Phospholipids

Biochemistry

2nd stage
Dr.Lamees Majid Al-Janabi
PHOSPHOLIPIDS
SYNTHESIS OF THE PHOSPHOLIPIDS
There are two types of phospholipids either contain the glycerol called { glycerol phospholipids } or do not contain glycerol that called { sphingophospholipids } .
The structure of glycerol phospholipids is similar to that of the TG but on the carbon no.3 contain phosphate or phosphate alcohol.
Phospholipids are the predominant lipids of cell membranes. In membranes, the hydrophobic portion of a phospholipid molecule is associated with the nonpolar portions of other membrane constituents, such as glycolipids, proteins, and cholesterol.
Nonmembrane-bound phospholipids serve additional functions in the body, for example, as components of lung surfactant and essential components of bile, and in plasma lipoprotein particles. These Phospholipids include (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine,phosphatidylinositol, cardiolipin, plasmalogens, and sphingomyelin.

Synthesis of phosphatidylethanolamine (PE) and phosphatidylcholine (PC):

PC and PE are the most abundant phospholipids in most eukaryotic cells. The primary route of their synthesis uses choline and ethanolamine obtained either from the diet or from the turnover of the body's phospholipids.
These synthetic pathways involve the phosphorylation of choline or ethanolamine by kinases, followed by conversion to the activated form, CDP-choline or CDP-ethanolamine. Finally, choline-phosphate or ethanolamine-phosphate is transferred from the nucleotide (leaving CMP) to a molecule of diacylglycerol .

Role of PC in lung surfactant

Dipalmitoylphosphatidylcholine (DPPC, or dipalmitoylecithin). In DPPC, positions 1 and 2 on the glycerol are occupied by palmitate. DPPC, made and secreted by Type II pneumocytes, is the major lipid component of lung surfactant—the extracellular fluid layer lining the alveoli. Surfactant serves to decrease the surface tension of this fluid layer, reducing the pressure needed to reinflate alveoli, thereby preventing alveolar collapse (atelectasis). [Note: Surfactant is a complex mixture of lipids (90%) and proteins (10%), with DPPC being the major component for reducing surface tension.]
Respiratory distress syndrome (RDS) in preterm infants is associated with insufficient surfactant production and/or secretion, and is a significant cause of all neonatal deaths in Western countries.

Phosphatidylserine (PS):-

The primary pathway for synthesis of PS in mammalian tissues is provided by the base exchange reaction, in which the ethanolamine of PE is exchanged for free serine. This reaction, although reversible, is used primarily to produce the PS required for membrane synthesis.

Phosphatidylinositol (PI):-

PI is synthesized from free inositol and CDP-diacylglycerol. PI is an unusual phospholipid in that it often contains stearic acid on carbon 1 and arachidonic acid on carbon 2 of the glycerol. PI, therefore, serves as a reservoir of arachidonic acid in membranes and, thus, provides the substrate for prostaglandin synthesis when required.

Function of Phosphatidylinositol :-

Role of PI in signal transmission across membranes: The phosphorylation of membrane-bound phosphatidylinositol produces polyphosphoinositides. This occurs in response to the binding of a variety of neurotransmitters, hormones, and growth factors to receptors on the cell membrane.
Role of PI in membrane protein anchoring: Specific proteins can be covalently attached via a carbohydrate bridge to membrane-bound PI.

Phosphatidylglycerol and cardiolipin:-
Phosphatidylglycerol occurs in relatively large amounts in mitochondrial membranes and is a precursor of cardiolipin. It is synthesized by a two-step reaction from CDP-diacylglycerol and glycerol 3-phosphate.
Cardiolipin (diphosphatidylglycerol) is composed of two molecules of phosphatidic acid connected by a molecule of glycerol.

Plasmalogens:-

There are three major classes of plasmalogens, phosphatidal-ethanolamine, phosphatidal- choline, and phosphatidal-serine. These phospholipids have a fatty acid attached at carbon 1 in an ether linkage rather than an ester linkage. Myelin contains large amounts of ethanolamineplasmalogen, and heart muscle contains large amount of choline plasmalogen.
Platelet-activating factor (PAF):is a phosphatidacholin, which is very powerful chemical mediator. It has potent physiologic actions on a variety of cell types .e.g. it causes blood plate let aggregation and degranulation and was therefore originally called PAF.
Other effect of PAF include increasing airway and pulmonary edema in the lungs, serving as a major mediator of hypersensitivity, acute inflammatory reactions, and anaphylactic shock, and causing neutrophils and alveolar macrophages to generate superoxide radicals.

DEGREDATION OF PHOSPHOLIPIDS

e.g. Lecithin .
The lecithin composed of glycerol that have fatty acid in the carbon no.1 and fatty acid on carbon no.2 and phosphocholine on carbon no.3 .
By the action of the enzyme phospholipase A2, the fatty acid will be removed from the carbon no.2 and this lead to the formation of lysolecithin and fatty acid .
By the action of the enzyme phospholipase A1, the fatty acid will be removed from the carbon no.1 and this lead to the formation of glycerol phosphocholine and fatty acid.
By the action of the enzyme hydrolase, the choline will be removed and this lead to the formation of glycerol 3 phosphate and choline.