Biosynthesis of Glycerophospholipids Guide

Biosynthesis of Glycerophospholipids

The most abundant phospholipids are made from glycerol. Phospholipids are important components of membranes, and help transport triacylglycerols and cholesterol in the body. Typically, they have saturated fatty acids at carbon #1 (more than 90%) and unsaturated fatty acids at carbon #2 (more than 90%).

PL synthesisThere are a few differences in the lipids (and metabolic routes to making them) of eukaryotes and prokaryotes. We will not be concerned about distinguishing the routes of their synthesis. For our purposes, the routes are the same

Additional lipids contained eukaryotes beyond those for prokaryotes include phosphatidyl choline and phosphatidyl inositol. There are three routes to forming phosphatidic acid we will be concerned about:

Biosynthesis of Glycerophospholipids

1. From DHAP:

Biosynthesis of Glycerophospholipids

2. From Glycerol-3-phosphate:

 Biosynthesis of Glycerophospholipids

3. By phosphorylation of diacylglycerol (fat breakdown product):

Pathways of Glycerophospholipids

Your book shows several important metabolic pathways of Glycerophospholipids:

1. A general pathway outlining Glycerophospholipids biosynthesis :

Biosynthesis of Glycerophospholipids2. Synthesis of CDP-diacylglyerol from glycerol-3-phosphate and CTP: (CDP-diacylglycerol is a branch point in biosynthesis some of the glycerolipids)

Biosynthesis of Glycerophospholipids3. Synthesis of phosphatidyl serine, phosphatidyl ethanolamine, phosphatidyl glycerol, and cardiolipin:

Biosynthesis of Glycerophospholipids4. A pathway for synthesis of phosphatidyl choline:

Biosynthesis of Glycerophospholipids5. Interconversion of Phosphatidylserine, phosphatidyl ethanolamine, and phosphatidyl choline:

Biosynthesis of Glycerophospholipids

Methylation of phosphatidyl ethanolamine is accomplished with an activated derivative of methionine called S-adenosylmethionine. After the methyl group is donated, S-adenosylhomocysteine (AdoHcy) is generated. AdoMet and AdoHcy are shown in the top. Formation of AdoMet is depicted in the bottom.


Glycerophospholipids are not metabolically inert compounds, though it is not fully understood how and when substitutions and modifications of them occur. Infants with respiratory distress have a defect in metabolism of lung surfactant, a phospholipid in lung tissue.

Above it was pointed out that Glycerophospholipids have saturated fatty acids at the #1 position 90% of the time, and unsaturated fatty acids at the #2 position 90% of the time. Lung surfactant is unusual in having a saturated fatty acid (palmitate) at positions 1 and 2.

It is not known how this end result is achieved, but one way it might be made is through action of one or more phospholipases. Phospholipases hydrolyze specific bonds on phospholipids. Sites of action of phospholipases A1, A2, C, and D.

Action of Phospholipases

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