Witschi A, Mossi S, Meyer B, Junker E, Lauterburg B H
Department of Clinical Pharmacology, University of Bern, Switzerland.
Alcohol Clin Exp Res. 1994 Aug;18(4):951-5. doi: 10.1111/j.1530-0277.1994.tb00065.x.
Mitochondria of patients with alcoholic liver disease exhibit structural abnormalities, and mitochondria isolated from animals exposed to ethanol are functionally deficient when studied in vitro. To assess possible functional consequences of these ethanol-associated alterations in vivo, we measured mitochondrial function in alcoholics noninvasively with a breath test. A mitochondrial function, the decarboxylation of ketoisocaproate (KICA), was assessed by measuring the exhalation of 13CO2 following the administration of 1 mg/kg 2-keto[1-13C]isocaproic acid, the decarboxylation of which occurs in mitochondria. The results of the KICA breath test in 12 alcoholic subjects were compared with the results in healthy controls and patients with nonalcoholic liver disease. The peak exhalation of 13CO2 and the fraction of the administered dose decarboxylated in 120 min were both significantly lower in alcoholics than in healthy controls and patients with nonalcoholic liver disease. In alcoholics, KICA decarboxylation was impaired in the presence of normal quantitative liver function tests such as the aminopyrine breath test and galactose elimination capacity, indicating that KICA decarboxylation does not simply reflect a decreased functional hepatic mass. The enrichment of circulating KICA with [13C]KICA was similar in alcoholics and controls, indicating that a decreased bioavailability or an increased dilution of labeled KICA cannot account for the decreased exhalation of 13CO2. It is concluded that mitochondrial function as reflected by KICA decarboxylation is impaired in chronic alcoholics. The functional impairment is specific for ethanol abuse and not a reflection of decreased global hepatic function. KICA decarboxylation could thus be useful as a marker for excessive ethanol consumption.
酒精性肝病患者的线粒体呈现结构异常，并且从暴露于乙醇的动物中分离出的线粒体在体外研究时功能存在缺陷。为了评估这些与乙醇相关的改变在体内可能产生的功能后果，我们通过呼吸测试对酗酒者的线粒体功能进行了非侵入性测量。一种线粒体功能，即酮异己酸（KICA）的脱羧作用，通过在给予1mg/kg 2-酮[1-13C]异己酸后测量13CO2的呼出量来评估，其脱羧作用发生在线粒体中。将12名酗酒受试者的KICA呼吸测试结果与健康对照者和非酒精性肝病患者的结果进行比较。酗酒者呼出的13CO2峰值以及在120分钟内脱羧的给药剂量分数均显著低于健康对照者和非酒精性肝病患者。在酗酒者中，在诸如氨基比林呼吸测试和半乳糖清除能力等肝功能定量测试正常的情况下，KICA脱羧作用受损，这表明KICA脱羧作用并非简单地反映功能性肝质量的降低。酗酒者和对照者中循环KICA用[13C]KICA的富集情况相似，这表明标记的KICA生物利用度降低或稀释增加并不能解释13CO2呼出量的减少。结论是，KICA脱羧作用所反映的线粒体功能在慢性酗酒者中受损。这种功能损害是乙醇滥用所特有的，并非全球肝功能降低的反映。因此，KICA脱羧作用可作为过量乙醇摄入的标志物。
