HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Walter, P. Articles by Lardy, H. A. Search for Related Content PubMed PubMed Citation Articles by Walter, P. Articles by Lardy, H. A. Social Bookmarking                      What's this?

Paths of Carbon in Gluconeogenesis and Lipogenesis

III. THE ROLE AND REGULATION OF MITOCHONDRIAL PROCESSES INVOLVED IN SUPPLYING PRECURSORS OF PHOSPHOENOLPYRUVATE

From the ¹ From the Institute for Enzyme Research, University of Wisconsin, Madison, Wisconsin 53706

The activity of pyruvate carboxylase in rat liver mitochondria was estimated by measuring the ¹⁴CO₂ incorporation in the presence of pyruvate, adenosine triphosphate, magnesium, and inorganic phosphate. Malate, fumarate, and citrate were shown to be the main radioactive products. When glutamate was added to the system, radioactive aspartate was also formed. Oxalacetate accumulated in only minute amounts; it could not be trapped by enzymatic reactions outside the mitochondria. The amount of radioactive products was decreased by addition of creatine, and nearly abolished by glucose, when these were used as phosphoryl acceptors. About 40% of the incorporated ¹⁴CO₂ in malate and aspartate was found in carbon 1 of these compounds, demonstrating that a high degree of randomization of the label had occurred. Pyruvate carboxylation was inhibited by ADP. The inhibition could be overcome by addition of inorganic phosphate which removed ADP by oxidative phosphorylation. Excess ATP did not relieve the inhibition. Addition of caprylate to the system caused a strong inhibition of pyruvate decarboxylation and promoted the formation of radioactive malate and fumarate, whereas the accumulation of the other radioactive compounds was decreased. The data, together with previous information, indicate that phosphoenolpyruvate is synthesized from pyruvate by a pathway involving pyruvate carboxylation and formation of aspartate and malate inside the mitochondria, diffusion of these compounds into the cytosol, and their conversion to phosphoenolpyruvate via oxalacetate. The regulation of this pathway is discussed and a hypothesis as to how fatty acids could control gluconeogenesis is outlined.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. J. MacDonald, L. A. Fahien, L. J. Brown, N. M. Hasan, J. D. Buss, and M. A. Kendrick Perspective: emerging evidence for signaling roles of mitochondrial anaplerotic products in insulin secretion Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E1 - E15. [Abstract] [Full Text] [PDF]

				M. J. MacDonald, L. A. Fahien, J. D. Buss, N. M. Hasan, M. J. Fallon, and M. A. Kendrick Citrate Oscillates in Liver and Pancreatic Beta Cell Mitochondria and in INS-1 Insulinoma Cells J. Biol. Chem., December 19, 2003; 278(51): 51894 - 51900. [Abstract] [Full Text] [PDF]

				H. Lardy Happily at Work J. Biol. Chem., January 31, 2003; 278(6): 3499 - 3509. [Full Text] [PDF]

				M. J. MacDonald and M. J. MacDonald Feasibility of a Mitochondrial Pyruvate Malate Shuttle in Pancreatic Islets J. Biol. Chem., August 25, 1995; 270(34): 20051 - 20058. [Abstract] [Full Text] [PDF]