Phosphorylase a formation in protein-glycogen particles isolated from fast-twitch muscle of euthyroid and hypothyroid rats.
A fraction containing a protein-glycogen complex was isolated from rat skeletal muscle in order to study the effect of hypothyroidism on phosphorylase activation in this structural and functional unit of the glycogenolytic process. The total activities of phosphorylase and phosphorylase phosphatase in euthyroids and hypothyroids were the same in the fraction containing the protein-glycogen complex (P2 suspension). Hypothyroidism selectively lowered the maximal phosphorylase kinase activity in glycogen particles in the P2 suspension by 40%. Addition of Mg2+ (10 mM), ATP (2 mM), and Ca2+ (5 mM) rapidly stimulated phosphorylase b to a conversion resulting from phosphorylase kinase activation. Hypothyroidism reduced the rate of phosphorylase a formation by 50-70% in the P2 suspension. Glucose 6-phosphate (0.4-1.4 mM) inhibited the rate of phosphorylase a formation and this inhibition was similar for eu- and hypothyroids. There was a shift from 5.2 to 5.8 in the free Ca2+ concentration (pCaF) for half-maximal activation of phosphorylase in the P2 suspension of hypothyroids. A sixfold higher steady-state level of phosphorylase in euthyroids compared to hypothyroids was observed at a pCaF of 5.5. The Ca2+ sensitivity of the phosphorylase kinase, however, was not changed by hypothyroidism. These results provide further insight into the different time course of the phosphorylase activation in skeletal muscle during tetanic stimulation observed in euthyroidism and hypothyroidism (W. J. Leijendekker et al. (1985) Metabolism 34, 437-441).
Laboratory for Physiology, Free University, Amsterdam, The Netherlands.
W J
WJ
Leijendekker
P
P
Edauw
C
C
van Hardeveld
W S
WS
Simonides
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004789:Enzyme Activation; D006003:Glycogen / Q000302:isolation & purification / Q000378:metabolism*; D007037:Hypothyroidism / Q000201:enzymology*; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009132:Muscles / Q000201:enzymology*; D010764:Phosphorylase Kinase / Q000378:metabolism; D010765:Phosphorylase Phosphatase / Q000378:metabolism; D010762:Phosphorylase a / Q000378:metabolism*; D006005:Phosphorylases / Q000378:metabolism*; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013961:Thyroid Gland / Q000502:physiology*
D011506:Proteins; D006003:Glycogen; D010762:Phosphorylase a; D006005:Phosphorylases; D010764:Phosphorylase Kinase; D010765:Phosphorylase Phosphatase; D008274:Magnesium; D002118:Calcium