inhibited by mesotrione + nitisinone — the latter repurposed from herbicide development for tyrosinemia.