maleylacetoacetate

Maleylacetoacetate is a biochemical intermediate in the catabolism of the amino acids phenylalanine and tyrosine. It is formed in the tyrosine degradation pathway from p-hydroxyphenylpyruvate by the action of p-hydroxyphenylpyruvate dioxygenase and is subsequently converted to fumarylacetoacetate by maleylacetoacetate isomerase.

The enzyme maleylacetoacetate isomerase, also known as GSTZ1, is a member of the glutathione S-transferase family. It catalyzes the isomerization of maleylacetoacetate to fumarylacetoacetate, which is then hydrolyzed by fumarylacetoacetase (FAH) to yield fumarate and acetoacetate. These products feed into central metabolic pathways such as the citric acid cycle. In humans, GSTZ1/MAAI participates both in this tyrosine catabolic step and in glutathione-dependent detoxification reactions, reflecting a dual role in metabolism and xenobiotic processing.

The tyrosine degradation pathway links amino acid catabolism to energy metabolism, and maleylacetoacetate represents a transient intermediate within this network. Genetic variation or regulation of the enzymes involved can influence metabolite levels and drug metabolism. Clinically, disorders of the pathway are most prominently associated with fumarylacetoacetate accumulation in fumarylacetoacetase deficiency (tyrosinemia type I), rather than with maleylacetoacetate itself. In research and clinical biochemistry, maleylacetoacetate is mainly discussed as a step in understanding tyrosine metabolism and the function of GSTZ1.