II- Compound lipids: They composed of fatty acids + alcohol+ other substance which may be phosphorous (phosphlipids), proteins (lipoproteins), sugar (glycolipid) Phospholipids Phospholipids are classified according to alcohol content into: 1- Glycerophospholipids: alcohol is glycerol 2- Sphingophospholipids: alcohol is sphingosine

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

Cephalins: Their chemical structure is exactly as lecithin but they differ only in the base which may be: Ethanol amine so called: phosphatidyl ethanol amine Serine and so called phosphatidyl serine 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

Phosphatidyl ethanolamine (cephalin) Sources: brain tissues.

Phosphatidyl inositol: structure not required It is one of cell membrane lipids (but less common) In addition it plays a role in cell signaling

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.

Q: Classify each lipid

Phospholipids Phospholipids are lipids containing phosphate. They also contain alcohol (glycerol or sphingosine), fatty acids and base (choline, ethanolamine or serine). See the structures Sources: Exogenous: from diet e.g. eggs Endogenous: In all cell. Plasma levels: The average total phospholipids are about 200 mg/dl (60% lecithins, 25% cephalins and 15% sphingomyelins) Digestion and absorption: begins in the intestine Phospholipids either absorbed as such or are hydrolyzed by certain pancreatic phospholipases as follow: 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.

PLA2 releases arachidonic acid from C2 of glycerol PLA2 releases arachidonic acid from C2 of glycerol. Arachidonic acid enter in synthesis of prostaglandins and leukotriens which causes inflammation. 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.

Degradation of phospholipids: Lysolecithin or lysocephaline

If phospholipids absorbed as it is, they are usually absorbed with triglycerides and cholesterol. All are bound to protein to form chylomicrons (mainly TG + phospholipids + cholesterol + apoprotein).

Functions of phospholipids: 1- Enter in the structure of cell membranes 2- Help triglycerides transport (enter in the synthesis of chylomicron) . 3- Blood clotting: Cephalins enter in the formation of thromboplastin which is necessary for blood clotting. 4- Phospholipids act as lipotropic factors i.e. prevent accumulation of fats in liver hence prevent fatty liver. 5- Phospholipids in bile make cholesterol soluble. Their deficiency leads to cholesterol gallstones (see image A). 6- Dipalmitoyl lecithin act as lung surfactant, prevent alveolar collapse and allow air passage (see image B).

Image A) Choleserol gallstones

Phospholipid bilayer

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

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

Synthesis of Lecithin Lecithin Acyl CoA C)

B) Synthesis of sphingomyelins (not required, cancelled): Sphingomyeline is formed of sphingosine base, fatty acyl CoA, phosphate and choline. (Remembr structure, first lecture). Steps of synthesis: see figure 1- Palmitic acid is activated by CoA to give palmitoyl CoA. 2- Combination of palmitoyl CoA with serine to form 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 phospholipids: - Lecithin and cephalins are degraded by plasma phospholipases A1, A2 , C and D.(as before). -Sphigomyelin is degraded by sphingomyleinase   

Niemann-Pick disease: in children It is one of lipid storage disease in which harmful quantities of fatty substances, or lipids, accumulate in the spleen, liver, lungs, bone marrow, and brain 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 crortex cause dementia and seizers.

Not required