In this article we will discuss about:- 1. Distribution of Phospholipids 2. Classification of Phospholipids 3. Synthesis 4. Functions 5. Role of Endocrines.
Distribution of Phospholipids:
The salient facts about the distribution of phospholipids are summarized below:
i. The phospholipids are widely distributed in the body and are contained within it. They remain in the cell membrane as well as in the protoplasm. They enter into the structure of the cells and form the composition of the element constant of the cells.
ii. Brain and nervous tissues contain the maximum amount of all the three varieties, i.e., lecithin, cephalin and sphingomyelin. Sphingomyelin is present chiefly in the nervous tissue and negligible amount in other tissues. But lecithin and cephalin are found in considerable amounts in other tissues.
iii. The phospholipid content of a particular organ or tissue, in a given species of animal, is constant both in composition and in amount.
iv. The fatty acids in the phospholipids molecule are more unsaturated than those in the neutral fat. The degree of unsaturation seems to be more or less characteristic of a particular tissue, because the iodine value of the phosphatides of a particular tissue is of the same order.
v. Phospholipids always remain along with cholesterol. The rise or fall of one is always accompanied by a similar change in the other.
Classification of Phospholipids:
Phospholipids belong to the group of conjugated fats, containing sugar alcohol or complex amino alcohol, fatty acid, phosphoric acid and nitrogenous base.
They may be classified as follows:
In these compounds there are 1 molecule of phosphoric acid, 2 molecules of fatty acids, 1 molecule of glycerol and 1 molecule of nitrogenous base (choline or ethanolamine). The examples are lecithin and kephalin or cephalin.
In these compounds there are 1 molecule of phosphoric acid and 2 molecules of nitrogenous bases, viz., sphingosine and choline; for example, sphingomyelin.
Synthesis of Phospholipids:
The human body can synthesise phospholipids under suitable conditions provided all other constituents are available.
The evidence is as follows:
i. Liver can easily synthesise phospholipids. As a matter of fact large amounts of phospholipids are daily synthesized by the liver from the intermediate products of fat oxidation.
ii. The lipotropic action (reduction of fat content) of choline on liver is due to the fact that choline helps in converting neutral fat into phospholipids (lecithin). In this form the fat becomes highly diffusible, easily passes out of liver and thus the liver fat is reduced. It is indicated that the phospholipids are normally synthesised in the liver.
iii. Phospholipids are also synthesized inside the intestinal epithelium during the absorption of fat.
iv. The fact that all tissues contain a constant amount of phospholipids, having a characteristic composition which indicates that the cells of the different tissues can, at least to some extent, synthesise their own phospholipids locally.
Synthesis of Lecithin (Phosphatidyl Choline):
In the first step phosphate ester of choline (phosphoryl choline) is formed out of choline and ATP. Phosphoryl choline then reacts with cytidine triphosphate (CTP) forming cytidine diphosphate (CDP) choline and inorganic pyrophosphate (PPi). Then a diglyceride combines with the phosphoryl choline part of cytidine diphosphate choline to form lecithin (phosphatidyl choline) and cytidine monophosphate (CMP), the latter is rephosphorylated by ATP and thus reconverted to CTP.
Diglycerides are formed from the glycerol in the liver, intestine and adipose tissue. The glycerol may be absorbed in the intestine as such or formed in the body from fructose-1-6 diphosphate. The first step in the synthesis of diglycerides from glycerol is the action of enzyme glycerol kinase on ATP and glycerol with the formation of L-α-glycerophosphate.
The L-α-glycerophosphate is also formed from fructose-1-6-diphosphate. The L-α-glycerophosphate reacts with acyl CoA in presence of an enzyme to form the phosphatidic acid. The phosphatidic acid is then hydrolysed by phosphatase with the formation of D-1-2-diglyceride (Fig. 10.25).
Reaction for the synthesis of cephalin is mostly analogous to those for the synthesis of lecithin. The serine may be formed from glycine or may come from the dietary source (Fig. 10.26).
The sphingomyelin contains fatty acids, phosphoric acid, choline and a complex amino alcohol sphingol or sphingosine. The synthesis of sphingosine has been studied in brain tissue. The first step in the synthesis of sphingosine is the reduction of palmityl CoA to the palmityl aldehyde.
The palmityl aldehyde on condensation with serine in presence of pyridoxal phosphate gives rise to dihydrosphingosine. Sphingosine is formed after oxidation of dihydrosphingosine. In vivo the sphingomyelin is synthesised from sphingosine phosphoryl choline. Detailed pathways are shown in Fig. 10.27.
Functions of Phospholipids:
i. Essential Constituent of all Cells:
In the form of element constant phospholipids constitute an essential part of cell protoplasm.
ii. Relation with Cell Function:
It has been shown that the phospholipid content of an organ varies in direct proportion to the degree of its activity. From this fact it has been suggested that the phospholipid content of a tissue is intimately related to cell function and may be regarded as an index of the degree of activity of that tissue.
iii. Fat Digestion and Transport:
The lecithin contents of bile and food are concerned for the emulsifying action of bile salts upon food fats, and thus help their digestion. Lecithin is an important form in which fat is transported in considerable amount into blood. As phospholipids easily form emulsion with H2O, so transport of fat from cell to cell takes place in the form of phospholipids.
iv. Protection and Permeability of Cells:
Being a constant constituent of cell membrane, phospholipids exert a protective action upon the cells and also regulate the passage of various substances across the cell membrane.
v. Relation with Tissue Oxidation:
It has been suggested that the phospholipids being highly unsaturated compounds may act as oxygen carriers in the cell and help in tissue oxidation. Oxygen may be taken up at the unsaturated bonds and under a suitable condition it is released while required for oxidation purposes. They play a major role in regulating the respiratory group of enzymes, cytochrome complex.
vi. Relation with Blood Clotting:
Phospholipid has a major role in the reaction sequence leading to the formation of blood clot. It has also been noted that rise in blood phospholipid concentration causes depression of fibrinolytic mechanism and reduces the tissue-activating factor VIII concerned for coagulation and stimulates the synthesis of prothrombinase.
vii. Donors of Phosphate Group:
Phospholipids donate phosphate group for various reactions in the body.
viii. ‘Carriers’ in Active Transport:
It has been suggested that phospholipids act as ‘carriers’ for the transport of substances, e.g., hormones, enzymes, mucins, etc., through cell membrane.
Cerebrosides, found in brain, adrenal glands, liver, kidney, etc., are glycolipids, e.g., sphingomyelin composed of ceramide (sphingosine) and phosphocholine derived from CDP-choline. In a condition known as Gaucher’s disease, an increase in cerebroside content has been observed in spleen, liver and lymph nodes. Gangliosides and sulphatides are formed from cerebrosides.
Gangliosides contain neuraminic acid in addition. In Tay-Sachs disease this lipid accumulates in ganglion cells particularly of cerebral cortex. Cerebronic acid ester of sulphuric acid occurs in sulphatides which have been found in many tissues including brain. Increased accumulation has been noted in a pathological condition, metachromatic leukodystrophy.
Role of Endocrines of Phospholipid:
i. Adrenal Cortex:
Adrenal cortex, by its probable influence on phosphorylation exerts an important effect in the synthesis and breakdown of phospholipids. The active principles of adrenal cortex are believed to help the local enzymes (phosphatase or phosphorylase) which are directly concerned with phosphate transfer. The rise of plasma phosphatides as well as the hyperactivity of the adrenal cortex, during pregnancy, may indicate that the adrenal cortex is responsible for the synthesis of phosphatides.
ii. Anterior Pituitary:
It is possible that the ultimate control of phosphorylation is carried out be anterior pituitary which regulates the activity of adrenal cortex through its adrenocorticotrophic hormone (ACTH).
Insulin decreases the phospholipid content of plasma.
Repeated injection of thyroxin increases the phospholipid content of liver. Removal of thyroid decreases it.