The effect of starvation in the rat on metabolite concentrations in blood,liver and skeletal muscle

The effects of starvation on the concentration of blood and tissue metabolites was determined at different times in rats starved up to 6 days.The concentration of the hepatic gluconeogenic intermediates: pyruvate, phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate, decreased by 50% by the third day and then gradually increased to control levels by the sixth day of starvation. The change in the concentration of these metabolites correlates inversely with the plasma free fatty acid levels and the -hydroxybutyrate: acetoacetate (B/A) ratios, suggesting that the increased generation of reducing equivalents from free fatty acid oxidation stimulate glyceraldehyde-phosphate dehydrogenase. However, this apparent stimulation does not appear to control glyconeogenic flux. The concentration of hepatic oxaloacetate increased gradually during starvation and correlated closely with the increase in hepatic gluconeogenic flux suggesting that the hepatic concentration of oxaloacetate may be important in controlling the rate of hepatic gluconeogenesis.The calculated equilibrium expression: alanine] -ketoglutarate]/pyruvate] glutamate] and aspartate] -ketoglutarate]/oxdaloacetate] glutamate] for alanine aminotransferase and aspartate amino transferase respectively, remained fairly constant in all the tissues studied throughout the starvation period, despite large changes in the concentrations of the individual reactants, indicating that these reactions are near equilibrium.The -hydroxybutyrate: acetoacetate (B/A) ratios, taken to reflect the mitochondrial redox state, increased more than 4-fold in liver and muscle after the first day of starvation. It decreased after the third day of starvation and returned close to prefasting levels by the sixth day. The change in B/A ratios in blood was similar to those observed in the organs, except that the magnitude of the change was less. The changes observed in the mitochondrial redox state during starvation correlate closely with the changes in plasma free fatty acid concentrations and with the rate of fatty acid oxidation.