Pentose cycle flux and fatty acid synthesis in bovine adipose tissue slices incubated with 6-aminonicotinamide.
The effects of the purported inhibitor of 6-phosphogluconate dehydrogenase, 6-aminonicotinamide, on lipogenesis from acetate and the metabolism of glucose were investigated in bovine adipose tissue. The incorporation of [U-14C]acetate and tritium from [3-3H]glucose into fatty acids was stimulated by 6-aminonicotinamide proportionately, indicating that the pentose cycle provided the same percentage of NADPH required for fat synthesis in the absence and presence of 6-aminonicotinamide. Tissue samples incubated with 6-aminonicotinamide displayed higher maximal activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase than control samples. The cellular content of 6-phosphogluconate was increased by 6-aminonicotinamide by 40% in samples incubated with 2 mM glucose (plus 33 mU/ml insulin) and 10 mM acetate; 6-aminonicotinamide stimulated the production of L-lactate in either the absence or presence of acetate. Studies with 1-, 6-, and U-14C-labeled glucose indicated that 6-aminonicotinamide increased the proportion of utilized glucose metabolized by the pentose cycle in the absence, but not in the presence of acetate. Unlike results observed in rat adipose tissue, the primary effect of 6-aminonicotinamide was to increase the proportion of NADPH produced by the pentose cycle that was utilized for fat synthesis secondarily to the stimulation of lipogenesis by an unknown mechanism.
D015120:6-Aminonicotinamide / Q000494:pharmacology*; D000085:Acetates / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D005227:Fatty Acids / Q000096:biosynthesis*; D005947:Glucose / Q000378:metabolism; D005948:Glucose Dehydrogenases / Q000378:metabolism; D066298:In Vitro Techniques; D007773:Lactates / Q000032:analysis; D009249:NADP / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives*; D010429:Pentoses / Q000378:metabolism*; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism; D011336:Probability; D013268:Stimulation, Chemical
D000085:Acetates; D005227:Fatty Acids; D007773:Lactates; D010429:Pentoses; D009536:Niacinamide; D015120:6-Aminonicotinamide; D009249:NADP; D005948:Glucose Dehydrogenases; D010734:Phosphogluconate Dehydrogenase; D005947:Glucose