Figure 4

Identification of a conserved metabolic network likely to be associated with alcohol sensitivity in flies and humans. Ethanol is converted via the alcohol dehydrogenase and aldehyde dehydrogenase reactions into acetate, which is subsequently conjugated to co-enzyme A (CoA; not shown). The biosynthetic pathway of co-enzyme A is schematically depicted in the red box. Acetyl-CoA produced in excess can be converted into fatty acids. The diagram highlights auxiliary pathways for the biosynthesis of fatty acids. The blue box illustrates how pyruvate carboxylase and malic enzyme mediate a cyclic metabolic pathway, which via the mitochondrial citrate and pyruvate transporters results in the net transport of acetyl-CoA across the mitochondrial membrane and generation of cytosolic NADPH, both critical substrates for fatty acid metabolism. An alternative metabolic pathway is the direct conversion of pyruvate into acetyl-CoA via the pyruvate dehydrogenase complex. This complex is inhibited through phosphorylation by pyruvate dehydrogenase kinase.