Quantitative assessment of pathways for lactate disposal in skeletal muscle fiber types

Quantifying the contribution of the various skeletal muscle fiber types toward lactate disposal has proven elusive. In part, this can be attributed to the lack of adequate preparations for the study of all potential metabolic pathways involved. Toward this end our laboratory developed several perfused muscle preparations that are homogeneous for specific fiber types. This paper briefly reviews our findings regarding the influence of fiber type on lactate disposal in resting skeletal muscle and the metabolic pathways involved. Perfusing over a range of lactate concentrations, 1-12 mM, all fiber types were shown to switch from net production at low lactate concentrations to net consumption at higher concentrations. This transition occurred at lower lactate concentrations for Type I and IIa fibers, when compared with IIb fibers. For Type I and IIa fibers oxidation was observed to be the primary route of disposal accounting for approximately 50% of the lactate removed. For all fiber types, transamination was a significant pathway for the disposal of lactate carbon, whereas glyconeogenesis was the primary pathway for disposal in Type IIb fibers. The glyconeogenic capacity was quantitatively similar for Type IIa and IIb fibers but was negligible for Type I fibers. The pathway for glyconeogenesis in skeletal muscle was shown to be substantially different from that employed in hepatic glyconeogenesis. Results indicated that neither the TCA cycle nor phosphoenolpyruvate carboxykinase is involved in skeletal muscle glyconeogenesis. Our findings suggested that PEP formation in skeletal muscle glyconeogenesis occurs by "reversal" of the pyruvate kinase reaction.