Inhibition of Glucose 6-Phosphate Dehydrogenase by Palmitoyl Coenzyme A

Abstract

Abstract Low concentrations of palmitoyl coenzyme A inhibit yeast glucose-6-P dehydrogenase (Taketa, K., and Pogell, B. M. (1966) J. Biol. Chem. 241, 720). This inhibition is prevented or reversed by bovine serum albumin, mycobacterial polysaccharides, or alkylated cyclodextrins. Sephadex chromatography and sucrose density gradient centrifugation show that palmitoyl-CoA inhibits by dissociating the tetrameric dehydrogenase to dimeric, enzymatically inactive subunits. These structural changes are accompanied by firm binding of palmitoyl-CoA to the dimeric subunit and by release of NADP. After removal of the (nondialyzable) inhibitor from the palmitoyl-CoA-dimer complex by alkylated cyclodextrin the subunits reaggregate to enzymatically active tetramer. Reaggregation does not require NADP. In contrast to palmitoyl-CoA, sodium dodecyl sulfate dissociates yeast dehydrogenase to monomers. It is concluded that palmitoyl-CoA, unlike the synthetic anionic detergent, perturbs the dehydrogenase subunit structure in a controlled manner which may be important for regulating the activity of lipogenic enzymes. The dimeric glucose-6-P dehydrogenase from Leuconostoc mesenteroides is inhibited only by high concentrations of palmitoyl-CoA. In this instance palmitoyl-CoA neither binds to the enzyme nor dissociates it. Torulopsis utilis glucose-6-P dehydrogenase, also dimeric, is irreversibly converted to inactive monomers by low concentrations of palmitoyl-CoA.