Adenylate cyclase hormones affecting

Other oncogenes code for proteins that bind guanine nucleotides, and others code for nuclear proteins. The guanine nucleotide-binding proteins, the so-called G proteins, affect several key reactions. Some G proteins are stimulatory, whereas others are inhibitory. For example, they link hormone receptors to adenylate cyclase, they translocate... 

The cAMP system also derives some of its specificity from the proteins that are substrates for cAMP-dependent protein kinase. It is an indirect regulatory system, since cAMP modulates the activity of cAMP-dependent protein kinase and the kinase, in turn, affects the activities of a variety of metabolic enzymes or other proteins. This indirectness is the basis for amplification of the hormonal signal. Activation of adenylate cyclase by binding of a hormone molecule to a receptor causes formation of many molecules of cAMP and allows activation of many molecules of the protein kinase, each of which in turn can phosphorylate many enzymes or other proteins. This amplification cascade accounts in part for the extreme sensitivity of metabolic responses to small changes in hormone concentrations. Finally, the response to increased cAMP concentrations within a cell usually involves several metabolic pathways and a variety of enzymes or other proteins. 

Intracellular ionized calcium acts as a second messenger, coupling the action of a hormone or electrical impulse (the first messenger) on the outside of the cell to intracellular events, such as hormone or protein secretion, protein kinase activity, or muscle contraction. The effect of Ca on intracellular processes is often mediated by a small calcium-binding protein, such as troponin C in muscle (Chapter 21) or calmodulin in many other cells (Chapters 15 and 30). Synthesis of these calciumbinding proteins is not directly affected by vitamin D or any of its metabolites. Many stimuli that affect permeability to calcium also activate membrane-bound adenylate cyclase and increase the intracellular concentration of cAMP (Chapter 30). 

Lithium is one of the group lA alkali metals (like potassium and sodium) and is not normally present in the body. It acts predominantly through the phosphatidylinositol (PI) second messenger system, causing alterations in calcium- and protein kinase C (PKC)-mediated processes. Lithium can also alter the adenylate cyclase (AC) system, but this action is probably related to its toxic effects. Many calcium-dependent systems may be affected by lithium, among them regulation of receptor sensitivity, parathyroid hormone release, and proper functioning of intracellular microtubule structures. - ... 

Am. The hormones epinephrine and glucagon cannot penetrate cell membranes. They affect metabolic processes by binding to specific receptors on the membrane, which receptors in turn activate a specific enzyme bound to the inner membrane surface, adenylate cyclase. This enzyme converts ATP to cyclic AMP (cyclic adenosine monophosphate), or c-AMP. The presence of c-AMP activates another enzyme, protein kinase, which phosphorylates and activates phosphorylase kinase. Phosphorylase kinase phosphorylates phosphorylase b (inactive) to form phosphorylase a (active) which in turn cleaves glucose from glycogen by phosphorolysis to yield glucose-I-PO4. 

The adenylate cyclase reaction is rapid, and the increased concentration of intracellular cAMP is short-hved, since it is rapidly hydrolyzed and destroyed by the enzyme cAMP phosphodiesterase, which terminates the hormonal response. The continual and rapid removal of cAMP and free calcium ions from the cytosol makes for both the rapid increase and decrease of these intracellular mediators when the cells respond to signals. Rising cAMP concentrations affect cells by stimulating cAMP-dependent protein kinases to phosphorylate-specific target proteins. 

The only other 3, 5 -cyclic nucleotide found in nature to date is cyclic GMP. Like cyclic AMP, the guanine derivative is excreted in the urine in relatively large amounts. The amount of cyclic GMP excreted in rat urine docs vary with the endocrine status of the animal, but specific hormones affect it differently than cyclic AMP. Cyclic GMP is widely distributed in nature, but is present in tissues in lower concentrations than cyclic AMP. Its synthesis is catalyzed by a cyclase distinct from adenyl cyclase. 

---