Metabolism of ketone bodies in pregnant sheep.

Abstract

A combination of isotope-dilution and arteriovenous-difference techniques was used to determine the significance of ketones to energy homoeostasis in fasted pregnant ewes. 2. There was incomplete interconversion of D(-) 3-hydroxybutyrate (3HB) and acetoacetate (AcAc) and therefore neither entry rate nor oxidation of total ketone bodies could be estimated by assuming circulating ketone bodies represent a single metabolic compartment. Total ketone body metabolism was satisfactorily summarized using a three-compartment model. In fasted pregnant ewes the mean entry rate of total ketones was 1 mmol/h per kg body-weight and of the ketones entering the circulating 87% were promptly oxidized to carbon dioxide accounting for 30% of the total CO2 production. 3. Ketone bodies are readily utilized by hind-limb skeletal muscle such that if completely oxidized, 18 +/- 4 and 48 +/- 3% of the oxygen utilized could be accounted for in fed and fasted pregnant ewes respectively. For both 3HB and AcAc there was a hyperbolic relationship between utilization and arterial concentration. The apparent Michaelis constant (Km) values were 0.55 and 1.42 mM respectively and the maximum velocity (Vmax) 2.9 and 5.6 mmol/h per kg muscle. The arterial concentration of AcAc is always below the Km value and this limits the utilization rate. THe D(-) 3HB concentration however, may surpass that required for maximum utilization and ketoacidosis may be a consequence of this. 4. A two-compartment model was used to analyse ketone body metabolism by hind-limb skeletal muscle. The results suggested substantial interconversion and production of AcAc and 3HB. 5. The pregnant uterus utilized 3HB which if completely oxidized accounted for 12 +/- 2 (fed) and 25 +/- 4 (fasted) % of its O2 consumption. At least 64% of the net 3HB utilized was oxidized. AcAc was not utilized in significant quantitites.