Assessment of mitochondrial function in vivo with a breath test utilizing α—ketoisocaproic acid
✍ Scribed by Patrice A. Michaletz; Ludèk Cap; Elliot Alpert; Bernhard H. Lauterburg
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 450 KB
- Volume
- 10
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
A breath test to assess hepatic mitochondrial function in vivo was evaluated in rats. Following the i.p. administration of [ l-'4C]-a-ketoisocaproic acid, 14C0, exhalation reached a peak within 10 to 20 min and then declined exponentially, with a half-life of 14.3 min. Control animals exhaled 38.6% of the administered radioactivity within 1 hr. In functionally anhepatic animals, I4CO2 in breath amounted to 23% of that in control animals, indicating that a-ketoisocaproic acid decarboxylation reflects mainly hepatic mitochondrial function in vivo. Ethanol (3 gm per kg) significantly decreased a-ketoisocaproic acid decarboxylation (21.8% of the dose appearing in breath in 1 hr), probably due to the ethanol-induced shift in the NAD':NADH ratio. In contrast, an uncoupler of mitochondrial respiration, sodium salicylate (375 mg per kg), increased the decarboxylation of a-ketoisocaproic acid (56.3% of the dose recovered as I4CO2 in 1 hr). Mitochondrial damage induced by 4-pentenoic acid decreased the decarboxylation of a- ketoisocaproic acid but did not affect the microsomal metabolism of antipyrine. The present data indicate that the a-ketoisocaproic acid breath test provides a noninvasive estimate of hepatic mitochondrial function in vivo which, when applied to man, might yield clinically useful information.
Mitochondrial dysfunction occurs in alcoholic liver disease (1, 2), Reye's syndrome (3) and cirrhosis (4, 5). Since the capacity of mitochondria to synthesize ATP may be of importance for the prognosis of patients with chronic liver disease, an estimate of mitochondrial function in patients with liver disease might be of clinical value. Preferentially, such an assessment of mitochondrial function should be obtained by noninvasive means.
Noninvasive tests based on breath analysis are used clinically and experimentally to quantitate certain aspects of hepatic function. The metabolism of 14C-labeled galactose to 14C02 provides an estimate of the functioning liver cell mass (6, 7), like the determination of the galactose elimination capacity calculated from the