Pathways & interactions
Fumarylacetoacetase, C-terminal-related (IPR011234)
Short name: Fumarylacetoacetase_C-rel
Fumarylacetoacetase (EC:184.108.40.206; also known as fumarylacetoacetate hydrolase or FAH) catalyses the hydrolytic cleavage of a carbon-carbon bond in fumarylacetoacetate to yield fumarate and acetoacetate as the final step in phenylalanine and tyrosine degradation [PMID: 11154690]. This is an essential metabolic function in humans, the lack of FAH causing type I tyrosinaemia, which is associated with liver and kidney abnormalities and neurological disorders [PMID: 9101289, PMID: 16602095]. The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole [PMID: 10508789]. FAH folds into two domains: an N-terminal domain SH3-like beta-barrel, and a C-terminal with an unusual fold consisting of three layers of beta-sheet structures [PMID: 10508789].
This entry represents the C-terminal domain of fumarylacetoacetase, as well as other domains that share a homologous alpha/beta structure, including:
- 5-carboxymethyl-2-hydroxymuconate delta-isomerase (CHM isomerase; EC:220.127.116.11), which catalyses the conversion of 5-carboxymethyl-2-hydroxymuconate to 5-carboxy-2-oxohept-3-enedioate [PMID: 2194841].
- 5-oxopent-3-ene-1,2,5-tricarboxylate decarboxylase (OPET decarboxylase; EC:18.104.22.168), which catalyses the conversion of 5-oxopent-3-ene-1,2,5-tricarboxylate to 2-oxohept-3-enedioate and carbon dioxide.
- Bifunctional enzyme HpcE (OPET decarboxylase EC:22.214.171.124/HHDD isomerase EC:126.96.36.199), which is a duplication consisting of a tandem repeat of two FAH C-terminal-like domains. This enzyme is responsible for the degradation of 4-hydroxyphenylacetate, a product of tyrosine and phenylalanine metabolism also released by lignin catabolism [PMID: 11863436].
- 2-keto-4-pentenoate hydratase MhpD (EC:188.8.131.52; also known as 2-oxopent-4-enoate hydratase), which converts 4-hydroxy-2-oxopentanoate to 2-oxopent-4-enoate [PMID: 10537203].
- 4-oxalocrotonate decarboxylase (4-OD; EC:184.108.40.206), which catalyses the conversion of 4-oxalocrotonate to 2-oxopent-4-enoate and carbon dioxide [PMID: 10651637].
- 2-oxo-hepta-3-ene-1,7-dioic acid hydratase, which hydrates the double bond of 2-oxo-hepta-3-ene-1,7-dioic acid to form 4-hydroxy-2-oxo-heptane-1,7-dioic acid in the catabolism of 4-hydroxyphenylacetic acid.