Hydrolase phosphatidic acid phospho

The activity of PLD on phosphatidylcholine generates phosphatidic acid, and this may be further metabolised by the enzyme phosphatidate phospho-hydrolase to form DAG (Fig. 6.19). Furthermore, the activity of DAG kinase can convert the DAG (generated either from phosphatidic acid or from the activity of PLC) back into phosphatidic acid. Both phosphatidic acid and DAG have functions as second messengers thus the activities of PLD, phosphatidate phosphohydrolase and DAG kinase all play important roles in the generation of these intracellular signalling molecules. 

Figure 6.19. Products of phosphatidylcholine metabolism. Phosphatidylcholine is metabolised to phosphatidic acid via the activity of phospholipase D. The phosphatidic acid generated in this way may then be converted into diacylglycerol via phosphatidate phospho-hydrolase (which is inhibited by propranolol), and the enzyme diacylglycerol kinase may regenerate the phosphatidic acid. Phospholipase D may also catalyse the transphosphati-dylation of primary alcohols, such as ethanol and butanol, at the expense of the natural substrate, phosphatidylcholine. Thus, primary alcohols can prevent phosphatidic acid production via this route.

Fig. 1. Targeted lipidomics of anandamide metabolism. Postulated pathways of anandamide metabolism. Abbreviations PC, phosphatidylcholine PE, phosphatidylethanolamine NAT, JV-acyl transferase LPA, lysophosphatidic acid PA, phosphatidic acid NAPE, jV-acyl-phosphatidylethanolamine Lyso-NAPE, l-lyso,2-acyl-OT-glycero-3-phosphoethanolamine-JV-acyl ABHD-4, a//3 hydrolase-4 GP-anandamide, glycerophospho-anandamide PAEA, phospho-anandamide PLA, phospholipase A NAPE-PLD, NAPE phospholipase D PLC, phospholipase C FAAH, fatty acid amide hydrolase P, phosphatase COX, cyclooxygenase LOX, lipoxygenase CYP450, cytochrome P450 PDE, phosphodiesterase.

In the biosynthesis of many of the glycerophosphatides, phosphatidic acid is first dephosphorylated. Smith, Weiss and Kennedy (1957) showed that liver contains an enzyme, phosphatidic acid phosphatase (L-a-phosphatidate phospho-hydrolase EC 3.1.3.4), which removes phosphate from phosphatidic acid with the formation of D-a, j8-diglyceride (II) ... 

The incorporation of [ H]-water into synthesized diacylglycerols was reduced even more than the incorporation into the other two lipid classes. As the sulfur-substituted fatty acids had only small effects on incorporation of pH]-water into cell monoacylgjyc-erols (data not shown), these data suggest that 3-thia fatty acids decreased TG-synfliesis by affecting the step before formation of diacylglycerols. The reduced incorporation into diacylglycerols, thus, may indicate that activity of the enzyme phosphatidate phospho-hydrolase could be affected. 

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