1. In an attempt to define the importance of
acetate as a metabolic precursor, the activities of
acetyl-CoA synthetase (EC 6.2.1.1) and
acetyl-CoA hydrolase (Ec 3.1.2.1) were assayed in tissues from rats and sheep. In addition, the concentrations of
acetate in blood and liver were measured, as well as the rates of
acetate production by tissue slices and mitochondrial fractions of these tissues. 2.
Acetyl-CoA synthetase occurs at high activities in heart and kidney cortex of both species as well as in rat liver and the sheep masseter muscle. The
enzyme is mostly in the cytosol fraction of liver, whereas it is associated with the mitochondrial fraction in heart tissue. Both mitochondrial and cytosol activities have a K(m) for
acetate of 0.3mm.
Acetyl-CoA synthetase activity in liver was not altered by changes in diet, age or
alloxan-diabetes. 3.
Acetyl-CoA hydrolase is widely distributed in rat and sheep tissues, the highest activity being found in liver. Essentially all of the activity in liver and heart is localized in the mitochondrial fraction. Hepatic
acetyl-CoA hydrolase activity is increased by
starvation in rats and sheep and during the suckling period in young rats. 4. The concentrations of
acetate in blood are decreased by
starvation and increased by
alloxan-diabetes in both species. The uptake of
acetate by the sheep hind limb is proportional to the arterial concentration of
acetate, except in
alloxan-treated animals, where uptake is impaired. 5.
Acetate is produced by liver and heart slices and also by heart mitochondrial fractions that are incubated with either
pyruvate or palmitoyl-(-)-
carnitine. Liver mitochondrial fractions do not form
acetate from either substrate but instead convert
acetate into
acetoacetate. 6. We propose that
acetate in the blood of rats or starved sheep is derived from the hydrolysis of
acetyl-CoA. Release of
acetate from tissues would occur under conditions when the function of the tricarboxylic acid cycle is restricted, so that the circulating
acetate serves to redistribute oxidizable substrate throughout the body. This function is analogous to that served by
ketone bodies.