Fumarylacetoacetase

Fumarylacetoacetase, also known as FAH, is an enzyme that plays a crucial role in the breakdown of tyrosine, an amino acid. Specifically, it is the final enzyme in the tyrosine catabolism pathway. This enzyme catalyzes the hydrolysis of fumarylacetoacetate into fumarate and acetoacetate. Fumarate is an intermediate in the citric acid cycle, and acetoacetate is a ketone body.

The gene encoding human fumarylacetoacetase is located on chromosome 11. Mutations in this gene are responsible for tyrosinemia type I, a rare autosomal recessive metabolic disorder. In tyrosinemia type I, the deficiency in functional FAH leads to the accumulation of fumarylacetoacetate and its toxic metabolites, such as maleylacetoacetate and succinylacetone. These accumulated substances cause severe damage to the liver and kidneys.

Symptoms of tyrosinemia type I can include vomiting, diarrhea, failure to thrive, jaundice, and liver dysfunction. Without treatment, the condition can lead to cirrhosis and liver cancer. Treatment typically involves a low-tyrosine diet and medication to inhibit the enzyme 4-hydroxyphenylpyruvate dioxygenase, which is upstream of the FAH enzyme. Liver transplantation is also a curative option for severe cases.