Fumarylacetoacetase

Fumarylacetoacetase (also known as FAH) is an enzyme that plays a crucial role in the metabolism of amino acids, specifically the breakdown of tyrosine. It is the last enzyme in the tyrosine catabolic pathway, catalyzing the hydrolysis of 4-fumarylacetoacetate to fumarate and acetoacetate.

Structure

The FAH gene, located on chromosome 15, encodes the fumarylacetoacetase enzyme. The enzyme is a homodimer, meaning it consists of two identical subunits. Each subunit is composed of approximately 400 amino acids.

Function

Fumarylacetoacetase catalyzes the final step in the tyrosine degradation pathway. This process involves the conversion of 4-fumarylacetoacetate into two simpler substances: fumarate and acetoacetate. Fumarate can then enter the citric acid cycle, also known as the Krebs cycle, to be converted into energy. Acetoacetate is one of the ketone bodies, which can be used as an energy source by the brain and heart when glucose levels are low.

Clinical significance

Mutations in the FAH gene can lead to a condition known as tyrosinemia type I. This is a severe metabolic disorder characterized by elevated blood levels of tyrosine and its metabolites, leading to liver and kidney damage, neurological problems, and an increased risk of liver cancer. Treatment typically involves a low-protein diet and medication to reduce tyrosine levels.

See also

• Tyrosine metabolism
• Tyrosinemia
• Enzyme