Production and utilization of acetate in mammals

Abstract

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.

De novo acetate production is coupled to central carbon metabolism in mammals

“…Acetate can be generated by the removal of acetyl groups from histones by histone deacetylases 20 and by hydrolysis of Ac-CoA 21 . We thus measured the concentrations of the metabolites involved in these processes and observed orders of magnitude lower concentrations of Ac-CoA than glucose-derived pyruvate, lactate, and acetate ( Fig.…”

Interrelationship in the Regulation of Pyruvate Dehydrogenase and Adenine-Nucleotide Translocase by Palmitoyl-CoA in Isolated Mitochondria

“…This could be modified by the activity of acetyl-CoA hydrolase, such interference would not substantially affect the 14C02 liberation from [l-14C]pyruvate. The activity, regulation and physiological significance of this enzyme has recently been discussed for liver [23] and adipose tissue [24]. Secondly, factors such as the amount of potassium in the medium and the pH of the medium may be critical as indicated by the studies of Hucho et al [25] who have shown differential effects of these parameters on the activities of pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase in kidney and heart.…”

Origin and utilization of volatile fatty acids in the rat

“…Only acetate is present in significant amounts in the peripheral blood of nonherbivores and at concentrations lower than in herbivores (R6m6sy and Demign6, 1974). Surprisingly, there is no evident difference in blood concentrations between fed and starved non-herbivores (Knowles et al, 1974). In the rat, the main site of VFA production and absorption is the large intestine, particularly the caecum (R6m6sy and Demign6, 1976).…”

“…In the rat, the main site of VFA production and absorption is the large intestine, particularly the caecum (R6m6sy and Demign6, 1976). Besides digestive origin, it has frequently been suggested that endogenous acetate could be produced by various tissues (Knowles et al, 1974 ;Seufert et a/., 1974 ;Buckley and Williatnson, 1977).…”