Metabolic adaptation in phosphorylase kinase deficiency. Changes in metabolite concentrations during tetanic stimulation of mouse leg muscles

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Abstract
Glycogen, nucleotides and glycolytic intermediates and products were measured before and during tetanus in the hamstrings-muscle groups of normal (C3H) and phosphorylase kinase-deficient (ICR/IAn) mice. Phosphorylase kinase-deficient muscles contained 3- to 4-fold more glycogen and sustained a larger (about 2-fold), more rapid (11 .+-. 2 ng/s faster) and more prolonged glycogenolysis during 120s tetanus, despite their lack of phosphorylase 2a. No significant change in total adenine nucleotide contents occurred during tetanus in either strain, but there was a 60- to 100-fold rise in IMP concentration to about 2 mM in both strains. The initial rate of IMP formation was 6-fold more rapid (112 nmol/s per g) in phosphorylase kinase-deficient muscle. Adenylosuccinate content rose to 36 nmol/g in phosphorylase kinase-deficient muscle and to 9 nmol/g in normal muscle at 45 s tetanus, but then fell. In phosphorylase kinase-deficient muscle, G-6-P, a powerful phosphorylase inhibitor, was 56% of that in normal muscle. The mass-action ratio of the phosphoglucomutase-catalyzed reaction [G-6-P]/[glucose 1-phosphate] was markedly lower than Keq. (about 17) in relaxed muscle of both strains (about 5-7), but rose significantly during tetanus to the value for Keq. The data for IMP satisfy the criteria put forward by Rahim, Perrett and Griffiths for a nucleotide activator of phosphorylase b: it should be present at a higher concentration in phosphorylase kinase-deficient muscle, its concentration should rise during muscle work, and it should attain a concentration comparable with its activation constant for phosphorylase b.