Why Can't Animals Turn Fatty Acids Into Glucose?
Animals can’t turn fatty acids into glucose because fatty acids are metabolized 2 carbons at a time into the acetyl units of acetyl-CoA, and we have no enzymes to convert acetyl-CoA into pyruvate or any other metabolite in the gluconeogenesis pathway. Essentially, as I tell my students, the pyruvate dehydrogenase reaction is crossing the Rubicon: once it’s done, you can’t go back. The oxidative decarboxylation of pyruvate is irreversible, and there is no reverse bypass in animal cells. Acetyl-CoA of course enters the Krebs cycle, which ends with oxaloacetate, which is on the gluconeogenic pathway, but the Krebs cycle starts by reacting acetyl-CoA with OAA, and thus OAA production is balanced by OAA consumption: there is no net conversion of acetyl-CoA into OAA. Plants, fungi, and some microbes do have a way to do this: a bypass in the Krebs cycle called the glyoxylate cycle. Isocitrate, instead of being oxidized to alpha-ketoglutarate, is split into succinate and glyoxylate (HC(O)-COO), by an enzyme called isocitrate lyase. The glyoxylate reacts with another acetyl-CoA to form malate, in a reaction catalyzed by malate synthase. The succinate and malate both undergo their usua Continue reading >>