Principles of Biochemistry, Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Lipid Biosynthesis
The biosynthesis of phosphoglycerols requires the groups that form the polar head groups of the molecules

We now turn to the synthesis of Membrane Lipids. Phosphoglycerols such as phosphatidylethanolamine and phosphatidylcholine—the major components of membrane lipids—are likewise synthesized from 1,2-diacylglycerols. The sequence of these reactions is outlined in Fig. 21-15. During The formation of phosphoglycerols, specific "HEAD groups" (Section 12.5) are attached to their molecules via an intermediate enzymatic reaction not yet discussed. In the course of phosphatidylethanolamine synthesis, the phosphoethanolamine head group is attached to the molecular tail through the interaction of diacylglycerol with cytidine diphosphate ethanolamine, which is formed from three precursors: ethanolamine, ATP, and cytidine triphosphate (CTP, Fig. 14-18). First, ethanolamine kinase catalyzes the formation of phosphoethanolamine:

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Fig. 21-15. General pathway for the synthesis of glycerol-containing lipids, showing that triacylglycerols and the two major glycerol-containing Phospholipids share common precursors. The Enzymes involved in the Biosynthesis OF PHOSPHOGLYCERIDES from diacylglycerols are tightly bound to The Endoplasmic reticulum.

Phosphoethanolamine then reacts with CTP to yield cytidine diphosphate ethanolamine and pyrophosphate (Fig. 21-16). This reaction is catalyzed by phosphoethanolamine cytidylyltransferase:

The attachment of the polar head group to diacylglycerol to form phosphatidylethanolamine (Fig. 21-17) is mediated by the enzyme ethanolamine phosphotransferase:

Just as ATP transfers activated phosphate groups and CDP-glucose transfers glucosyl groups, CDP-ethanolamine transfers activated phosphoethanolamine groups. Here we see another example of how NUCLEOTIDES can serve as carriers of specific chemical groups in cellular METABOLISM. Cytidine nucleotides are specific for this reaction: no other nucleoside 5′-triphosphates can replace CTP in animal Tissues. The key role of cytidine nucleotides in Lipid Biosynthesis was first discovered by Eugene P. Kennedy.

Fig. 21-16. A. Formation of cytidine diphosphate ethanolamine. Cytidine diphosphate Choline is formed by an analogous reaction from phosphocholine (B).

Fig. 21-17. Formation of phosphatidylethanolamine from CDP-ethanolamine and diacylglycerol. The zigzag lines represent the long hydrocarbon tails of fatty acid residues.