Assessment of mitochondrial function in vivo with a breath test utilizing alpha-ketoisocaproic acid
- Baylor College of Medicine, Houston, TX (USA)
A breath test to assess hepatic mitochondrial function in vivo was evaluated in rats. Following the i.p. administration of (1-{sup 14}C)-alpha-ketoisocaproic acid, {sup 14}CO{sub 2} 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, {sup 14}CO{sub 2} in breath amounted to 23% of that in control animals, indicating that alpha-ketoisocaproic acid decarboxylation reflects mainly hepatic mitochondrial function in vivo. Ethanol (3 gm per kg) significantly decreased alpha-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 alpha-ketoisocaproic acid (56.3% of the dose recovered as {sup 14}CO{sub 2} in 1 hr). Mitochondrial damage induced by 4-pentenoic acid decreased the decarboxylation of alpha-ketoisocaproic acid but did not affect the microsomal metabolism of antipyrine. The present data indicate that the alpha-ketoisocaproic acid breath test provides a noninvasive estimate of hepatic mitochondrial function in vivo which, when applied to man, might yield clinically useful information.
- OSTI ID:
- 5021704
- Journal Information:
- Hepatology; (USA), Vol. 10:5; ISSN 0270-9139
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ETHANOL
BIOLOGICAL EFFECTS
KETO ACIDS
DECARBOXYLATION
MITOCHONDRIA
BIOLOGICAL FUNCTIONS
BIOLOGICAL HALF-LIFE
CARBON 14 COMPOUNDS
IN VIVO
INTRAPERITONEAL INJECTION
LIVER
NAD
NADH2
RATS
RESPIRATION
TRACER TECHNIQUES
ALCOHOLS
ANIMALS
BODY
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHEMICAL REACTIONS
COENZYMES
DIGESTIVE SYSTEM
FUNCTIONS
GLANDS
HYDROXY COMPOUNDS
INJECTION
INTAKE
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
RODENTS
VERTEBRATES
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