Glycerophospholipids

- Oct 01, 2020-

Glycerophospholipids are the most abundant phospholipids in the body. In addition to constituting biological membranes, they are also a component of bile and membrane surface active substances, and are involved in the recognition and signal transduction of proteins by cell membranes. 

The basic structure of glycerophospholipid is phosphatidic acid and the substituent group (X) connected with phosphoric acid; glycerophospholipid can be divided into many categories due to the different substituent groups, among which the important ones are:  Choline + phosphatidic acid——→ Phosphatidylcholine (phosphatidylcholine) is also called lecithin (ethanolamine) + phosphatidic acid-→ phosphatidylethanolamine (phosphatidylethanolamine) is also called cephain (serine) + phosphatidic acid-→ phospholipid Phosphatidylserine (glycerol) + phosphatidic acid-→ phosphatidylglycerol (phosphatidylglycerol)  Inositol (inositol) + phosphatidic acid-→ phosphatidylinositol (phosphatidylinositol)

Cardiolipin (cardiolipin) is formed by combining C1 and C3 of glycerol with two molecules of phosphatidic acid. Cardiolipin is an important component of mitochondrial inner membrane and bacterial membrane, and it is the only phospholipid molecule with antigenicity.

In addition to the above 6 types, the fatty acyl group at position 1 of glycerol in the glycerophospholipid molecule is replaced by a long-chain alcohol to form ethers, such as plasmalogen (plasmalogen) and platelet activating factor (PAF), which are all glycerophospholipids.

(2) Synthesis of glycerophospholipids The whole process of synthesis can be divided into three stages, namely, raw material source, activation and glycerophospholipid production. The synthesis of glycerophospholipids is carried out on the endoplasmic reticulum of the cytoplasmic slip surface, processed by the Golgi apparatus, and finally can be used by tissue biomembranes or become lipoprotein secreting cells. Various tissues of the body (except mature red blood cells) can undergo phospholipid synthesis.

1. Source of raw materials :The raw materials for the synthesis of glycerophospholipids are phosphatidic acid and substituted groups. Phosphatidic acid can be produced from glycerol and fatty acids produced by the conversion of sugars and lipids (see Triglyceride Synthesis and Metabolism for details), but most of the fatty acids at the C2 position of glycerol are essential fatty acids and require food supplies. Choline and ethanolamine in the substituted group can be converted into serine in the body or supplied by food.  Serine——→Ethanolamine——→Choline

2. Activation Before the synthesis of phosphatidic acid and substituent groups, one of the two must be activated by CTP and carried by CDP. Choline and ethanolamine can generate CDP-choline and CDP-ethanolamine, and phosphatidic acid can generate CDP-glycerol. Diester.

3. Formation of glycerophospholipids 1) Phosphatidylcholine and phosphatidylethanolamine are produced by activated CDP-choline, CDP-ethanolamine and diglycerides. In addition, phosphatidylethanolamine can be converted into phosphatidylcholine by donating a methyl group with adenosylmethionine in the liver. Different biosynthesis pathways of phosphatidylcholine are different.

2) Phosphatidylserine The synthesis of phosphatidylserine in vivo is generated by the acyl exchange reaction activated by Ca2+, and phosphatidylserine and ethanolamine are generated by the reaction of phosphatidylethanolamine and serine.  Phosphatidylethanolamine + Serine ——→ Phosphatidylserine + ethanolamine

3) Phosphatidylinositol, phosphatidylglycerol and cardiolipin are produced by the reaction of activated CDP-diglyceride with corresponding substituent groups. Another way to synthesize cardiolipin.

4) Plasmalogen and platelet activating factor The synthesis process of plasmalogen and platelet activating factor is similar to the above-mentioned phospholipid synthesis process, the difference is that before phosphatidic acid is synthesized, dihydroxyacetone phosphate, an intermediate product of sugar metabolism, is converted to fatty acyl phosphate After dihydroxyacetone, the first fatty acyl group is replaced by a molecule of long-chain fatty alcohol, and then the phosphatidic acid derivatives are synthesized through steps such as reduction (for H from NADPH) and transacyl. This product replaces phosphatidic acid as the starting material and synthesizes choline or ethanolamine plasmalogen along the triglyceride pathway. The difference between platelet activating factor and plasmalogen is that long-chain fatty alcohols are saturated long-chain alcohols, and the fatty acyl group at position 2 is the simplest acetyl group.

(3) Decomposition of glycerophospholipids There are some phospholipases that can hydrolyze glycerophospholipids in the organism, the main ones are phospholipases A1, A2, B, C and D, which specifically act on the various ester bonds within the phospholipid molecule. Different products are formed. This process is also the transformation process of glycerophosphate. 

1. Phospholipase A1 is widely distributed in nature, mainly in the lysosome of cells, in addition to snake venom and some microorganisms, it can catalyze the cleavage of the first ester bond of glycerophospholipid, and the products are fatty acids and lysophospholipids2. 

2. Phospholipase A2 is ubiquitously present in the cell membranes and mitochondrial membranes of various animal tissues. It can hydrolyze the second ester bond in the glycerophospholipid molecule. The products are lysophospholipid 1 and its product fatty acids, glycerophosphocholine or glycerophosphoethanolamine.  Lysophospholipids are a class of properties with strong surface activity, which can rupture red blood cells and other cell membranes, causing hemolysis or cell necrosis. When the fatty acid is removed by the action of phospholipase B, it is converted into glycerophosphocholine or glycerophosphoethanolamine, which loses the function of dissolving cell membranes. 

3. Phospholipase C exists in cell membranes and certain cells, and specifically hydrolyzes the phosphate bond at position 3 in the glycerophospholipid molecule, resulting in the release of phosphocholine or Colamine Acid Phosphate, and the remaining components in the target molecule . 

4. Phospholipase D mainly exists in plants and animal brain tissues. It catalyzes the ester bond between phosphoric acid and substituent groups (such as choline, etc.) in phospholipid molecules to release substituent groups.