NMR Investigation of the Futile Cycling of Ethanol in Chronic Alcoholic Rats

Weight gain efficiency differences previously reported between alcohol-fed rats and their controls were investigated. Additionally, the futile cycling of ethanol proposed to explain such differences was studied by NMR spectroscopy. Male Sprague-Dawley rats were fed a nutritionally adequate diet containing 36% of the calories as alcohol, and their paired controls were fed an isocaloric diet for 1 f weeks to establish conditions of chronic alcohol feeding. Normalized metabolic efficiencies varied significantly during the initial 2-week period (6.86 ± 0.51 vs. 2.83 ± 0.18 g/kcal × 10⁻²) for control and alcohol-fed groups, respectively, and to a lesser extent over the entire feeding period (6.41 ± 0.78 vs. 4.60 ± 0.27 g/kcal × 10⁻²) for control and alcohol-fed groups, respectively. Alcohol-induced weight gain inefficiency in metabolism has previously been studied and explained by a variety of different biochemical and physiological mechanisms. One possible pathway of energy wastage may occur due to ethanol futile cycling from ethanol to acetaldehyde through the microsomal ethanol oxidation system pathway, and simultaneously from acetaldehyde to ethanol via the ADH pathway. This futile cycle represents a net loss of 6 ATP/cycle, corresponding to the loss of two reducing equivalents (NADH and NADPH). 1H NMR spectroscopy was used to test for this cycling in blood extracts after administration of 1,1-²H₂ ethanol. No futile cycling was detected either during the initial 2 weeks of feeding or after the entire feeding period.