Muscle glycogen synthetase

Hepatic hexokinase Muscle glycogen synthetase Muscle phosphorylase Muscle hexokinase Muscle debranching enzyme... 

The possibility of inter-ionic and hydrophobic forces acting together to affect separation in some cases is likely. In a further publication, Shaltiel and Er-El [164] prepared a homologous series of co-aminoalkyl-agarose derivatives of the type, Sepharose-NH(CH2)n-NH2. When an extract of rabbit muscle was subjected to chromatography on these derivatives glycogen synthetase was not bound to n = 3 gels but was retained on 4-... 

In muscle and adipose tissue, insulin promotes transport of glucose and other monosaccharides across cell membranes it al.so facilitates tran.sport of amino icids, potassium ion.s. nucleosides, and ionic phosphate. Insulin also activates certain enzymes—kinases and glycogen. synthetase in muscle und adipose tissue. In adipose tissue, insulin decreases the release of fatty acids induced by epinephrine or glucagon. cAMP promotes fatty acid release from adipose ti.ssue therefore. it is pos.sible that insulin decreases fatty acid release by reducing tissue levels of cAMP. Insulin also facilitates the incorporation of intracellular amino acids into protein. 

D. If the phosphodiesterase that degrades cAMP were inhibited, cAMP levels would rise. Protein kinase A would become more active in the liver and muscle, pyruvate kinase would become less active, and glycogen synthetase activity would be decreased. 

Studies by Lamer and coworkers showed that 3 5 -cyclic AMP is an important factor that regulates the interconversion of the two forms of glycogen synthetase. The conversion of the independent into the dependent form is catalyzed by a kinase requiring ATP and Mg +, the activity of which is increased by cyclic AMP. Huijing and Lamer and others showed that muscle kinase appears to be similar to, but not identical with, phosphorylase b kinase, - and that the two enzymes seem to be equally sensitive to stimulation by cyclic AMP. It has been suggested - that cyclic AMP may in this instance act by increasing the affinity of an allosteric site for magnesium on the kinases. As epinephrine and other hormones increase the level of... 

The independent form can be converted into the dependent form by a difiFerent mechanism. It has been found that addition of calcium ions to certain glycogen synthetase preparations produces a conversion of the independent into the dependent form. This conversion does not involve ATP, and is not aflFected by adenosine 3 5 -cyclic phosphate it requires a protein similar to that involved in the activation of inactive phosphorylase b kinase by Ca ". Thus, calcium appears to exert an effect on the regulation of glycogen synthetase, and it is hypothesized that the inactivation of muscle glycogen synthetase after muscle contraction may be caused by this mechanism, mediated by an alteration of intracellular levels of Ca +. 

Fig. 15.3. Pathways of glycogen metabolism. 15.16, Glycogen synthetase (liver) 15.11, brancher enzyme 15.13, phosphorylase (liver) 15.15, phosphorylase kinase (liver) 15.12, phosphorylase (muscle) 15.10, debrancher enzyme (liver + muscle) 15.8, glu-cose-6-phosphatase (liver) 15.8a, glucose-6-phosphate translocase 15.5, fructose-1,6-di-phosphatase 15.9, a-glucosidase UDPGlc, uridine diphosphate glucose Glc-l-P, glucose-1-phosphate Glc-6-P, glucose-6-phosphate F-6-P, fructose-6-phosphate F-l,6-DiP, fructose- 1,6-diphosphate...

Stimulation of the synthesis of glycogen (section 5.5.3) from glucose in both liver and muscle, by activation of glycogen synthetase (section 10.5). 

APPLEMAN, M. M., BIRNBAUMER, L. and TORRES, H. N. (1966) Factors affecting the activity of muscle glycogen synthetase. III. 

Raising intracellular levels of cyclic AMP stimulates lipolysis in fat pads and isolated cells (4) probably by activating the triglyceride lipase. The nucleotide also stimulates the conversion of phosphorylase b to phosphorylase in muscle and the conversion of the I form of glycogen synthetase to the D form (5, 6). It thus seemed possible that the inhibitory action of insulin on these processes might be mediated by a fall in tissue levels of cyclic AMP. Accordingly we have examined the effect of insulin on cyclic AMP levels in epididymal fat pads incubated with epinephrine and caffeine in the absence of glucose. 

In summary we can say that insulin lowers cyclic AMP levels in adipose tissue and liver when the cyclic AMP has first been raised by various hormonal manipulations. This fall in cyclic AMP seems to account for several important actions of insxilin, in particular its action on lipolysis, glycogen synthetase and phosphorylase in adipose tissue, and on gluconeogenesis, glycogenolysis and potassium output by the liver. Glucose transport in adipose tissue does not seem to be controlled by the cyclic AMP level and we have no evidence that the action of insulin on muscle is mediated by cyclic AMP. 

Soderling, T. R., Hickenbottom, J. P., Reimann, E., Hunkeler, F. L., Walsh, D. A., and Krebs, E. G., 1970, Inactivation of glycogen synthetase and activation of phosphoryl-ase kinase by muscle adenosine 3, 5 -monophosphate-dependent protein kinases, /. Biol. Chem. 245 6317. 

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