The formation of acetoacetate in homogenates of the mammary gland

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Abstract
Conditions affecting the balance between ketogenesis and lipogenesis in actively respiring homogenates of the lactating mammary gland of the guinea pig were studied. (carboxy-C14) Acetate and (2-C14) pyruvate, when incubated with mammary homogenates in the absence of added fumarate, were oxidized to CO2 and converted into acetoacetate at comparable rates. The addition of fumarate in increasing amounts (1-10 mM), which, as previously shown (Terner, C (1956). Biochem. J. 64, 532), results in the progressive stimulation of fatty acid synthesis, caused a progressive inhibition of acetoacetate formation. When unlabeled glucose was added to mammary homogenates metabolizing (carboxy-C14) acetate in the absence of fumarate, it did not suppress and in some experiments promoted the incorporation of acetate carbon into acetoacetate. In the presence of both glucose and fumarate the formation of acetoacetate was abolished. In marked contrast with the rapid rate of acetoacetate formation from acetate and from pyruvate, (C14) glucose (randomly labelled) or (2-C14) acetate gave rise to only small amounts of the ketone body. It is suggested that this difference resides in the ability of glucose and lactate to regenerate reduced pyridine nucleotide. The ability to maintain, in a vigorously oxidative system, conditions favorable for reductive reactions may be a common factor underlying not only the effects of fumarate on ketogenesis and lipogenesis in the present system, but also the well-known (antiketogenic properties of glucose and its stimulant action on lipogenesis.