1. The supply and utilisation of acetate has been estimated simultaneously in the whole animal and tissues of sheep using a combination of isotopedilution and arteriovenousdifference techniques. Animals were made alloxandiabetic and acetate metabolism was compared when stabilized to normal metabolite levels with insulin (ITA sheep) and when food and insulin had teen withdrawn for 36 h (fasted, diabetic sheep).2. Acetate was simultaneously produced and utilized by all tissues. The exogenous (or gut) supply of acetate was the most important determiniint of circulating acetate level. Endogenous acetate was produced mainly in the liver; 77 and 94% in fasted. diabe1.ic and ITA sheep respectively. The production of endogenous acetate remained fairly constant and was not related to ketogenesis, which supports the idea that circulating acetate is largely a product of fermentation. The liver, gut and muscle utilized 17,25 and 54% respectively (96% total) of the acetate entry rate in ITA sheep; a similar percentage utilization was found in fasted, diabetic sheep.3. Acetate is largely oxidized to carbon dioxide in the gut and muscles of sheep and may account for 3 0 4 0 % of their oxidative metabolism. This figure is similar to that for the whole animal. The total acetate taken up by the liver could account for 30% of the oxygen consumption; however, the liver may not directly oxidize all the utilized acetate.4. The over-all conclusion froin this study is that acetate is largely of dietary origin and the major factor determining its rate of utilization is the arterial concentration.

1. A combination of isotope-dilution and arterio-venous difference techniques was used to determine rates of leucine metabolism and protein synthesis and degradation in a hind-limb preparation (predominantly muscle) and the whole body of eight lambs fed on milk to appetite and eight lambs fasted from 24 to 48 h.2. Compared with fed lambs, fasted lambs showed decreased rates of protein synthesis in both whole body and hind-limb, and in hind-limb muscle, elevated rates of protein degradation.3. The effects of two rates of insulin infusion on whole-body and hind-limb-muscle leucine metabolism, and in turn on protein metabolism, were determined. Insulin had no significant effect on leucine flux or oxidation (and hence protein synthesis and degradation) in whole-body or hind-limb muscle of fed lambs. In fasted lambs insulin progressively reduced arterial leucine concentration and whole-body leucine flux and oxidation, indicating a reduction in both protein synthesis and degradation. Insulin reduced the rate of leucine efflux from hind-limb muscle, which was followed by a reduction in leucine uptake. Insulin increased hind-limb-muscle glucose uptake in both fed and fasted lambs.4 On the basis that hind-limb muscle was representative of skeletal muscle in general, we estimated that muscle accounted for the same percentage (about 27) of whole-body protein synthesis in both fed and fasted lambs. This percentage was unaffected by infusion of insulin, although the absolute rates differed in fed and fasted lambs.

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