Regulated diacylglycerol metabolism

In 1953, Hokin and Hokin reported that the application of acetylcholine to pigeon pancreatic tissue slices resulted in a rapid incorporation of radioactive [32p]orthophosphate into membrane phosphoinositides and phosphatidic acid (Hokin and Hokin, 1953). From these observations they hypothesized that the effect of acetylcholine was due to the rapid degradation and resynthesis 

Diacylglycerol derived from the hydrolysis of phosphoinositides by phosphoinositide-specific phospholipase C 

DAG formed from the hydrolysis of phosphoinositides first appears in the membrane within seconds of receptor occupancy, but levels drop rapidly thereafter and basal levels are restored within 1-2 ninutes (Hughes et al, 1984 Wright et al, 1988 Cook et al, 1990 Nishizuka, 1992). The duration of DAG signaling is determined by the availability of phosphatidylinositol-4,5-bisphosphate in the cell, which typically represents less than 1% of the mass of aU phosphohpids, and by rapid metabolic clearance of DAG by DAG kinases and hydrolases which serve to terminate the signal. 

Many of the extracellular hgands that stimulate the PI-PLC system will also activate other Upases. This was first recognized in 1985, when it was noted that 

---

Fig. 1. A model for the pleiotropic effects of LH on functions of Leydig cells. LH interacts with its specific receptor in the plasma membrane of the Leydig cell which results in the activation of several transducing systems and the formation of several second messengers (cyclic AMP, Ca2+, diacylglycerol and arachidonic acid metabolites). Protein kinases (A, C and calmodulin dependent) are activated resulting in the phosphorylation of specific proteins and the synthesis of specific proteins. The (phospho)proteins are involved in the transport of cholesterol to, and the control of, cholesterol metabolism in the inner mitochondrial membrane. Arachidonic acid metabolites (prostaglandins, leukotrienes) may also control steroidogenesis. LH can also regulate the secretion of proteins. The trophic effects of LH are manifested in the growth and differentiation of the Leydig cells.

Phosphatidylinositol, containing the optically inactive form of inositol - myoinositol, is a common constituent of animal, plant and microbial lipids. Often in animal tissues. It Is accompanied by small amounts of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-blsphosphate (polyphosphoinositides). These compounds have a rapid rate of metabolism in animal cells, and with their diacylglycerol metabolites have a major role in regulating vital processes. The topic has been reviewed [388],... 

This phenomenon is a recently discovered form of metabolic control and enzymes that exist in different locations in the cell and can regulate metabolism by moving from one location to another are called ambiquitous enzymes. Another example in lipid metabolism is the CTP phosphoryl-choline cytidylyl transferase which regulates the biosynthesis of phosphatidylcholine (7.1.4). The diacylglycerols formed by the action of PAP... 

---