Liver glycogen synthesis

The first studies dealing with the effect of orotic acid on the ultrastructure and enzyme level in the liver [409-415], bile secretion [416], liver regeneration [417], and liver glycogen synthesis [418-420] have been performed in the last 10-15 years. Recently, an abnormal metabolism of orotic acid associated with acute hyperammonaemia [421], renal gluco-neogenesis in orotic acid fed rats [422], and the action of orotic acid on enchondral ossification [423] have also been studied. 

Insulin a polypeptide hormone, M, 5,780 (bovine), synthesized in, and secreted by, the B cells of the islets of Langerhans. The first protein primary sequence ever to be elucidated was that of I. (Fig.l) [F. Sanger etal. Biochem. J. 59 (1955) 509-518], I. is the only hormone that decreases the blood glucose concentration. It affects the entire intermediary metabolism, especially of the liver, adipose tissue and muscle. I. increases the permeability of cells to monosaccharides, amino aci and fatty acids, and it accelerates glycolysis, the pentose phosphate cycle, and, in the liver, glycogen synthesis. It promotes the biosynthesis of fatty adds and proteins. These indirect effects on various enzymes and metabolic processes are listed in the tables. 

Even though acetate units, such as those obtained from fatty acid oxidation, cannot be used for net synthesis of carbohydrate in animals, labeled carbon from " C-labeled acetate can be found in newly synthesized glucose (for example, in liver glycogen) in animal tracer studies. Explain how this can be. Which carbons of glucose would you expect to be the first to be labeled by "Relabeled acetate ... 

Liver Activation of glycogen synthesis Activation of glycogen synthase (GS) Inactivation of glycogen synthase kinase 3 (GSK3) through phosphorylation by Akt... 

Regulation of glycogen synthesis and degradation is essentially the same in the liver and muscle, but there are a couple of wrinkles. Glycogen degradation is also activated in muscle in response to the rise in intracellular calcium levels that accompanies contraction. This is achieved by... 

McArdle s disease is associated with excessive deposits of glycogen in muscle, and Hers disease with its deposition in liver. In both cases phosphorylase levels in the affected tissues are very low. In spite of this, glycogen synthesis is unimpaired, which is incompatible with glyco-genesis occurring through the action of phosphorylase. 

Glycogen phosphorylase isoenzymes have been isolated from liver, brain and skeletal muscle. All forms are subject to covalent control with conversion of the inactive forms (GP-b) to the active forms (GP-a) by phosphorylation on specific serine residues. This phosphorylation step, mediated by the enzyme phosphorylase kinase, is initiated by glucagon stimulation of the hepatocyte. Indeed, the same cAMP cascade which inhibits glycogen synthesis simultaneously stimulates glycogenolysis, giving us an excellent example of reciprocal control. 

Glycogenolysis and glycogen synthesis P-oxidation of fatty acids transamination and deamination of amino acids Cori cycle and glucose-alanine cycle, which recycles substrates between muscle and liver. 

Glucagon stimulation of liver cells in particular leads to phosphorylation of regulatory enzymes whereas insulin has the opposite effect. So, after a meal, we would expect glycolysis and glycogen synthesis to operate very efficiently so the control enzymes will be dephosphorylated. 

Glycogen deposits in the liver (glucose 6-P stimulates glycogen synthesis, and glycogenolysis is inhibited)... 

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