Protein kinase triacylglycerol, adipose tissue

Triacylglycerol lipase from adipose tissue is directly activated by a cyclic AMP-dependent protein kinase [92]. Adipose tissue lipase is also activated by skeletal muscle cyclic AMP-dependent protein kinase [93]. 

When certain hormones (e.g., epinephrine) bind to their receptors in adipose tissue, adenylate cyclase is activated. The cAMP that is formed activates protein kinase A, which phosphorylates triacylglycerol lipase. The phosphorylated form of this enzyme is the active species, and triacylglycerols are degraded to fatty acids. 

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. 

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. 

The initial event in the utilization of fat as an energy source is the hydrolysis of triacylglycerols by lipases, an event referred to as lipolysis. The lipase of adipose tissue are activated on treatment of these cells with the hormones epinephrine, norepinephrine, glucagon, and adrenocorticotropic hormone. In adipose cells, these hormones trigger 7TM receptors that activate adenylate cyclase (Section 15,1.3 ). The increased level of cyclic AMP then stimulates protein kinase A, -which activates the lipases by phosphorylating them. Thus, epinephrine, norepinephrine, glucagon, and adrenocorticotropic hormone induce lipolysis (Figure 22.6). In contrast, insulin inhibits lipolysis. The released fatty acids are not soluble in blood plasma, and so, on release, serum albumin binds the fatty acids and serves as a carrier. By these means, free fatty acids are made accessible as a fuel in other tissues. 

When certain hormones bind to their receptors in adipose tissue, a cascade mechanism releases fatty acids and glycerol from triacylglycerol molecules. Triacylglycerol lipase (sometimes referred to as hormone-sensitive lipase) is activated when it is phosphorylated by protein kinase. Protein kinase is activated by cAMP. After their transport across the plasma membrane, fatty acids are transported in blood to other organs bound to serum albumen. 

Insulin causes activation of a protein tyrosine kinase in many cells. Insulin also causes increased glucose transport in selected tissues. Insulin will stimulate dephosphorylation of many proteins phosphorylated in response to cAMP. Insulin is an anabolic hormone and in many tissues causes increases in protein and glycogen synthesis. Insulin also causes an increase in adipose lipoprotein lipase and triacylglycerol storage in the adipose tissue. 

Fig. 36.10. Regulation of hormone-sensitive hpase (HSL) in adipose tissue. During fasting, the glucagon/insuhn ratio rises, causing cAMP levels to be elevated. Protein kinase A is activated and phosphorylates HSL, activating this enzyme. HSL-P initiates the mobilization of adipose triacylglycerol by removing a fatly acid (FA). Other lipases then act, producing fatty acids and glycerol. Insulin stimulates the phosphatase that inactivates HSL in the fed state.

---