Fumarylacetoacetate

Fumarylacetoacetate (FAA) is a key compound in the metabolic pathway known as the tyrosine catabolic pathway. This pathway is responsible for the breakdown and disposal of excess tyrosine, an amino acid that is used in the synthesis of proteins.

Structure and Properties

Fumarylacetoacetate is a dicarboxylic acid that is the diester of fumaric acid and acetoacetic acid. It has a molecular formula of C8H6O6 and a molecular weight of 198.13 g/mol. The structure of fumarylacetoacetate consists of a fumarate moiety and an acetoacetate moiety, linked by an ester bond.

Role in Metabolism

In the tyrosine catabolic pathway, fumarylacetoacetate is produced from the enzymatic action of 4-hydroxyphenylpyruvate dioxygenase on homogentisate. This reaction is followed by the conversion of fumarylacetoacetate to fumarate and acetoacetate by the enzyme fumarylacetoacetate hydrolase (FAH).

Fumarate can then enter the citric acid cycle, also known as the Krebs cycle, where it is converted to malate and then to oxaloacetate, contributing to the production of adenosine triphosphate (ATP), the main energy currency of the cell. Acetoacetate, on the other hand, can be used in the synthesis of ketone bodies, which serve as an alternative energy source during periods of fasting or intense exercise.

Clinical Significance

Mutations in the FAH gene, which codes for the enzyme that breaks down fumarylacetoacetate, can lead to a rare genetic disorder known as hereditary tyrosinemia type 1 (HT1). In individuals with HT1, fumarylacetoacetate accumulates in the body, leading to liver and kidney damage, neurological problems, and a heightened risk of liver cancer.

Treatment for HT1 typically involves a diet low in tyrosine and phenylalanine (another amino acid that can be converted to tyrosine), as well as the use of a drug called nitisinone, which inhibits the production of fumarylacetoacetate.

File:Fumarylacetoacetate.png

Chemical structure of fumarylacetoacetate.

See Also

• Tyrosine metabolism
• Hereditary tyrosinemia type 1
• Fumarylacetoacetate hydrolase