Role of Phospholipids | Biochemistry

In this article we will discuss about the role of phospholipids.

Biological membranes are mainly formed by proteins and lipids. In the latter group of constituents, phosphatides and cholesterol are the quantitative­ly dominant substances.

The physical state of phosphatides varies with the temperature. Between the true liquid state and the solid state, these lipids pass through states in which they have a more or less fluid consistency. Thus, by heating certain phos­phatides, one will have successively: “solid” state (phase) → “gel” state → “liquid crystal” state → “liquid” state.

The passage from one state to the other is called: phase transition. Numerous factors influence the temperature at which transition from one phase to the other takes place: nature of the polar part of the phosphatide, water content, presence or absence of ions etc.

However, one of the factors which appears to predominate is the nature of fatty acids present in the molecule. Although there is no close correlation between transition temperatures and melting points of fatty acids, one can well understand that a phosphatide with two stearic acids, will have transition temperatures much higher than the same phosphatide having 2 arachidonic acids.

In almost all the biological membranes studied, the arrangement of fatty acids in the phosphatides (presence of a saturated fatty acid and an unsaturated fatty acid) is such that the latter are, at the “biological” temperatures (between 20 and 40°), in a gel or “liquid crystal” state which represents a more or less fluid state.

It would appear, at least in mammals, that the phosphatides of a particular composition in fatty acids could play a special role (for example, like some molecules of phosphatidyl-choline of the lung which have both their fatty acids saturated and which play a role of surface active lipids).

Cholesterol serves as a “buffer”. It “stabilizes” the biological membranes in a fluid state. It acts by fluidizing the structure which are too rigid (for example, myelin which would “crystallize” in absence of cholesterol) or by rigidifying those excessively fluid.

Studies, using numerous physical techniques, have shown that biological membranes have the same phase transitions as the lipids they contain. On measuring the gel—”liquid crystal” transition temperature, it is observed that it is similar for the membrane and the lipids isolated from this membrane. It may therefore be concluded that the membrane lipids are the main agents responsible for the physical state of the membrane.

This physical state is of great importance in certain phenomena. Membranes are permeability barriers. One may well imagine that the movement of numerous molecules which must cross the membrane (whatever the mechanism permitting this passage) will be more or less easy depending on the degree of fluidity of the membrane. Similarly, certain enzymes change their conformation during their action on a substrate. An excessively rigid environment can inhibit this change in conformation and therefore inhibit enzymatic activity.

Numerous organisms, especially the unicellular ones, are capable of growing at very different temperatures (e.g., 10 to 40°). These organisms possess systems which can adjust the fluidity of their lipids, i.e. of their membrane, according to the temperature.

In particular, the activity of enzymes which unsaturate the fatty acids is very sensitive to temperature. The same is true of the enzymes responsible for the incorporation of fatty acids in phosphatidic acids and therefore in phosphatides. Variations can thus exist in the structure of phosphatides incorporated in the membranes; this maintains the fluidity compatible with proper cellular functioning.

Anchoring of (Glyco) Proteins:

One of the modes of anchoring of (glyco) proteins in cellular plasmatic membranes takes place thanks to a phosphatide: phosphatidyl inositol. The structure of the anchoring complex would be: phosphatidyl inositol— (ethanolamine-monosaccharides)—protein, the diacyl-glycerol of the phos­phatide being inserted in the membrane.

Several proteins (acetylcholinesterase, 5′ nucleotidase for example in mam­mals and also a surface glycoprotein in Trypanosoma brucei, a proteinase of Leishmania major,…) are attached to the membrane in this manner.

Simpler anchoring systems are also known. A fatty acid (generally, myristic acid) is linked by an amide group to an α-amino group of the N-terminal residue. This is the case for example, of NADH: cytochrome b₅ reductase or several viral proteins.

If the N-terminal residue of protein is cysteine, it is linked by amide linkage with palmitic acid as previously, but in addition by thioether linkage with a diacylglycerol. This is the case of the penicillinase of the Bacillus or the receptor of transferrin for example.

Cycle of Inositol Triphosphate:

The binding to the membrane receptor of some compounds including neurotransmitter (acetylcholine, adrenaline, dopamine), hormones (vasopres­sin…), mitogens (growth factors), as well as various other compounds like thrombin (protease) or the platelet activation factor (PAF), leads to the activa­tion of a phospholipase C which specifically hydrolyzes phosphatidyl-inositol diphosphate (Phyl IP2) to diglycerides and inositol triphosphate (IP3).

The diglycerides formed can activate a protein kinase (kinase C). Inositol triphos­phate brings about the mobilization of intracellular calcium and induces the activation of Ca⁺⁺ —dependent enzymes, particularly those with their activity modulated by calmoduline, an activator protein sequestering calcium. These phenomena are very rapid.

IP3 is inactivated by phosphatases which hydrolyse it to inositol. Phosphatidyl-inositol diphosphate is resynthesized from inositol and glycerides or phosphatidic acid (see diagram). In view of its role, inositol triphosphate is considered to be a secondary mediator.

In some cases, the diglyceride formed, instead of activating a kinase C, will be hydrolyzed by a phospholipase A with liberation of arachidonic acid which can either be transformed into prostaglandines, or directly activate adenylate cyclase with formation of cyclic AMP. This cycle of inositol is also present in plants, but its exact role is not yet known. Light would be one of the activators. As in mammals, the liberated IP₃ is a mobilizing agent of the intracellular Ca⁺⁺.

A simpler cycle exists in cells of mammals. Stimulation by compounds like the Epidermal Growth Factor (EGF), a growth factor, activates a phospholipase C which hydrolyzes phosphatidylcholine with liberation of diglyceride which will activate a kinase C.