Homogentisate catabolism

The module begins at homogentisate so that phenylalanine, tyrosine, 3-hydroxyphenylacetate, and other upstream routes can connect without being treated as required parts; 4-hydroxyphenylpyruvate dioxygenase (HPD) is the upstream step in aromatic amino acid catabolism and is outside this boundary. The biology is pan-domain, so the module is abstract: P. putida KT2440 hmgA/hmgC/hmgB (a contiguous hmgABC cluster), the experimentally characterized Aspergillus nidulans hmgA/maiA/fahA cluster (which also seeds the three PAINT nodes), and the human HGD/GSTZ1/FAH disease enzymes are the representative members, one bacterial, one fungal and one animal exemplar per step. The KT2440 members receive the corresponding terms by TreeGrafter IEA from PANTHER nodes PTN002252947, PTN002448156 and PTN002453800 rather than through these IBD nodes, so the ancestral nodes are cited as family-level evidence, not as the source of the bacterial annotations. Within PTHR42673 the bacterial MaiA/HmgC proteins fall in subfamily SF21, together with E. coli YfcF and the gentisate-pathway maleylpyruvate isomerase NagL, so membership of the family alone does not establish maleylacetoacetate isomerase activity; pathway context (gene clustering with hmgA/hmgB) does. In plants the homogentisate pool is also the precursor of tocopherols and plastoquinones; that biosynthetic use is outside this catabolic module. A nonenzymatic glutathione-mediated maleylacetoacetate isomerization bypass has been reported in MAAI-deficient mammalian contexts; it is not modeled here as a general enzymatic variant because the zeta-class isomerase is the canonical implementation of this step.

Connections