Evidence for reverse flux through pyruvate kinase in skeletal muscle

Abstract

Jin ES, Sherry AD, Malloy CR. Evidence for reverse flux through pyruvate kinase in skeletal muscle. Am J Physiol Endocrinol Metab 296: E748 -

Chronic Post-Exercise Lactate Administration with Endurance Training Increases Glycogen Concentration and Monocarboxylate Transporter 1 Protein in Mouse White Muscle

“…One is the pathway by which pyruvate is directly converted into PEP. This pathway of reverse flux through pyruvate kinase is supported by previous studies (7,8). The other is the pathway by which lactate is converted into oxaloacetate by pyruvate carboxylase and then oxaloacetate is converted into PEP by PEP carboxylase (PEPCK).…”

Lactate Contributes to Glyceroneogenesis and Glyconeogenesis in Skeletal Muscle by Reversal of Pyruvate Kinase

“…The details of the involved pathways, however, are not clear. Although cytosolic PEPCK was suggested as a reaction step for glyceroneogenesis (15, 16), we did not detect any PEPCK activity in muscle (8). The roles of some other enzymes in skeletal muscle such as pyruvate carboxylase and glycerol kinase are not well established either (13,(17)(18)(19)(20)(21).…”

“…Sample Processing for NMR Analysis-Glycogen was extracted from muscle tissues, purified, and hydrolyzed as described previously (8). Blood was deproteinized by adding cold perchloric acid to a final concentration of 7% by volume.…”

“…In a previous study we found minimal labeling in carbons 1-3 of glutamate isolated from skeletal muscle of animals received [U- 13 C 3 ]lactate and concluded that the observed 13 C distribution in glucosyl units of glycogen was most consistent with reversal of PK (8). The study was performed in isolated muscle tissue and in intact animals using supra-physiological levels of lactate enriched with 13 C. In general, lactate concentration is ϳ1-2 mM in blood, but it can reach Ͼ10 mM after intense exercise (9,10).…”

“…2D and 7A). In contrast, the NMR spectra of these same metabolites isolated from fasted animals showed a slightly higher fraction of [2,[3][4][5][6][7][8][9][10][11][12][13] C 2 ]glutamate compared with [2,3-13 C 2 ]aspartate (Fig. 7B).…”