Salih J. Wakil, Ph.D.
Distinguished Service Professor
Lodwick T. Bolin Professor, Biochemistry & Molecular Biology
Baylor College of Medicine
B.Sc. Chemistry, American University of Beirut (1948)
Ph.D. Biochemistry, University of Washington at Seattle (1952)
Research is centered around the biosynthesis of fatty acids and its regulation. Two unusually large multifunctional enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), are involved in the synthesis of palmitic acid from acetyl-CoA. Current studies in Dr. Wakil's laboratory concern the human enzymes.
Human ACC is present in two isoforms. The cDNAs of both isoforms have been cloned and sequenced and will be expressed in an appropriate expression system in order to study the structure-function relationships of the isoforms. ACC is highly regulated by both allosteric and covalent modifications, many of which are controlled by hormones such as insulin, glucagon, epinephrine, and growth hormones. The 5´-flanking sequences of the two ACC isoforms will be cloned, and using appropriate reporter gene constructs, the effects of these hormones on the expression of the ACC gene will be studied.
The human FAS is another remarkable multifunctional enzyme. The human FAS cDNA has been expressed, and large enough quantities of the active enzyme have been obtained to study its structure-function. Two promoters that regulate FAS expression were identified by utilizing constructs of the 5´-flanking region with luciferase as a reporter gene. The activities of the two promoters and their interaction are under investigation.
- Abu-Elheiga L, Wu H, Gu Z, Bressler R and Wakil SJ. Acetyl-CoA carboxylase 2-/- mutant mice are protected against fatty liver under high-fat, high-carbohydrate dietary and de novo lipgenic conditions. J Biol Chem, 287(15):12578-88 (2012). PubMed
- Zhang W, Chakravarty B, Zheng F, Gu Z, Wu H, Mao J, Wakil SJ and Quiocho FA. Crystal structure of FAS thioesterase domain with polyunsaturated fatty acyl adduct and inhibition by dihomo-gamma-linolenic acid. Proc Natl Acad Sci USA, 108(38):15757-62 (2011). PubMed
- Dong B, Saha PK, Huang W, Chen W, Abu-Elheiga LA, Wakil SJ, Stevens RD, Ilkayeva O, Newgard CB, Chan L and Moore DD. Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease. Proc Natl Acad Sci USA, 106(44):18831-6 (2009). PubMed
- Wakil SJ and Abu-Elheiga LA. Fatty acid metabolism: target for metabolic syndrome. J Lipid Res, 50 Suppl:S138-43 (2009). PubMed
- Mao J, DeMayo FJ, Li H, Abu-Elheiga L, Gu Z, Shaikenov TE, Kordari P, Chirala SS, Heird WC and Wakil SJ. Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis. Proc Natl Acad Sci USA 103(22):8552-7, (2006). PubMed
- Abu-Elheiga L, Matzuk MM, Kordari P, Oh W, Shaikenov T, Gu Z, Wakil SJ. Mutant mice lacking acetyl-CoA caroxylase 1 are embryonically lethal. Proc Natl Acad Sci USA, 102(34):12011-6 (2005). PubMed
- Chirala SS and Wakil SJ. Structure and function of animal fatty acid synthase. Lipids, 39(11):1045-53 (2004) PubMed
For more publications, see listing on PubMed.
Address: Baylor College of Medicine
One Baylor Plaza
Houston, Texas 77030
Additional Links: Biochemistry and Molecular Biology