Leucine and alpha-ketoisocaproate metabolism and interconversions in fed and fasted sheep

Fed and three-day-fasted sheep were infused with [1-14C] alpha-ketoisocaproate (KIC), L-[1-14C] leucine, and [14C] bicarbonate for determination of their whole-body turnovers, interconversions, and oxidation. Protein synthesis (PS), protein degradation (PD), net tissue metabolism, unidirectional utilization, and production rates also were estimated for the portal-drained viscera, liver, and hindquarters. KIC and leucine arterial concentrations (6.5 and 95 mumol X L-1) both increased with fasting. KIC turnover (9 mumol X min-1) also increased but leucine turnover (108 mumol X min-1) decreased. About 40% of KIC and 15% of leucine were oxidized, but they contributed less than 1% of whole-body CO2 production. The portal-drained viscera released KIC and leucine into the blood only in fed sheep. Hepatic net utilization of KIC and leucine (approximately 2 and 12 mumol X min-1) changed only little with fasting; thus, total splanchnic tissues utilized both in fasted sheep. Net metabolism by the hindquarters (representative of skeletal muscle) was always opposite to splanchnic metabolism. Thus, muscle must produce both KIC and leucine during fasting. In fed sheep whole-body PS, expressed as mumol X min-1 of leucine, was 92 +/- 6 and PD was 71 +/- 5. After fasting, PS decreased by 27%. Calculated liver protein metabolism was unaffected by the fast; PS (fixed and plasma) remained at about 25 and PD at about 15 mumol X min-1. However, protein metabolism by the hindquarters was sensitive to fasting; PS decreased from 30 +/- 4 in fed sheep to 20 +/- 3 mumol X min-1 after fasting and PD increased from 27 +/- 2 to 35 +/- 6 mumol X min-1. Thus, hepatic PS was maintained at the expense of muscle. If the total muscle mass of the body is considered, muscle PS contributed more than one half of whole-body PS.