Thiolases are ubiquitous enzymes that have key roles in many vital biochemical pathways, including the beta oxidation pathway of fatty acid degradation and various biosynthetic pathways.[1] Members of the thiolase family can be divided into two broad categories: degradative thiolases (EC 2.3.1.16) and biosynthetic thiolases (EC 2.3.1.9). These two different types of thiolase are found both in eukaryotes and in prokaryotes: acetoacetyl-CoA thiolase (EC:2.3.1.9) and 3-ketoacyl-CoA thiolase (EC:2.3.1.16). 3-ketoacyl-CoA thiolase (also called thiolase I) has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase (also called thiolase II) is specific for the thiolysis of acetoacetyl-CoA and involved in biosynthetic pathways such as beta-hydroxybutyric acid synthesis or steroid biogenesis.
The formation of a carbon–carbon bond is a key step in the biosynthetic pathways by which fatty acids and polyketide are made. The thiolase superfamily enzymes catalyse the carbon–carbon-bond formation via a thioester-dependent Claisen condensation[2] reaction mechanism.[3]
^Thompson S, Mayerl F, Peoples OP, Masamune S, Sinskey AJ, Walsh CT (July 1989). "Mechanistic studies on beta-ketoacyl thiolase from Zoogloea ramigera: identification of the active-site nucleophile as Cys89, its mutation to Ser89, and kinetic and thermodynamic characterization of wild-type and mutant enzymes". Biochemistry. 28 (14): 5735–42. doi:10.1021/bi00440a006. PMID2775734.
^Heath RJ, Rock CO (October 2002). "The Claisen condensation in biology". Nat Prod Rep. 19 (5): 581–96. doi:10.1039/b110221b. PMID12430724.
^Haapalainen AM, Meriläinen G, Wierenga RK (January 2006). "The thiolase superfamily: condensing enzymes with diverse reaction specificities". Trends Biochem. Sci. 31 (1): 64–71. doi:10.1016/j.tibs.2005.11.011. PMID16356722.
