GLUTAMINE IS THE PREFERRED OXIDATIVE SUBSTRATE FOR SMALL INTESTINE OF SUCKLING RAT

Abstract

We determined the rate of oxidation of glutamine and β-hydroxybutyrate (βHβ), the preferred substrates in adult intestine, in developing rat. βHβ oxidation is low during the suckling period and increases four-fold at the time of weaning. In contrast glutamine oxidation is high during the suckling period and decreases at the time of weaning. Acetyl-CoA, an intermediate product of ketone oxidation is oxidized by intestinal mitochondria of suckling rat pups at 1/8 the rate of postwean indicating that tricarboxylic acid (TCA) cycle activity may be rate-limiting in βHβ oxidation to CO2 during the suckling period. A high mitochondrial (mito) [NADH]/[NAD] inhibits isocitrate dehydrogenase, a rate limiting step of the TCA cycle. The mito [NADH]/[NAD] decreases four fold at the time of weaning which is consistent with an increase in TCA cycle activity at this time. Since glutamine oxidation enters the TCA cycle in the form of α-ketoglutarate, the inhibition of isocitrate dehyrogenase by an increase in mito [NADH]/[NAD] would not affect glutamine oxidation. These data suggest that an increase in mito [NADH]/[NAD] results in inhibition of oxidation of substrates which enter the TCA cycle at the level of acetyl-CoA and results in the utilization of glutamine as a primary substrate during the suckling period.