Butyrate Metabolism in the Lactating Cow S-

The possibility that butyrate may be glucogenic in ruminants has been suggested by several experimental studies. Intravenous injection of butyrate in sheep was followed by increased concentrations of blood sugar (1) and, in lambs, it was found that butyrate was more effective than propionate for alleviating insulin-induced hypoglycemia (2) ; acetate injection did not have a similar effect in either study. Later investigators (3-5) have reported that ruminants show a variable response in blood glucose level after butyrate injection. In an effort to account for this variability it has been suggested that a plethora of body glucose inhibited “gluconeogenesis from butyrate” (5) and that a state of acidosis interferes with “the glucogenic effect of butyrate” (6). Studies with (Y-labeled fatty acids have provided additional evidence for the apparently anomalous metabolic behavior of butyrate in ruminants. Intact cows injected with acetate-Cl4 transferred to milk fat 70% of the total Cl4 recovered from milk products; this demonstrates the lipogenic behavior of this fatty acid (7). Propionate-Cl4 was markedly glucogenic in the cow with 60 to 70% of the milk Cl4 in lactose (8). In contrast to these results, which are consistent with current concepts on the metabolic behavior of acetate and propionate in animals, when butyrate-1-V or butyrate-2-C14 was injected into lactating cows, approximately twice as much Cl4 was recovered from lactose and also from casein as was recovered in milk fat (9). Inasmuch as butyrate is a component of milk triglyceride and makes up about 10 per cent of the fatty acids on a molar basis (lo), one would expect butyrate to be a better precursor of milk fat. Studies in vitro have indicated a direct role for butyryl coenzyme A in fatty acid synthesis in animal tissues. Butyryl-CoA was reported to be the most effective of several acyl-CoA compounds tested, including acetyl-CoA, for stimulating the conversion of malonyl-CoA to long chain fatty acids by rat liver enzymes (11). It has also been observed that butyryl-CoA was a required component for the transfer of Cl4 from pyruvate to fatty acids by normal rat liver mitochondria and that it restored to normal the defective lipogenesis of liver mitochondria from alloxan-diabetic rats (12). The butyryl moiety of butyryl-CoA was incorporated intact into palmitic acid synthesized by pigeon liver (13, 14), and it was shown that the same enzymes and cofactors were required for the incorporation of Cl4 from either acetate or butyrate into long chain fatty acids (13). The demonstrated behavior of butyryl-CoA in animal tissues