THE ANIMAL PHOSPHOLIPIDS: THEIR STRUCTURE, METABOLISM and BIOLOGICAL SIGNIFICANCE

Abstract

SUMMARY Phospholipids are universally present in all mammalian tissues and in all parts of the cell, including the mitochondria, microsomes and nucleus. They appear often to be attached to the tissue proteins by some unknown type of bonding. The use of physical methods of fractionation to separate crude lipids extracted from tissues has resulted in the discovery of a number of new phospholipids apart from lecithin, cephalin and sphingomyelin, notably phosphatidylserine, phosphatidylinositol and diphosphoinositide. As isolated, the phosphoglycerides all have the a structure and the L configuration. Evidence is accumulating that individual animal tissues can synthesize their complete requirements of new phospholipids without resource to other organs. In all tissues, even in the adult animal, the phospholipids are continually being broken down and resynthesized at the same rate, so that under normal physiological conditions a constant concentration is maintained. The mechanism of phospholipid biosynthesis has only been ascertained up to now for the phosphoglycerides: lecithin and phosphatidylethanolamine. With these compounds a phosphorylated base molecule (phosphorylcholine or phosphoryl‐ethanolamine) first reacts with cytidine triphosphate, forming an activated complex, cytidine diphosphate ‘base’. This then combines with a diglyceride molecule, forming the phosphoglyceride, and splitting off cytidine monophosphate. It is possible that the diglyceride needed by the system is formed by the dephosphoryla‐tion of phosphatidic acid, a lipid which is enzymically synthesized in tissues from α‐glycerophosphoric acid and two coenzyme A‐activated fatty acids. One route for the catabolism of lecithin and phosphatidylethanolamine appears to be through the lysophosphoglycerides and glycerophosphorylated bases. The glycerophosphate finally formed can either be used for phosphoglyceride resynthesis or it can enter the glycolytic system of the tissue. Certain isotopic evidence suggests that, as well as this catabolic process, the phosphorylated base ‘units’ may turnover independently and more rapidly than the glyceride part of the phospholipid molecule. Possibly the recent and unconfirmed demonstration of a phospholipase C, which forms phosphorylcholine from lecithin, may be connected with this process. The rate at which individual phospholipids turnover in various organs has still to be ascertained. Many previous estimates are unsatisfactory because inadequate experimental results have been applied to theoretically derived formulae expressing turnover rates. For similar reasons it is often extremely difficult to interpret reported changes in the incorporation rate of isotopes into phospholipids during physiological activity. No definite metabolic role can yet be ascribed to phospholipids which would account for their rapid turnover in tissues. The evidence is against their being obligatory intermediates, either in the resynthesis of triglycerides during fat digestion or in the oxidation of neutral fat. Neither do they appear ...

Hypercephalinemia and Experimental Venous Thrombosis in the Rat

“…I n the present study a shortening of the recalcification time of plasma was noted after intraperitoneal injection of cephalin suspension prepared from rat brain. The accelerated clotting activity persisted for hours, which may indicate a slow absorption from the peritoneal cavity as well as a slow turnover time of the cephalins in plasma (Dawson 1957).…”

The mast cells

“…A preliminary investigation has therefore been started in co-operation with Dr. R. M. C. Dawson of Cambridge who has made a detailed study of the phosphatidic acids and their identification in biological material. Various tissues, rich in mast cells, have been sent to Dr. Dawson, either in 1 : 1 chloroform/methanol or after preliminary hydrolysis, and he has chromatographed them against known standards (Dawson, 1957). A special effort was made to obtain a reasonably pure sample of isolated mast-cell granules from the rat by taking advantage of the fact that the granules in this species are remarkably resistant to the lytic action of water (Paff and Mergenthaler, 1955).…”

The Effect of X-Rays on Lipids, Phospholipids and Cholesterol of the Mouse Testis

“…The proportionate increase of phospholipids in the present study occurs as soon as regeneration of the tubules starts, showing that this might be due to a resurgence of spermatogenesis. Dawson (1957) claims that 'this type of synthesis may vary considerably and its rate may be in excess of that required for the normal turnover of structural elements'. There is certainly a marked increase in the vascularization of the testis once regeneration occurs (Kochar & Harrison, 1971b).…”