Casazza J P, Felver M E, Veech R L
J Biol Chem. 1984 Jan 10;259(1):231-6.
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.
给3只先前在饮用水中摄入1%丙酮（体积/体积）的大鼠腹腔注射5微摩尔丙酮/克体重，结果血清中出现16±2纳摩尔/毫升的1,2 - 丙二醇和8±1纳摩尔/毫升的2,3 - 丁二醇。在未事先在饮用水中添加丙酮而注射丙酮或生理盐水的动物血清中，以及在饮用含1%丙酮的水后注射生理盐水的动物血清中，未检测到1,2 - 丙二醇或2,3 - 丁二醇。这些数据表明，丙酮既能诱导一种或多种关键酶，又可作为生成1,2 - 丙二醇的前体。从这些数据还可清楚看出，长期喂食丙酮在大鼠2,3 - 丁二醇的生成中起作用。从饮用添加1%丙酮的水的动物肝脏中分离出的微粒体含有两种先前未报道的酶活性，即把丙酮转化为丙酮醇的丙酮单加氧酶和把丙酮醇转化为甲基乙二醛的丙酮醇单加氧酶。这两种活性都需要氧气和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）。在注射5微摩尔丙酮/克体重后，用丙酮预先处理使对照动物血清中的D - 乳酸从9纳摩尔/毫升±9纳摩尔/毫升增加到喂食丙酮的动物的77±36纳摩尔/毫升。这与甲基乙二醛是丙酮代谢的副产物一致。提出了两条将丙酮转化为葡萄糖的途径，即甲基乙二醛途径和丙二醇途径。甲基乙二醛途径负责将丙酮转化为丙酮醇，丙酮醇转化为甲基乙二醛，以及随后甲基乙二醛转化为葡萄糖。丙二醇途径涉及通过一个尚不清楚的过程将丙酮醇转化为L - 1,2 - 丙二醇。L - 1,2 - 丙二醇由乙醇脱氢酶转化为L - 乳醛，L - 乳醛由醛脱氢酶转化为L - 乳酸。这些代谢途径在大鼠中的表达似乎取决于丙酮对丙酮单加氧酶和丙酮醇单加氧酶的诱导作用。
