Mitochondrial dysfunction in alcoholic patients as assessed by breath analysis.
Mitochondria of patients with alcoholic liver disease are morphologically abnormal, and mitochondria isolated from animals exposed to ethanol exhibit functional deficiencies in vitro. Because the functional consequences of the morphological alterations and the relevance of in vitro observations to mitochondrial function in alcoholic subjects are not clear, we assessed mitochondrial function noninvasively with a breath test. Mitochondrial function was assessed by measuring the exhalation of 14CO2 after administration of 1 microCi 2-keto[1-14C]isocaproic acid, the decarboxylation of which occurs in mitochondria. The results of the 2-keto[1-14C]isocaproic acid breath test in 17 alcoholic subjects were compared with the results in healthy controls and patients with nonalcoholic liver disease. The peak exhalation of 14CO2 and the fraction of the administered dose decarboxylated in 60 min were significantly lower in alcoholic patients than in healthy controls or patients with nonalcoholic liver disease. In alcoholic patients 2-keto[1-14C]isocaproic acid decarboxylation was impaired in the presence of normal conventional and quantitative liver function as assessed by aminopyrine breath test and galactose elimination capacity, indicating that 2-keto[1-14C]isocaproic acid decarboxylation does not simply reflect decreased functional liver mass. We conclude that mitochondrial function as reflected by 2-keto[1-14C]isocaproic acid decarboxylation is impaired in chronic alcoholic patients. The functional impairment is specific for excessive ethanol consumption and not a reflection of decreased global liver function or the presence of cirrhosis. 2-Keto[1-14C]isocaproic acid decarboxylation could thus be useful as a marker of excessive ethanol consumption.
Lauterburg
B H
BH
Department of Clinical Pharmacology, University of Bern, Switzerland.
Liang
D
D
Schwarzenbach
F A
FA
Breen
K J
KJ
D000328:Adult; D000437:Alcoholism / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D001944:Breath Tests; D003653:Decarboxylation; D005260:Female; D006801:Humans; D007651:Keto Acids / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000378:metabolism / Q000502:physiology*
D007651:Keto Acids; C013082:alpha-ketoisocaproic acid