Stimulation of skeletal muscle to contract activates
phosphorylase b-to-a conversion and glycogenolysis. Despite reversal of the increase in percentage of
phosphorylase a after a few minutes, continued
glycogen breakdown can occur during strenuous exercise.
Hypoxia causes sustained glycogenolysis in skeletal muscle without an increase in percentage of
phosphorylase a. We used this model to obtain insights regarding how glycogenolysis is mediated in the absence of an increase in percentage of
phosphorylase a.
Hypoxia caused a 70% decrease in
glycogen in epitrochlearis muscles during an 80-min incubation despite no increase in percentage of
phosphorylase a above the basal level of approximately 10%. Muscle Pi concentration increased from 3.8 to 8.6 mumol/g muscle after 5 min and 15.7 mumol/g after 20 min.
AMP concentration doubled, attaining a steady state of 0.23 mumol/g in 5 min. Incubation of oxygenated muscles with 0.1 microM
epinephrine induced an approximately sixfold increase in percentage of
phosphorylase a but resulted in minimal glycogenolysis. Muscle Pi concentration was not altered by
epinephrine. Despite no increase in percentage of
phosphorylase a,
hypoxia resulted in a fivefold greater depletion of
glycogen over 20 min than did
epinephrine. To evaluate the role of
phosphorylase b, muscles were loaded with
2-deoxyglucose 6-phosphate, which inhibits
phosphorylase b. The rate of glycogenolysis during 60 min of
hypoxia was reduced by only approximately 14% in
2-deoxyglucose 6-phosphate-loaded muscles.(ABSTRACT TRUNCATED AT 250 WORDS)