Maleylacetoacetate isomerase

4-Maleylacetoacetate isomerase belongs to the zeta class of the glutathione S-transferase (GST) superfamily.

[1] In the  phenylalanine degradation pathway, 4-maleylacetoacetate isomerase catalyzes a cis-trans isomerization of  4-maleylacetoacetate to fumarylacetoacetate.

[1] Ser 15, Cys 16, Gln 111, and the helix dipole of alpha 1 of the enzyme stabilize the thiolate form of glutathione which activates it to attack the alpha carbon of 4-maleylacetoacetate, thus breaking the double bond and allowing rotation around the single bond.

[2] The conversion of 4-maleylacetoacetate to fumarylacetoacetate is a step in the catabolism of phenylalanine and tyrosine, amino acids acquired through dietary protein consumption.

When 4-maleylacetoacetate isomerase is unable to function properly, the 4-maleylacetoacetate may be converted instead to succinylacetoacetate and further broken down into succinate and acetoacetate by fumarylacetoacetate hydrolase.

Mutations in 4-maleylacetoacetate isomerase resulted in accumulation of fumarylacetoacetate and succinylacetone in the urine, but individuals were otherwise healthy.

This image shows the structure of the peptide backbone of 4-maleylacetoacetate isomerase, highlighting the glutathione binding site.
This image shows the conversion of 4-maleylacetoacetate to fumarate and acetoacetate, as well as the enzymes that catalyze each step and cofactors required.
This image shows the pathway that 4-maleylacetoacetate follows when 4-maleylacetoacetate isomerase is not present.
This image shows the folding patterns, as well as both the N- and C-terminals of the enzyme 4-maleylacetoacetate isomerase.
This graph shows where the gene that encodes 4-maleylacetoactetate isomerase is most highly expressed.