The glucose-6-phosphate dehydrogenase from Neisseria gonorrhoeae was inhibited by long-chain fatty acid acyl-coenzyme A derivatives. The inhibition was increased at low concentrations of glucose 6-phosphate and was greater with the NAD-linked activity (ca. 0.05 mM inhibitor required for 50% inhibition) than with the NADP-linked activity (ca. 0.2 mM required for 50% inhibition). Bovine serum albumin and spermine could prevent the inhibition by the acyl-coenzyme A derivatives, but neither of these compounds nor high concentrations of cofactors or substrate could reverse the effect. Dilution of enzyme–inhibitor preincubation mixtures appeared to reverse the inhibition. The inhibition by stearoyl-coenzyme A was of the mixed type, and the inhibitor appeared to have a greater affinity for the free enzyme (Ki = 0.016–0.05 mM) than for enzyme bound to cofactor or substrate (Kis = 0.07–0.08 mM). Glucose-6-phosphate dehydrogenase activity was also inhibited competitively by adenosine 5′-triphosphate and was strongly regulated by adenylate energy charge values between 0.9 and 1.0. Kinetic and other characteristics of the enzyme are presented, and the possible role of glucose-6-phosphate dehydrogenase as a target for fatty acid toxicity in gonococci, mediated in the form of the acyl-coenzyme A derivatives, is discussed.
Cloning and Characterization of Unusual Fatty Acid Desaturases from Anemone leveillei: Identification of an Acyl-Coenzyme A C20 Δ5-Desaturase Responsible for the Synthesis of Sciadonic Acid
