Phospholipase, hormone sensitive

A second class of serpentine receptors are coupled through a G protein to a plasma membrane phospholipase C (PLC) that is specific for the plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (see Fig. 10-15). This hormone-sensitive enzyme catalyzes the formation of two potent second messengers diacyl-glycerol and inositol 1,4,5-trisphosphate, or IP i (not to be confused with PIP3, p. 431). 

FIGURE 12-19 Hormone-activated phospholipase C and IP3. Two intracellular second messengers are produced in the hormone-sensitive phosphatidylinositol system inositol 1,4,5-trisphosphate (IP3) and diacylglycerol. Both contribute to the activation of protein kinase C. By raising cytosolic [Ca2+], IP3 also activates other Ca2+-dependent enzymes thus Ca2+ also acts as a second messenger. 

Intracellular Messengers from Phosphatidylinositols When the hormone vasopressin stimulates cleavage of phosphatidylinositol 4,5-bisphosphate by hormone-sensitive phospholipase C, two products are formed. What are they Compare their properties and their solubilities in water, and predict whether either would diffuse readily through the cytosol. 

As shown in Figure 14.6, a proportion of the phosphatidylinositol in membranes undergoes two successive phosphorylations to yield phosphatidylinositol bisphosphate. This is a substrate for hormone-sensitive phospholipase C, which is activated by the G-protein-GTP complex released into the cell membrane by a hormone receptor following binding of the hormone at the outer surface of the membrane. Phospholipase C hydrolyzes phosphatidylinositol bisphosphate to release diacylglycerol and inositol trisphosphate. 

Figure 14.6. Formation of inositol trisphosphate and diacylglycerol. Phosphatidylinos-itol kinase, EC 2.7.1.67 and hormone-sensitive phospholipase, EC 3.1.4.3.

While the coupling functions of Gs and Gj are well characterized, additional pertussis toxin-sensitive G-proteins (for example G ) have been identified whose functions are still unknown [21]. Interestingly, in certain systems pertussis-toxin treatment prevents the activation of phospholipase C both by hormones and by nonhydrolysable guanine nucleotides [21], Thus, a pertussis-toxin-sensitive G-protein other than Gj (such as Gc) may couple receptors to this transducing enzyme. In other systems activation of phospholipase C is not sensitive to pertussis toxin, indicating that if a G-protein mediates the activation of PLC in these systems, it must be via yet another member of the G-protein family. 

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