GLUCOSE FATTY-ACID INTERACTIONS AND THE REGULATION OF GLUCOSE DISPOSAL

Glucose is essential for the energy metabolism of some cells and conse rvation of glucose is obligatory for survival during starvation. The p rincipal site of this glucose conservation is the mitochondrial pyruva te dehydrogenase (PDH) complex, which is regulated by reversible phosp horylation (phosphorylation is inactivating). In cells in which glucos e oxidation is switched off during starvation, fatty acids are used as fuel, and acetyl CoA and NADH formed by beta-oxidation promote phosph orylation of PDH complex by activation of PDH kinase. A longer-term me chanism further increases PDH kinase activity in response to cAMP and products of beta-oxidation of fatty acids. Coordinated inhibition of g lycolytic flux mediated by effects of citrate on PFK1 and PFK2 in musc les and liver results in an associated inhibition of glucose uptake. S imilar mechanisms lead to impaired glucose oxidation in diabetes. (C) 1994 Wiley-Liss, Inc.