The metabolism of d(—)-β-hydroxybutyrate in sheep

Abstract

Sodium D(-)-[beta]-hydroxy[C14]butyrate was prepared by incubating sodium [Cl4]butyrate with sheep-liver slices or sheep-rumen epithelium in a bicarbonate medium. The products from [1-C14]- and [2-Cl4]-butyrate were labelled mainly (80-84%) in C-1 and C-2 respectively. Tissue preparations of rumen epithelium, liver, kidney, heart, spleen, muscle, brain and lung all showed some capacity to oxidize [beta]-hydroxybutyrate. Kidney, heart and spleen were the most active, and brain, liver and rumen epithelium the least active of the tissues. The endogenous respiration of isolated tissues was unaffected by added [beta]-hydroxybutyrate. Heart tissue oxidized [beta]-hydroxybutyrate more readily than the short-chain acids, and no mutual interactions were observed. Acetate and butyrate competed with [beta]-hydroxybutyrate as substrates for oxidation by kidney slices, but the oxidation of propionate was unchanged in the presence of [beta]-hydroxybutyrate. Glucose had little effect on the oxidation of [beta]-hydroxybutyrate by heart, kidney, brain and striated muscle, but glucose oxidation by these tissues was decreased by [beta]-hydroxybutyrate. Entry rates of [beta]-hydroxybutyrate were measured by isotope dilution with continuous-infusion techniques. The mean value for the entry rate of [beta]-hydroxybutyrate in 6 starved (24 hours) sheep was 0.68 (range 0.30-0.94) mg./min. Ag. body wt., and in two sheep starved for 5 days values of 0.53 and 0.92 mg/min.Ag were obtained. Comparison of the specific radioactivities of blood [beta]-hydroxybutyrate and blood observed during the terminal stages of [beta]-hydroxy-[2-C14]butyrate infusions provided a rough estimate of the contribution of [beta]-hydroxybutyrate to total oxidative metabolism. Values of 5 and 7% were obtained in 2 experiments.