CAMP-dependent triacylglycerol

Norepinephrine secreted at sympathetic nerve endings binds to y8-adrenergic receptors on brown adipose tissue cells and initiates cAMP-dependent triacylglycerol lipase... 

Increased lipid synthesis/inhibi-tion of lipolysis Activation of lipoprotein lipase (LPL)/induc-tion of fatty acid synthase (FAS)/inactivation of hormone sensitive lipase (HSL) Facilitated uptake of fatty acids by LPL-dependent hydrolysis of triacylglycerol from circulating lipoproteins. Increased lipid synthesis through Akt-mediated FAS-expression. Inhibition of lipolysis by preventing cAMP-dependent activation of HSL (insulin-dependent activation of phosphodiesterases )... 

Fatty acids are carried to tissues for use in synthesis of triacylglycerols, phospholipids, and other membrane lipids. The mobilization of fatty acids from triacylglycerol stores and from cholesterol esters depends upon hormone-sensitive lipase (p. 635).53b/ 53c This enzyme is activated by cAMP-dependent phos-... 

Variability in hormonal response patterns does not stop at the level of second-messenger synthesis. Thus, cyclic AMP can activate the well-known cAMP-dependent protein kinase A, but the possibility of other cAMP-respon-sive enzymes or cAMP-activated regulatory proteins should not be ruled out. The protein kinase activated by cAMP can activate a number of other enzymes. For example, in the liver, phosphorylase kinase (see fig. 24.15) is activated and catalyzes the breakdown of glycogen. In adipocytes, triacyl-glycerol lipase is activated and catalyzes the breakdown of triacylglycerols. 

Regulation The concentration of free fatty acids in the blood is controlled by the rate at which hormone-sensitive triacylglycerol lipase hydrolyzes the triacylglycerols stored in adipose tissue. Glucagon, epinephrine and norepinephrine cause an increase in the intracellular level of cAMP which allosterically activates cAMP-dependent protein kinase. The kinase in turn phosphorylates hormone-sensitive lipase, activating it, and leading to the release of fatty acids into the blood. Insulin has the opposite effect it decreases the level of cAMP which leads to the dephosphorylation and inactivation of hormone-sensitive lipase. 

In response to energy demands, the fatty acids of stored triacylglycerols must be mobilised for use by peripheral tissues. This release is controUed by a complex series of interrelated cascades that result in the activation of hormone-sensitive lipase. In adipocytes this stimulus can come from glucagon, adrenaline (epinephrine) or 8-corticotropin. These hormones bind cell-surface receptors that are coupled to the activation of adenyl cyclase the resultant increase in intracellular cAMP leads to activation of cAMP-dependent protein kinase, which in turn phosphorylates and activates hormone-sensitive lipase (Figure 5.5). 

Synthesis of phosphatidylcholine. The rate-limiting reaction is that catalyzed by cytidylyltransferase (reaction 2) which appears to be active only when attached to the endoplasmic reticulum, although it is also found free in the cytosol. Cytidylyltransferase is inactivated by a cAMP-dependent protein kinase and activated by a phosphatase. Translocation to the endoplasmic reticulum can be stimulated by substrates such as fatty acyl Coenzyme A (CoA). Choline deficiency can result in deposition of triacylglycerol in liver and reduced phospholipid synthesis. Enzymes (1) choline kinase ... 

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