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Title: Assessment of mitochondrial function in vivo with a breath test utilizing alpha-ketoisocaproic acid

Abstract

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.

Authors:
; ; ;  [1]
  1. Baylor College of Medicine, Houston, TX (USA)
Publication Date:
OSTI Identifier:
5021704
Resource Type:
Journal Article
Journal Name:
Hepatology; (USA)
Additional Journal Information:
Journal Volume: 10:5; Journal ID: ISSN 0270-9139
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 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; 560300* - Chemicals Metabolism & Toxicology; 550201 - Biochemistry- Tracer Techniques

Citation Formats

Michaletz, P A, Cap, L, Alpert, E, and Lauterburg, B H. Assessment of mitochondrial function in vivo with a breath test utilizing alpha-ketoisocaproic acid. United States: N. p., 1989. Web. doi:10.1002/hep.1840100513.
Michaletz, P A, Cap, L, Alpert, E, & Lauterburg, B H. Assessment of mitochondrial function in vivo with a breath test utilizing alpha-ketoisocaproic acid. United States. https://doi.org/10.1002/hep.1840100513
Michaletz, P A, Cap, L, Alpert, E, and Lauterburg, B H. 1989. "Assessment of mitochondrial function in vivo with a breath test utilizing alpha-ketoisocaproic acid". United States. https://doi.org/10.1002/hep.1840100513.
@article{osti_5021704,
title = {Assessment of mitochondrial function in vivo with a breath test utilizing alpha-ketoisocaproic acid},
author = {Michaletz, P A and Cap, L and Alpert, E and Lauterburg, B H},
abstractNote = {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.},
doi = {10.1002/hep.1840100513},
url = {https://www.osti.gov/biblio/5021704}, journal = {Hepatology; (USA)},
issn = {0270-9139},
number = ,
volume = 10:5,
place = {United States},
year = {Wed Nov 01 00:00:00 EST 1989},
month = {Wed Nov 01 00:00:00 EST 1989}
}