BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 14. LIPID METABOLISM

14.6. Metabolism of Phosphoacylglycerols

Like other Structural components of Biomembranes, Phospholipids undergo constant turnover, maintaining a state of dynamic equilibrium between Synthesis and Catabolism. Phospholipids are intensively renewed in highly active tissues such as the Liver, Nervous Tissue, and both endocrine and exocrine glands.

The precursors of phosphoacylglycerols, similar to triacylglycerols, are glycerol-3-phosphate and fatty acyl-CoA esters, and The pathway of their formation shares several initial steps catalyzed by the same Enzymes (Fig. 14.9, reactions 1-2):

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Fig. 14.9. Scheme of phosphoacylglycerol Biosynthesis

In animal Cells, there are several pathways for The formation of phosphoacylglycerols. The primary ones are de novo synthesis and the Choline salvage pathway.

De novo synthesis, also known as the cytidine pathway, proceeds with the participation of cytidine Coenzymes (Fig. 14.9, reactions 3-6). Initially, a reaction between phosphatidate and cytidine triphosphate (CTP) yields CDP-diacylglycerol, which subsequently reacts with the hydroxyl group of an amino alcohol (choline, ethanolamine) or an amino acid (Serine, Threonine) to form phosphoacylglycerols:

It should be noted that cytidine NUCLEOTIDES fulfill a function in this synthesis analogous to that of uridine nucleotides in Glycogen synthesis. In both cases, activated intermediate metabolites are formed: UDP-glucose and CDP-diacylglycerol.

Decarboxylation of the serine residue in the phosphatidylserine molecule yields phosphatidylethanolamine. Phosphatidylcholine is synthesized by the methylation of the ethanolamine residue—which is part of phosphatidylethanolamine—utilizing three molecules of S-adenosylmethionine (SAM), a universal methyl group donor:

Other membrane phospholipids—phosphatidylglycerides, cardiolipins, and phosphoinositides—are also synthesized via CDP-diacylglycerol (Fig. 14.9, reactions 7-11). First, the reaction of CDP-diacylglycerol with glycerol-3-phosphate produces phosphatidylglycerol phosphate, which is subsequently dephosphorylated and converted into phosphatidylglycerol:

The interaction of phosphatidylglycerol with CDP-diacylglycerol synthesizes cardiolipins, which are the major phospholipids of mitochondrial membranes:

During The biosynthesis of phosphoinositides, the phosphatidyl residue from the CDP-diacylglycerol molecule is transferred to Inositol to form monophosphoinositol:

Monophosphoinositides are converted into di- and polyphosphoinositides through the phosphorylation of free inositol hydroxyl groups mediated by ATP.

Another pathway of phosphoacylglycerol synthesis (Fig. 14.9, reactions 12-15) utilizes 1,2-diacylglycerol as a precursor substrate, to which an activated phosphoethanolamine is attached. The latter is previously activated by ethanolamine kinase in the presence of two nucleoside triphosphates—ATP and CTP:

In the subsequent reaction, the phosphocholine residue of CDP-choline is transferred to 1,2-diacylglycerol, resulting in the formation of phosphatidylcholine.

In animals with a limited capacity for de novo lecithin synthesis due to Methionine deficiency in their standard diet, the choline salvage pathway is truly life-saving. Choline supplied to these animals through food can thus be considered a conditional vitamin.

The breakdown of phosphoacylglycerols proceeds via a hydrolytic pathway involving phospholipase acylhydrolases (see Fig. 14.2).

Pancreatic phospholipases and enzymes from other tissues are characterized by positional and stereospecificity toward the bonds they hydrolyze. They exhibit high substrate Specificity for various groups of phospholipids (such as phospholipase C). The activity of certain phospholipases (phospholipases A2 and D) is regulated by Ca²⁺ ions.

Phosphatidylcholine is synthesized in animal tissues in a similar manner. The alternative pathway of phosphatidylcholine biosynthesis is referred to as the reutilization or salvage pathway (Fig. 14.9, reactions 16-18). In this pathway, choline released during the breakdown of phosphatidylcholine and other choline-containing compounds is phosphorylated by choline kinase with the participation of ATP to form phosphocholine, which then reacts with CTP to yield the activated choline derivative, CDP-choline: