Classification of Phospholipids Phospholipids are classified according to alcohol content into: Glycerophospholipids and Sphingophospholipids 1- Glycerophospholipids: alcohol is glycerol Glycerophospholipids composed of Glycerol, Two fatty acids, Phosphate group and Alcohol amine 2- Sphingophospholipids: alcohol is sphingosine Sphingophospholipids composed of sphingosine alcohol + ONE Fatty acid + phosphate + Choline

I- Glycerophospholipids OR

The most common glycerophospholipids are: 1- Phosphatidic acid: it is the simplest phosphlipid and doesn’t have specific functions 2- Lecithin: It is formed of glycerol, two fatty acids, phosphate and choline which is a nitrogenous base. It is phosphatidic acid + choline so it is called phosphatidylcholine Lecithin Phosphatidic acid

3- Phosphatidyl ethanolamine (Cephalin): its chemical structure is exactly as lecithin but choline is replaced by ethanolamine 4- Phosphatidyl serine

Phosphatidyl Serine is an important phospholipid which supports cell integrity - Found in high concentrations in the brain, levels of which decline with age. - It is essential for normal neuron structure and function and may play a critical role in maintaining concentration and memory

5- Phosphatidyl inositol: It is one of cell membrane lipids (but less common) In addition it plays a role in cell signaling (a group of events that lead to specific cellular response)

How do lipids behave in an aqueous environment? Phospholipids are amphipathic molecules. They aggregate to hide their hydrophobic tail inside and expose hydrophilic head to the outside.

Synthesis of glycerophospholipids: Liver is the site of synthesis (A) Synthesis of lecithin (phosphatidyl choline) and cephalin (phosphatidyl ethanolamine): Their synthesis needs 1- Glycerol activated by ATP (by glycerol kinase) giving glycerol-3-phosphate 2- Two fatty acids activated by CoA (by thiokinase) giving acyl CoA (active FA). 3- Choline (for synthesis of lecithin) or ethanolamine (for synthesis of cephalines) activated by CTP to give CDP choline or CDP ethanolamine.

Synthesis of Lecithin Lecithin Acyl CoA C)

B) Synthesis of phosphatidyl serine: Phosphatidylserine is formed when phosphatidylethanolamine reacts with serine, which replaces the ethanolamine moiety

Degradation of glycerophospholipids

Degradation of phospholipids: Lysolecithin or lysocephaline

Phospholipase A1: Act on ester bond in position 1: removes the first fatty acid from lecithin or cephalin producing lysolecithin or lysocephalin. Phospholipase A2 (PLA2)): act on position 2 removes the second fatty acid from lysolecithin or lysocephalin. Phospholipase C (phosphodiesterase): act on linkage between the glycerol and phosphate giving free glycerol and phosphate+base (phosphoryl base) Phospholipase D (phosphatase): act on linkage between phosphate and base giving free phosphate and free base.

Importance of PLA2 When PLA2 act on membrane phospholipids, it releases arachidonic acid from C2 of glycerol. Arachidonic acid enter in synthesis of prostaglandins and leukotriens which causes inflammation. The pathway is catalyzed by cycloxygenase enzyme (COX). This enzyme can be inhibited by aspirin. Cortison can inhibit PLA2 PLA2 are commonly found in mammalian tissues as well as insect and snake venom. Due to the increased presence and activity of PLA2 resulting from a snake or insect bite, aracidonic acid is released from the phospholipid membrane . As a result, inflammation and pain occur at the site of insect bite.

NSAIDs (means non steroidal anti-inflammtory drugs e. g NSAIDs (means non steroidal anti-inflammtory drugs e.g. aspirin) inhibits cycloxygenase (COX). While, cortison inhibits PLA2.

Importance of phospholipase C (PLC): When PLC act on phosphatidyl inositol 4,5 biphosphate, it release inositol triphosphate (IP3) and DAG which are important second messengers

Functions of phospholipids: 1- Enter in the structure of cell membranes 2- Component of lipoproteins. 3- Blood clotting: Cephalins enter in the formation of thromboplastin which is necessary for blood clotting. 4- Phospholipids as a component of bile in bile make cholesterol soluble. Their deficiency leads to cholesterol gallstones (see image A). 5- Dipalmitoyl lecithin act as lung surfactant, prevent alveolar collapse and allow air passage (see image B).

Respiratory distress syndrome in the newborn: Lung surfactant is the extracellular fluid layer lining the alveoli. Surfactants serve to decrease the surface tension of this fluid layer, reducing the presure needed to reinflate alveoli and prevent alveolar collapse. Dipalmitoylphosphatidylcholine (DPPC) or called (dipalmitoyl lecithin, DPL) serves as the major component of lung surfactant in adults, allowing the lungs to function normally. This phospholipid develops in the fetus after 30 weeks of gestation. Premature (preterm) infants do not have an adequate amount of this phospholipid. As a result, acute respiratory distress syndrome can occur and associated with insufficient surfactant and cause neonatal death.

Image A) Choleserol gallstones

Phospholipid bilayer

Image B: alveolar collapse in absence of surfactant (dipalmitoyl lecithin)

2-Sphingophospholipids Sphingomyelin: it is a sphingophospholipid Not contain glycerol but contain alcohol called : sphingosine, Fatty acid is attached to amino group of sphingosine and phosphorylcholine (phosphate + choline) is attached to the last OH group. Sources: present in high amount in brain and nerve tissues.

Synthesis of sphingomyelins: Sphingomyelin is formed of sphingosine base, fatty acyl CoA, phosphate and choline. Steps of synthesis: 1- Palmitic acid is activated by CoA to give palmitoyl CoA. 2- Combination of palmitoyl CoA with serine to form sphingosine derivative (ketosphinganine) which after modification gives sphingosine base. 3- Then sphingosine reacts with acyl CoA to form ceramide 4- Ceramide then reacts with lecithin (phosphatidyl choline) to form sphingomyelin and diacylglycerol.   

Degradation of sphingomyelin: by sphingomyelinase enzyme in lysosome giving ceramide and phosphatidyl choline Niemann-Pick disease: in children Niemann-Pick disease results from genetic absence of sphingomyelinase enzyme (the enzyme that breakdown excess sphingomylein). The absence of this enzyme leads to accumulation of sphingomyelin in liver and spleen leading to enlargement of these organs and may cause reduced appetite, abdominal distension and pain, and the enlarged spleen may trap platelets and other blood cells, leading to reduced numbers of these cells in the circulation. The disease is fatal in early life. Sphingomyelin accumulation in the brain results in unsteady gait (ataxia), slurring of speech and difficult swallowing (dysphagia). More widespread disease involving the cerebral cortex cause dementia and seizers.