AJP - Endocrinology and Metabolism, Vol 265, Issue 4 E636-E647, Copyright © 1993 by American Physiological Society

ARTICLES

14C-labeled propionate metabolism in vivo and estimates of hepatic gluconeogenesis relative to Krebs cycle flux

B. R. Landau, W. C. Schumann, V. Chandramouli, I. Magnusson, K. Kumaran and J. Wahren
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.

Purposes of this study were 1) to estimate in humans, using 14C-labeled propionate, the rate of hepatic gluconeogenesis relative to the rate of Krebs cycle flux; 2) to compare those rates with estimates previously made using [3-14C]lactate and [2-14C]acetate; 3) to determine if the amount of ATP required for that rate of gluconeogenesis could be generated in liver, calculated from that rate of Krebs cycle flux and splanchnic balance measurements, previously made, and 4) to test whether hepatic succinyl-CoA is channeled during its metabolism through the Krebs cycle. [2-14C]propionate, [3-14C]-propionate, and [2,3-14C]succinate were given along with phenyl acetate to normal subjects, fasted 60 h. Distributions of 14C were determined in the carbons of blood glucose and of glutamate from excreted phenylacetylglutamine. Corrections to the distributions for 14CO2 fixation were made from the specific activities of urinary urea and the specific activities in glucose, glutamate, and urea previously found on administering [14C]-bicarbonate. Uncertainties in the corrections and in the contributions of pyruvate and Cori cyclings limit the quantitations. The rate of gluconeogenesis appears to be two or more times the rate of Krebs cycle flux and pyruvate's decarboxylation to acetyl-CoA, metabolized in the cycle, less than one-twenty-fifth the rate of its decarboxylation. Such estimates were previously made using [3-14C]lactate. The findings support the use of phenyl acetate to sample hepatic alpha-ketoglutarate. Ratios of specific activities of glucose to glutamate and glucose to urinary urea and expired CO2 indicate succinate's extensive metabolism when presented in trace amounts to liver. Utilizations of the labeled compounds by liver relative to other tissues were in the order succinate = lactate > propionate > acetate. ATP required for gluconeogenesis and urea formation was approximately 40% of the amount of ATP generated in liver. There was no channeling of succinyl-CoA in the Krebs cycle in the hepatic mitochondria.

This article has been cited by other articles:

				J. G. Jones, M. A. Solomon, S. M. Cole, A. D. Sherry, and C. R. Malloy An integrated 2H and 13C NMR study of gluconeogenesis and TCA cycle flux in humans Am J Physiol Endocrinol Metab, October 1, 2001; 281(4): E848 - E856. [Abstract] [Full Text] [PDF]

				C. Agostoni, B. Carratu, C. Boniglia, E. Riva, and E. Sanzini Free Amino Acid Content in Standard Infant Formulas: Comparison with Human Milk J. Am. Coll. Nutr., August 1, 2000; 19(4): 434 - 438. [Abstract] [Full Text] [PDF]

				J. G. Jones, M. A. Solomon, A. D. Sherry, F. M. H. Jeffrey, and C. R. Malloy 13C NMR measurements of human gluconeogenic fluxes after ingestion of [U-13C]propionate, phenylacetate, and acetaminophen Am J Physiol Endocrinol Metab, November 1, 1998; 275(5): E843 - E852. [Abstract] [Full Text] [PDF]

				T. H. van Dijk, F. H. van der Sluijs, C. H. Wiegman, J. F. W. Baller, L. A. Gustafson, H.-J. Burger, A. W. Herling, F. Kuipers, A. J. Meijer, and D.-J. Reijngoud Acute Inhibition of Hepatic Glucose-6-phosphatase Does Not Affect Gluconeogenesis but Directs Gluconeogenic Flux toward Glycogen in Fasted Rats. A PHARMACOLOGICAL STUDY WITH THE CHLOROGENIC ACID DERIVATIVE S4048 J. Biol. Chem., July 6, 2001; 276(28): 25727 - 25735. [Abstract] [Full Text] [PDF]