Formation of propionate after short-term ethanol treatment and its interaction with the carnitine pool in rat
Formation of propionate after short-term ethanol treatment and its interaction with the carnitine pool in rat
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DOI：
10.1016/s0741-8329(99)00036-1
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发表时间：
1999-10-01
期刊：
影响因子：
2.3
通讯作者：
Rizza, V
中科院分区：
文献类型：
--
作者：
Calabrese, V;Rizza, V
有机酸尿症是线粒体代谢的遗传性疾病，其导致有机酸在组织和生物体液中积累。已经证明，肉毒碱与细胞CoA库的相互作用，通过产生酰基-肉毒碱，对于在受损的酰基-CoA使用条件下维持正常的细胞代谢是潜在关键的，并且人类和其他哺乳动物暴露于乙醇效应导致线粒体功能受损。本研究的目的是评估乙醇对大鼠尿中短链有机酸和内源性肉毒碱排泄的作用。报告的数据显示，乙醇显著增加丙酸盐、甲基丙二酸盐以及游离乙酸盐、丁酸盐、丙酮酸盐、乳酸盐和β-羟基丁酸盐的尿排泄。此外，丙酸盐和甲基丙二酸盐形成的增加依赖于乙醇剂量;不需要乙醇代谢，如乙醇大鼠吡唑治疗实验所示;似乎是由β-肾上腺素能机制介导的，因为普萘洛尔几乎完全抑制丙酸盐蓄积。酒精管理也增加了特定的酰基-肉毒碱的排泄，对应于积累的酰基，而游离肉毒碱的排泄显着减少，相对于控制值。所提供的数据表明，短期乙醇给药与所选有机酸的排泄增加有关。本研究表明内源性肉毒碱库可能在对抗短链有机酸积累的有害效应中发挥作用。(C)1999 Elsevier Science Inc. All rights reserved.
Organic acidurias are genetic disorders of mitochondrial metabolism that lead to the accumulation in tissues and biological fluids of organic acids. It has been demonstrated that interaction of carnitine with the cellular CoA pool, through the production of acyl-carnitines, is potentially critical for maintaining normal cellular metabolism under conditions of impaired acyl-CoA use and that exposure of humans and other mammals to ethanol effects leads to impairment of mitochondrial function. The aim of the present study was to evaluate the role of ethanol on urinary excretion of short-chain organic acids and endogenous carnitines in rats. The data reported show that ethanol significantly increases urinary excretion of propionate, methylmalonate, as well as free acetate, butyrate, pyruvate, lactate, and P-hydroxybutyrate. Furthermore, the increased formation of propionate and methylmalonate was dependent on the dose of ethanol; did not require the metabolism of ethanol, as was shown in experiments with pyrazole treatment of ethanol rats; and appears to be mediated by beta-adrenergic mechanisms because propranolol almost completely suppresses propionate accumulation. Alcohol administration also increased excretion of specific acyl-carnitines, corresponding to the accumulating acyl groups, whereas excretion of free carnitine was significantly reduced, with respect to control values. The data presented indicate that the short-term ethanol administration is associated with increased excretion of selected organic acids. This study suggests that endogenous carnitine pool might play a role against the deleterious effects of accumulating short-chain organic acids. (C) 1999 Elsevier Science Inc. All rights reserved.