Abstract
Intraperitoneal injection of 5 mumol of acetone/g, body weight, into 3 rats previously fed 1% acetone (v/v) in their drinking water resulted in the appearance in blood serum of 16 +/- 2 nmol of 1,2-propanediol/ml and 8 +/- 1 nmol of 2,3-butanediol/ml. No detectable 1,2-propanediol or 2,3-butanediol was found in the serum of animals after acetone or saline injection without prior addition of acetone to drinking water or in the serum of animals injected with saline after having been maintained on drinking water containing 1% acetone. These data suggest that acetone both acts to induce a critical enzyme or enzymes and serves as a precursor for the production of 1,2-propanediol. It is also clear from these data that chronic acetone feeding plays a role in 2,3-butanediol production in the rat. Microsomes isolated from the liver of animals maintained on drinking water supplemented with 1% acetone contained two previously unreported enzymatic activities, acetone monooxygenase which converts acetone to acetol and acetol monooxygenase which converts acetol to methylglyoxal. Both activities require O2 and NADPH. Prior treatment with acetone increased serum D-lactate from 9 nmol/ml +/- 9 nmol/ml in control animals to 77 +/- 36 nmol/ml in acetone-fed animals after injection with 5 mumol of acetone/g, body weight. This is consistent with methylglyoxal being a by-product of acetone metabolism. Two pathways for the conversion of acetone to glucose are proposed, the methylglyoxal and the propanediol pathways. The methylglyoxal pathway is responsible for the conversion of acetone to acetol, acetol to methylglyoxal, and the subsequent conversion of methylglyoxal to glucose. The propanediol pathway involves the conversion of acetol to L-1,2-propanediol by an as yet unknown process. L-1,2-Propanediol is converted to L-lactaldehyde by alcohol dehydrogenase, and L-lactaldehyde is converted to L-lactic acid by aldehyde dehydrogenase. Expression of these metabolic pathways in rat appears to be dependent on the induction of acetone monooxygenase and acetol monooxygenase by acetone.
Highlights
Intraperitoneal injection of 5 pmol ofacetone/g,body conversion of fat to carbohydrate
Microsomes isolated from the liverof animals maintained on drinking water supplemented with 1%acetone contained two previously unreported enzymatic activities, acetone monooxygenase which converts acetone to acetol and acetol monooxygenase which cona product of fatty acid catabolism, toglucose
Blood serum obtained from one human subject who had been fasted for 21 days was found to contain approximately 100 nmol/ml 1,2-propanediol and 16nmol/ml of acetol,’ both proposed intermediates of the pathway describedhere
Summary
From the Laboratory of Metabolism, National Instituteon Alcohol Abuse and Alcoholism,Rockuille, Maryland 20852. Their data suggest that uptotwo-thirds of thecirculating blood acetone may be converted to glucose This glucose production could account for 10% of the gluconeogenic demands of humans fasted 21 days [1]and suggests that acetone is an intermediate in the other protocol which results in the occurrence of both 1,2propanediol and2,3-butanediol in laboratory animals is in the literature. Blood serum obtained from one human subject who had been fasted for 21 days was found to contain approximately 100 nmol/ml 1,2-propanediol and 16nmol/ml of acetol,’ both proposed intermediates of the pathway describedhere. In animoafls1,2-propanediol and subsequent conversion to D- or L-lactic acid not given heparin, mixed arteriovenous samples of blood were col- by the actionof horse liver alcohol dehydrogenase and yeast aldehyde lected after decapitation. + + + + CH,-CO-CH, NADPH H+ 0 2 -+ CHS-CO-CHZOH NADP+ + H20
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