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.