Thiolase - Biological Function

Biological Function

In eukaryotic cells, especially in mammalian cells, thiolases exhibit diversity in intracellular localization related to their metabolic functions as well as in substrate specificity. For example, they contribute to fatty-acid β-oxidation in peroxisomes and mitochondria, ketone body metabolism in mitochondria, and the early steps of mevalonate pathway in peroxisomes and cytoplasm. In addition to biochemical investigations, analyses of genetic disorders have made clear the basis of their functions. Genetic studies have also started to disclose the physiological functions of thiolases in the yeast Saccharomyces cerevisiae. Thiolase is of central importance in key enzymatic pathways such as fatty-acid, steroid and polyketide synthesis. The detailed understanding of its structural biology is of great medical relevance, for example, for a better understanding of the diseases caused by genetic deficiencies of these enzymes and for the development of new antibiotics. Harnessing the complicated catalytic versatility of the polyketide synthases for the synthesis of biologically and medically relevant natural products is also an important future perspective of the studies of the enzymes of this superfamily.