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Determination of gluconeogenesis in vivo with /sup 14/C-labeled substrates

Journal Article · · Am. J. Physiol.; (United States)
OSTI ID:5613133
A mitochondrial model of gluconeogenesis and the tricarboxylic acid cycle, where pyruvate is metabolized via pyruvate carboxylase and pyruvate dehydrogenase, and pyruvate kinase is examined. The effect of the rate of tricarboxylic acid flux and the rates of the three reactions of pyruvate metabolism on the labeling patterns from (/sup 14/C)pyruvate and (/sup 14/C)acetate are analyzed. Expressions describing the specific radioactivities and /sup 14/C distribution in glucose as a function of these rates are derived. Specific radioactivities and isotopic patterns depend markedly on the ratio of the rates of pyruvate carboxylation and decarboxylation to the rate of citrate synthesis, but the effect of phosphoenolpyruvate hydrolysis is minor. The effects of these rates on 1) specific radioactivity of phosphoenolpyruvate, 2) labeling pattern in glucose, and 3) contribution of pyruvate, acetyl-coenzyme A, and CO/sub 2/ to glucose carbon are illustrated. To determine the contribution of lactate or alanine to gluconeogenesis, experiments with two compounds labeled in different carbons are required. Methods in current use to correct for the dilution of /sup 14/C in gluconeogenesis from (/sup 14/C)pyruvate are shown to be erroneous. The experimental design and techniques to determine gluconeogenesis from /sup 14/C-labeled precursors are presented and illustrated with numerical examples.
Research Organization:
Cedars-Sinai Medical Center, Los Angeles, CA
OSTI ID:
5613133
Journal Information:
Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 248; ISSN AJPHA
Country of Publication:
United States
Language:
English