When cultured on a defined diet, ethanol was an efficient substrate for lipid synthesis in wild-type Drosophila melanogaster larvae. At certain dietary levels both ethanol and sucrose could displace the other as a lipid substrate. In wild-type larvae more than 90% of the flux from ethanol to lipid was metabolized via the alcohol dehydrogenase (ADH) system. The ADH and aldehyde dehydrogenase activities of ADH were modulated in tandem by dietary ethanol, suggesting that ADH provided substrate for lipogenesis by degrading ethanol to acetaldehyde and then to acetic acid. The tissue activity of catalase was suppressed by dietary ethanol, implying that catalase was not a major factor in ethanol metabolism in larvae. The activities of lipogenic enzymes, sn-glycerol-3-phosphate dehydrogenase, fatty acid synthetase (FAS), and ADH, together with the triacylglycerol (TG) content of wild-type larvae increased in proportion to the dietary ethanol concentration to 4.5% (v/v). Dietary ethanol inhibited FAS and repressed the accumulation of TG in ADH-deficient larvae, suggesting that the levels of these factors may be subject to a complex feedback control.

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Dietary sucrose and ethanol are potent modulators of sn-glycerol-3-phosphate dehydrogenase (GPDH) in the third instar larvae of Drosophila melanogaster. When added to modified Sang's medium C, 428 mM ethanol and 146 mM sucrose each increased the GPDH tissue activity more than 90% and GPDH cross-reacting material (CRM) more than 50% over the levels found in larvae fed the 14.6 mM sucrose control diet. When fed together, ethanol and sucrose exerted synergetic effects on GPDH activity and CRM. The activity of glycerol-3-phosphate oxidase was also stimulated by dietary ethanol and sucrose, indicating that the glycerol-3-phosphate cycle was operating in the larvae. Dietary ethanol caused similar shifts in the NADH:NAD+ ratio in wild-type and Gpdh null larvae, suggesting that the maintenance of the cofactor equilibrium is not the primary function of GPDH in larvae. Increases in triacylglycerol content associated with the administration of ethanol and sucrose to larvae suggested that the formation of glycerol-3-phosphate for use in lipid synthesis is an important function of GPDH in larvae. Because ethanol is a constituent of the natural diet of D. melanogaster, nutritional modulation of GPDH is postulated to be an important aspect of the adaptation of the species to its environment.