THE REGULATION OF GLYCOGEN-PHOSPHORYLASE AND GLYCOGEN BREAKDOWN IN HUMAN SKELETAL-MUSCLE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 518, 1-68
Abstract
The regulation of glycogen phosphorylase and glycogen breakdown in human skeletal muscle was investigated using the needle biopsy technique. The activity of phoshorylase in vitro was dependent upon the concentration of (Pi) used in the assay system. The Km of phosphorylase a for Pi was 26.2 mmol/l, and that of (a + b) (assayed in the presence of saturating AMP) was 6.8 mmol/l. Because of the differences in Km the apparent percentage of a to (a + b) activity varies with the Pi concentration used in the assay system. Phosphorylase a and (a + b) activities were adjusted to saturating Pi concentrations. The ratio of the activities in this case is independent of the Pi concentration and constitutes a minimal estimate of the fraction of phosphorylase molecules in the a form. The present results are in contrast to the classical theory which puts the emphasis on transformation as the main regulator of glycogen degradation. They suggest instead a central role of Pi. Thus, the low rates of glycogenolysis at rest and during epinephrine infusion are explained on the basis that the intracellular Pi concentration is low and limits the activity of the enzyme in vivo. The increased rate of glycogneolysis during ischemia, despite a decrease in the mole fraction of phosphorylase a, is explained by an increase in Pi resulting from the degradation of PCr [phosphocreatine]. The effect of increase in Pi from PCr breakdown is even more pronounced during exercise resulting in high glycogenolytic rates, aprpoaching the Vmax of the phosphorylase a fraction. The rate of glycogen degradation is a function of enzyme interconversion, substrate availability (particularly Pi) and allosteric regulation. In the present model the concentration of Pi in the muscle cells is of paramount importance to the regulation of phosphorylase activity and the glycogenolytic rate. During exercise increased Pi resulting from PCr breakdown serves as a link between energy demand and glycogen utilization.

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