Thioesterase

Thioesterase is a type of enzyme that catalyzes the hydrolysis of thioester bonds. Thioester bonds are commonly found in many biological systems, including in the synthesis of fatty acids and polyketides. Thioesterases play a crucial role in these processes by terminating the elongation cycle of the fatty acid or polyketide chain.

Structure and Function

Thioesterases are typically composed of a single polypeptide chain, with a catalytic triad consisting of a serine, a histidine, and an aspartic acid or glutamic acid. The serine acts as a nucleophile, attacking the carbonyl carbon of the thioester bond, while the histidine and aspartic acid or glutamic acid act as a base, deprotonating the serine and stabilizing the transition state.

Thioesterases are involved in a wide range of biological processes. In addition to their role in fatty acid and polyketide synthesis, they are also involved in the degradation of coenzyme A (CoA) esters, the regulation of signal transduction pathways, and the post-translational modification of proteins.

Types of Thioesterases

There are two main types of thioesterases: type I and type II. Type I thioesterases are involved in the termination of fatty acid synthesis, while type II thioesterases are involved in the termination of polyketide synthesis. Both types of thioesterases are found in a wide range of organisms, from bacteria to humans.

Clinical Significance

Mutations in the genes encoding thioesterases can lead to a variety of diseases. For example, mutations in the gene encoding the thioesterase ACOT1 have been associated with neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Additionally, overexpression of the thioesterase FASN has been linked to cancer, as it is involved in the synthesis of fatty acids, which are essential for cell growth and proliferation.

File:Thioesterase.png

Structure of a thioesterase enzyme.

See Also

• Enzyme
• Thioester
• Fatty acid synthesis
• Polyketide synthesis
• Coenzyme A
• Signal transduction
• Post-translational modification