Hypoxia causes glycogenolysis without an increase in percent phosphorylase a in rat skeletal muscle.
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)
Ren
J M
JM
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Gulve
E A
EA
Cartee
G D
GD
Holloszy
J O
JO
D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives; D005958:Glucosephosphates / Q000378:metabolism / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D007291:Inosine Monophosphate / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism*; D009994:Osmolar Concentration; D010758:Phosphorus / Q000378:metabolism; D010762:Phosphorylase a / Q000378:metabolism*; D010763:Phosphorylase b / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D005958:Glucosephosphates; D007291:Inosine Monophosphate; D010758:Phosphorus; C015785:2-deoxyglucose-6-phosphate; D000249:Adenosine Monophosphate; D019298:Glucose-6-Phosphate; D006003:Glycogen; D010762:Phosphorylase a; D010763:Phosphorylase b; D004837:Epinephrine