In this article we will discuss about the process of metabolism of glycerolipids, explained with the help of suitable diagrams.
Synthesis and Degradation of Glycerophospholipids:
The common precursor of all phosphatides is phosphatidic acid. There are two pathways for carrying out the biosynthesis of this lipid. In the first, glyceraldehyde-3-phosphate, which is one of the intermediates of glycolysis (see fig. 4-26) is first reduced in presence of NADH, to L-α- glycerophosphoric acid. (A specific kinase also permits, in presence of ATP, the phosphorylation of free glycerol).
Glycerophosphoric acid will react successively with two molecules of acyl-coenzyme A, in presence of an acyl transferase, to give phosphatidic acid (see fig. 5-21). The second pathway starts from dihydroxy-acetone-phosphate which reacts with an acyl-coenzyme A and gives acyl-dihydraxy-acetone-phosphate.
The ketone group is then reduced in presence of NADPH and the compound obtained will lead, after binding of a second molecule of acyl-coenzyme, to phosphatidic acid (see fig. 5-21). This second pathway permits the specific binding to glycerophosphate of saturated fatty acids in the position 1 and unsaturated fatty acids in the position 2.
The biosynthesis of non-nitrogenous phosphatides (phosphatidyl-glycerol, phosphatidyl-inositol, cardiolipid) takes place from phosphatidic acid. The latter first yields CDP-diglyceride (which may also be written CMP-P- diglyceride) after reaction with cytidine-triphosphate or CTP. Phosphatidyl- inositol (see fig. 5-21) is obtained after the transfer of the “P-diglyceride” fraction to inositol. A similar reaction gives phosphatidyl-glycerol, precursor of the cardiolipid.
The biosynthesis of nitrogenous phosphatides (phosphatidyl-choline, phos- phatidyl-ethanolamine, phosphatidyl-serine) begins with a hydrolysis of phosphatidic acid under the influence of a specific phosphatase (see fig. 5-21). The diglyceride thus formed will then react with a derivative of choline (or ethanolamine) formed as follows; choline (or ethanolamine) is first phosphory- lated by ATP under the influence of a specific kinase.
Then, the phosphorylcholine (or phosphoryl-ethanolamine) thus formed reacts with CTP (see fig. 5-20) to give cytidine-diphospho-clioline (or cytidine-diphospho-ethanolamine) called CDP-choline (or CDP-ethanolamine). Writing compounds in the form CMP-P-choline (or CMP-ethanolamine), affords a better understanding of what takes place during the reaction with the diglyceride in the formation of phosphatidyl-cholines and phosphatidyl-ethanolamines.
Indeed, the last step (see fig. 5-21) consists of a transfer, from CMP-P- choline (or CMP-P-ethanolamine), of phosphoryl-choline (or phosphoryl- ethanolamine) to the diglyceride, thus forming phosphatidyl-choline (or phosphatidyl-ethanolamine). Phosphatidyl-serine is on the contrary synthesized from phosphatidyl-ethanolamine by an exchange of the two bases.
Lastly, there is a pathway which permits the passage from phosphatidyl- ethanolamine to phosphatidyl-choline by the binding to the amino group of phosphatidyl-ethanolamine of 3 methyl groups originating from S-adenosyl- methionine (see fig. 5-21).
Phosphatidylserine is synthesized by a base exchange reaction. Phosphatidylserine can be retransformed into phosphatidyl ethanolamine by decarboxylation.
A deficiency in choline or methionine (which are not synthesized by mammalian cells) will lead to a marked decrease in the synthesis of phosphatidylcholine in the liver. As a result, the diglycerides used for the synthesis of this phosphatide are then transformed into triglycerides which accumulate (hepatic steatosis).
Phosphatidylinositol and cardiolipid (phosphatide very abundant in procaryotes) are formed from CDP diglycerides (see fig. 5-21). In bacteria, phosphatidylserine is exclusively synthesized by the reaction CDP-diglyceride + serine → CMP + phosphatidylserine. The latter is decarboxylated to phosphatidylethanolamine. A very great majority of procaryotes cannot synthesize phosphatidylcholine.
The catabolism of phosphatides is carried out by the phospholipases-phosphoesterases system described previously. Besides the lysosomial enzymes implied in the degradation of phosphatides, there are phospholipases A1 and A2 located in the other membrane fractions of the cell. These enzymes can change the nature of the fatty acids of phosphatides.
Synthesis and Degradation of Glycerides:
The diglycerides originating from the dephosphorylation of phosphatidic acid (pool different from the one used for synthesis of phosphatides) can also be acylated by a third molecule of acyl-coenzyme A, thus leading to triglycerides (see fig. 5-21). The latter are also formed by successive reaction of monoglycerides (or perhaps free glycerol) with acyl-coenzymes A, providing di- and triglycerides.
This pathway is known in insects, plants and vertebrates. In mammals, it is very secondary, except in the intestinal mucosa where it contributes to the synthesis of triglycerides from the digestion products of dietary glycerides.
Glycerides are degraded by lipases. The activity of some tissue lipases, especially in the case of adipose tissue, is very sensitive to the action of hormones like insulin (inhibitors), glucagon or adrenaline (activators), which thus regulate the degradation of glycerides stored in these tissues.