Glycogenolysis

The short-term or acute effects of the P-agonists may be different from chronic effects. Acute Hpolysis and glycogenolysis are not observed beyond the first day or two of treatment. Exact mechanisms of action on Hpid metaboHsm may differ among species. Chronic effects of the P-agonists reduce circulating insulin concentrations ST treatment causes an opposite change. Whereas residue levels may be of concern with adrninistration of several of the P-agonists, such is not the case for ST or GRE. 

CycHc adenosine monophosphate (cAMP), produced from ATP, is involved in a large number of ceUular reactions including glycogenolysis, Hpolysis, active transport of amino acids, and synthesis of protein (40). Inorganic phosphate ions are involved in controlling the pH of blood (41). The principal anion of interceUular fluid is HP (Pig. 3) (41). 

P-Adrenoceptors have been subdivided into P - and P2-adrenoceptors. A third subset called nontypical P-adrenoceptors or P -adrenoceptors have been described but are stiU the subject of debate. In terms of the interactions with various subsets of P-adrenoceptors, some antagonists are nonselective in that they antagonize the effects of activation of both P - and P2-adrenoceptors, whereas others are selective for either P - or P2-adrenoceptors. P - and P2-adrenoceptors coexist in almost all organs but generally, one type predominates. The focus herein is on the clinically relevant P -adrenoceptor-mediated effects on heart and on P2-adrenoceptor-mediated effects on smooth muscles of blood vessels and bronchioles, the insulin-secreting tissue of the pancreas, and skeletal muscle glycogenolysis for side effects profile (36). 

Metformin restrains hepatic glucose production principally by suppression of gluconeogenesis. The mechanisms involve potentiation of insulin action and decreased hepatic extraction of certain gluconeogenic substrates such as lactate. In addition, metformin reduces the rate of hepatic glycogenolysis and decreases the activity of hepatic glucose-6-phosphatase. Insulin-stimulated glucose uptake and glycogenesis by skeletal muscle is increased by metformin mainly by increased... 

These cascades of reactions need time in the range of seconds synaptic transmission through GPCRs is slow. All further postsynaptic changes depend on the type of postsynaptic cell. For example activation of 32-adrenoceptors causes in the heart an increase of the rate and force of contraction in skeletal muscle glycogenolysis and tremor in smooth muscle relaxation in bronchial glands secretion and in sympathetic nerve terminals an increase in transmitter release. 

Spriet, L.L., Soderlund, K., Bergstrom, M., Hultman, E. (1987b). Skeletal muscle glycogenolysis, glycolysis, and pH during electrical stimulation in men. J. Appl. Physiol. 62, 616-621. 

Pathways are compartmentalized within the cell. Glycolysis, glycogenesis, glycogenolysis, the pentose phosphate pathway, and fipogenesis occur in the cytosol. The mitochondrion contains the enzymes of the citric acid cycle, P-oxidation of fatty acids, and of oxidative phosphorylation. The endoplasmic reticulum also contains the enzymes for many other processes, including protein synthesis, glycerofipid formation, and dmg metabolism. 

Glucose 6-phosphate is an important compound at the junction of several metabolic pathways (glycolysis, gluconeogenesis, the pentose phosphate pathway, glycogenosis, and glycogenolysis). In glycolysis, it is converted to fructose 6-phosphate by phosphohexose-isomerase, which involves an aldose-ketose isomerization. 

GLYCOGENOLYSIS IS NOT THE REVERSE OF GLYCOGENESIS BUT IS A SEPARATE PATHWAY (Figure 18-1)... 

Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis by promoting the phosphorylytic cleavage by inorganic phosphate (phosphorylysis cf hy-... 

Glycogenolysis increases in muscle several hundred-fold immediately after the onset of contraction. This involves the rapid activation of phosphorylase by activation of phosphorylase kinase by Ca +, the same signal as that which initiates contraction in response to nerve stimulation. Muscle phosphorylase kinase has four... 

Not only is phosphorylase activated by a rise in concentration of cAMP (via phosphorylase kinase), but glycogen synthase is at the same time converted to the inactive form both effects are mediated via cAMP-dependent protein kinase. Thus, inhibition of glycogenolysis enhances net glycogenesis, and inhibition of glycogenesis enhances net glycogenolysis. Furthermore,... 

Figure 18-8. Coordinated control of glycogenolysis and glycogenesis by cAMP-dependent protein kinase. The reactions that lead to glycogenolysis as a result of an increase in cAMP concentrations are shown with bold arrows, and those that are inhibited by activation of protein phosphatase-1 are shown as broken arrows. The reverse occurs when cAMP concentrations decrease as a result of phosphodiesterase activity, leading to glycogenesis.

Glucose is also formed from liver glycogen by glycogenolysis (Chapter 18). 

Glucagon is secreted as a response to hypoglycemia and activates both glycogenolysis and gluconeogenesis in the liver, causing release of glucose into the blood. 

Gs Glucagon, 3-adrenergics T Adenylyl cyclase T Cardiac Ca +, CL, and Na+ channels Gluconeogenesis, lipolysis, glycogenolysis... 

Epinephrine stimulates glycogenolysis in skeletal muscle, whereas glucagon does not because of absence of its receptors. 

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