Phosphorylation adenyl cyclase regulation

Vanadium. Vanadium is essential in rats and chicks (85,156). Estimated human intake is less than 4 mg/d. In animals, deficiency results in impaired growth, reproduction, and Hpid metaboHsm (157), and altered thyroid peroxidase activities (112). The levels of coen2yme A and coen2yme Q q in rats are reduced and monoamine oxidase activity is increased when rats are given excess vanadium (157). Vanadium may play a role in the regulation of (NaK)—ATPase, phosphoryl transferases, adenylate cyclase, and protein kinases (112). 

Regulation of Adenylate Cyclase and Neurotransmitter Release - Protein Phosphorylation Mechanisms... 

The breakdown of fatty acids in (3-oxidation (see Topic K2) is controlled mainly by the concentration of free fatty acids in the blood, which is, in turn, controlled by the hydrolysis rate of triacylglycerols in adipose tissue by hormone-sensitive triacylglycerol lipase. This enzyme is regulated by phosphorylation and dephosphorylation (Fig. 5) in response to hormonally controlled levels of the intracellular second messenger cAMP (see Topic E5). The catabolic hormones glucagon, epinephrine and norepinephrine bind to receptor proteins on the cell surface and increase the levels of cAMP in adipose cells through activation of adenylate cyclase (see Topic E5). The cAMP allosterically activates... 

The release of fatty acids from adipose tissue is regulated by the rate of hydrolysis of triacylglycerol and the rate of esterification of acyl-CoA with glycerol 3-phosphate. The rate of hydrolysis is stimulated by hormones that bind to cell-surface receptors and stimulate adenylate cyclase (which catalyzes the production of cAMP from ATP). Hormone-sensitive lipase (Sec. 13.4) can exist in two forms, one of which exhibits very low activity and a second which is phosphorylated and has high activity. Before hormonal stimulation of adenylate cyclase, the low-activity lipase predominates in the fat cell. Stimulation of protein kinase by an increase in cAMP concentration leads to phosphorylation of the low-activity lipase. An increase in the rate of hydrolysis of triacylglycerol and the release of fatty acids from the fat cell follows. This leads to a greater utilization of fatty acids by tissues such as heart, skeletal muscle, and liver. 

Figure 8 Simplified diagram of a signaling cascade that involves NE, BDNF, and CREB after NE acts on the postsynaptic fi-noradrenergic receptor. NE couples to a G protein (Gas), which stimulates the production of cAMP from adenosine triphosphate (ATP). This reaction is catalyzed by adenylate cyclase (AC). cAMP activates protein kinase A (PKA). Inside the cell, PKA phosphorylates (P) the CREB protein, which binds upstream from specific regions of genes and regulates their expression. BDNF is one target of cAMP signaling pathways in the brain. CRE, cyclic AMP regulatory element ER, endoplasmic reticulum, [reprinted from Reference 76 with permission of the author and the publisher, Canadian Medical Association].

Fig. 20. Hypothetical model of how insulin secretion is regulated. The most important event is the depolarization of the B-cell which causes Ca"+ influx along L-type Ca2+ channels and subsequent increase in cytosolic Ca"+. Depolarization is produced by nutrient (glucose) metabolism via an increase in B-cell ATP and/or ATP/ADP ratio which closes KAXP channels. Also, sulphonylureas, at a distinct location, close KATP channels. The increase in [Ca2+]j activates CaCaMK. Ca2+ uptake appears to be modulated by nutrient metabolism (redox state of NAD(P)H and GSH). Insulin release in response to depolarization is also modulated by factors affecting PLC and adenylate cyclase. Here, production of IP3 leads to release of stored Ca2+ from the endoplasmic reticiulum. DAG activates PKC whereas cAMP activates PKA. CaMK, PKC and PKA cause protein phosphorylations which finally cause granule movement and exocytosis. But there will also be other effects of phosphorylations related to stimulus-secretion coupling, e.g. a possible interaction with voltage-dependent Ca2+ channels.

TSH (also called thyrotropin), which is secreted by the pituitary, plays a central role in the regulation of growth and function of the thyroid gland. TSH receptors are functionally coupled to G-proteins thus, the extracellular stimulus by TSH is transduced into intracellular signals mediated by a number of G-proteins. Activation of Gs-protein results in the stimulation of the adenylate cyclase-cAMP-protein phosphorylation cascade. Other G-proteins coupled to TSH-receptor activation include Gg-protein, which mediates the phospholipase C-phosphatidylinositol 4,5-bisphosphate-Ca + signaling pathway (see Chapter 30 for a detailed discussion). 

The answer is b. (Murray, pp 199-207. Scriver, pp 1521-1552. Sack, pp 121-138. Wilson, pp 287-31 77) In the presence of low blood glucose, epinephrine or norepinephrine interacts with specific receptors to stimulate adenylate cyclase production of cyclic AMP Cyclic AMP activates protein kinase, which catalyzes phosphorylation and activation of phosphorylase kinase. Activated phosphorylase kinase activates glycogen phosphorylase, which catalyzes the breakdown of glycogen. Phosphorylase kinase can be activated in two ways. Phosphorylation leads to complete activation of phosphorylase kinase. Alternatively, in muscle, the transient increases in levels of Ca" associated with contraction lead to a partial activation of phosphorylase kinase. Ca" " binds to calmodulin, which is a subunit of phosphorylase kinase. Calmodulin regulates many enzymes in mammalian cells through Ca" binding. 

The answer is h. (Murray, pp 123—148. Scriver, pp 2367—2424. Sack, pp 159-175. Wilson, pp 287-317.) The regulatory enzyme of lipolysis is hormone-sensitive lipase. It is a triacylglyceride lipase of adipose cells regulated by hormones. The hormones that stimulate release of fatty acids into the blood are glucagon, epinephrine, and norepinephrine, all of which activate adipocyte membrane adenylate cyclase. This produces an increased level of cyclic AMP, which activates a protein lipase that, in turn, phosphorylates and activates the sensitive lipase. In contrast, insulin causes dephosphorylation and inhibition, thereby shutting down lipolysis and the release of fatty acids into the bloodstream. 

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