| page 164 |  | | page 165 |
| Figure 12.5 Mechanism of activation of glycogenolysis in liver via the α-adrenergic receptor. Diacylglycerol (DAG) and inositol trisphosphate (IP3) are second messengers mediating the adrenergic response. Both DAG and PKC remain associated with the plasma membrane. PIP2, phosphatidylinositol bisphosphate; PKC, protein kinase C. See also Figures 38.8 and 38.9. |
The tissue localization of hormone receptors provides tissue specificity to hormone action. Only those tissues with glucagon receptors respond to glucagon. Muscle may be rich in glycogen, even during hypoglycemia, but it lacks both the glucagon receptor and Glc-6-Pase. Therefore muscle glycogen cannot be mobilized to replenish blood glucose . Muscle glycogenolysis is activated in response to epinephrine through the β-adrenergic receptor (cAMP-mediated), providing a supply of carbohydrate for the energy needs of muscle. This occurs not only during 'fight or flight' situations, but also during prolonged exercise. There are also two important hormone-independent mechanisms for activation of glycogenolysis in muscle (Fig. 12.6). First, the influx of Ca2+ into the muscle cytoplasm in response to nerve stimulation activates the basal, unphosphorylated form of phosphorylase
kinase by action of the Ca2+-calmodulin complex. This hormone-independent activation of phosphorylase provides for rapid activation of glycogenolysis during short bursts of exercise, even in the absence of epinephrine action. A second mechanism for activation of muscle glycogenolysis involves direct allosteric activation of phosphorylase by AMP. Increased usage of ATP during a rapid burst of muscle activity leads to rapid accumulation of ADP, which is converted in part into AMP by action of the enzyme myokinase (adenylate kinase), which catalyzes the reaction
|
| AMP activates both the basal and phosphorylated forms of phosphorylase, enhancing glycogenolysis either in the absence or presence of hormonal stimulation. AMP also relieves inhibition of phosphofructokinase-1 (PFK-1) by ATP (see Chapter 11), stimulating the utilization of glucose through glycolysis for energy production. The stimulatory effects of Ca2+ and AMP assure that the muscle can respond to its energy needs, even in the absence of hormonal input.
|
|
