The Role of Pyruvate Dehydrogenase Kinase in Diabetes and Obesity

ABSTRACT

The pyruvate dehydrogenase complex (PDC) is an emerging target for the treatment of metabolic syndrome. To maintain a steady-state concentration of adenosine triphosphate during the feed-fast cycle, cells require efficient utilization of fatty acid and glucose, which is controlled by the PDC. The PDC converts pyruvate, coenzyme A (CoA), and oxidized nicotinamide adenine dinucleotide (NAD+) into acetyl-CoA, reduced form of nicotinamide adenine dinucleotide (NADH), and carbon dioxide. The activity of the PDC is up- and down-regulated by pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase, respectively. In addition, pyruvate is a key intermediate of glucose oxidation and an important precursor for the synthesis of glucose, glycerol, fatty acids, and nonessential amino acids.