Glycogenolysis and glycogen synthesis

Glycogen is formed from glucose 1-phosphate in two steps catalysed by UDPglucose pyrophos-phorylase (reaction 3.11) and glycogen synthase (reaction 3.12), and it is degraded by phosphorolysis catalysed by phosphorylase (reaction 3.13). 

These enzymes and their control mechanisms have been studied intensively in liver and skeletal muscle, since these are the main sites of glycogen 

Protein phosphatase-1 has been purified from the myofibrils of the domestic fowl gizzard (Alessi et al., 1992). It comprises three subunits (130, 37 and 20 kDa) and is probably a heterotrimer. The 37 kDa subunit is the catalytic subunit, and the others are regulatory subunits. The regulatory subunits enhance the catalytic activity towards meromyosin but suppress activity against phosphorylase, phosphorylase kinase and glycogen synthase. Two protein 

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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. 

The final step in signal transduction is the action of cAMP on the regulatory subunit of the enzyme, protein kinase A. This ubiquitous enzyme then phosphorylates and activates enzymes with functions specific to different cells and organs. In fat cells, protein kinase A activates lipase, which mobilizes fatty acids in muscle and liver cells, it regulates glycogenolysis and glycogen synthesis. 

Since phosphorylase kinase not only activates phosphorylase, but also phospho-rylates glycogen synthase thereby decreasing its activity, the regulation of phosphorylase kinase by calcium may also provide a mechanism for co-ordinating the rates of glycogenolysis and glycogen synthesis during muscle contraction. 

The role of the kinases is to phosphorylate and thus activate enzymes with functions specific to the particular cell or organ in question. For example, a protein kinase would activate lipase enzymes in fat cells, whereas in muscle and liver cells enzymes involved in glycogenolysis and glycogen synthesis are regulated through an even... 

The liver uses two mechanisms for endogenous glucose production, the mobilization of intracellular glycogen (glycogenolysis) and the synthesis of glucose from noncarbohydrate precursors (gluconeogenesis). 

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. 

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

In addition to inhibition of glycogenolysis, glucose also activates glycogen synthase and hence stimulates glycogen synthesis and this is achieved by an even more intriguing... 

The decreased insulin/glucagon ratio leads to inhibition of glycogen synthesis and increased glycogenolysis to supply some of the body s glucose needs on an immediate basis. 

Glycogen stores are regulated by a balance between glycogen synthesis (glycogenesis) and breakdown (glycogenolysis). 

Which one of the following is characteristic of low insulin levels A. Increased glycogen synthesis B. Decreased gluconeogenesis from lactate C. Decreased glycogenolysis D. Increased formation of 3-hydroxybutyrate E. Decreased action of hormone-sensitive lipase Correct answer = D. 3-hydroxybutyrate—a ketone body—synthesis is enhanced in the liver by taw insulin levels, which favor activation of hormone-sensitive lipase and release of fatty acids from adipose tissue. Glycogen synthesis is decreased, whereas gluconeogenesis is increased. 

In addition, there are numerous effects of insulin, generally anabolic, not mediated through its well-known effects on glucose transport. For example, in muscle, insulin decreases glycogenolysis and proteolysis. Lipolysis is inhibited by insulin in adipocytes. The effect of insulin on hepatic tissue is to promote increased glycogen production and protein synthesis and to inhibit glycogenolysis, proteolysis, lipolysis, and gluconeogenesis (Fig. 10-1). 

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