City College of CUNY
Department of Chemistry
Biochemistry Seminar
Wednesday, February 23, 2000
Room J1027
11:15 AM
Professor Kho Kashfi
Sophie Davis School for Biomedical=20 Education
CUNY Medical School
Department of Pharmacology and Director of Chemistry
Regulation of Hepatic Mitochondrial Carnitine-Palmitoyl Transferases
ABSTRACT

Abstract: Carnitine palmitoyltransferase (CPT; EC 2.3.1.21) is generally recognized as the most important regulatory enzyme in the hepatic mitochondrial fatty acid oxidation pathway. CPT activities are expressed in rat liver mitochondria both inside and outside the mitochondrial inner membrane barrier to the diffusion of coenzyme A derivatives of fatty acids. The inner carnitine palmitoyltransferase (CPT-II) resides on the inner aspect of the mitochondrial inner membrane and the overt mitochondrial carnitine palmitoyltransferase (CPT-I) is located in the mitochondrial outer membrane. CPT-I has at least two different binding domains, one that binds acyl-CoA and another that binds malonyl-CoA. Multiple mechanisms are involved in the regulation of the CPTs and fatty acid oxidation. CPT-I is regulated by malonyl-CoA, its physiological inhibitor, and its activity and sensitivity to inhibition by malonyl-CoA are altered by changes in physiological and pathophysiological conditions. Quantitatively, the most significant change that occurs with the onset of diabetes or feeding-starvation transition is at least a 10-fold increase in the apparent Ki for malonyl-CoA. Insulin-dependent diabetes increase mRNA levels for CPT-I and insulin treatment decreases CPT-I mRNA and increases malonyl-CoA sensitivity primarily by decreasing gene transcription. Recent data suggests that these insulin effects are independent of cAMP. Also, recent experiments have examined specific effects of phospholipids on CPT-I in isolated mitochondrial outer membranes and on CPT-II after expression in E. coli. The results indicate that there is a common phospholipid activation of all four proteins involved in the activation and transfer of fatty acids into rat liver mitochondria. A model is presented to suggest possible interactions of these proteins with each other and with the mitochondrial membranes.

Coffee and Tea	Lecture begins promptly
11:15 AM	11:25 AM