Principles of Biochemistry Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Lipid Biosynthesis
The biosynthesis of triacylglycerols and glycerophospholipids begins with common precursors.

In animal Tissues, the Biosynthesis of triacylglycerols and major Phospholipids—phosphatidylethanolamine and phosphatidylcholine—begins with two common precursors and shares several initial steps. These common precursors are fatty acyl-CoA esters and glycerol 3-phosphate. Glycerol phosphate can be formed via two pathways. During Glycolysis, it is produced from dihydroxyacetone phosphate through the action of the cytoplasmic NAD-dependent enzyme glycerol phosphate dehydrogenase:

Class="center">Dihydroxyacetone phosphate + NADH + H⁺⇄

⇄ L-glycerol-3-phosphate + NAD⁺.

Alternatively, glycerol phosphate can be formed from glycerol through the action of glycerol kinase (Sec. 14.13):

ATP + Glycerol →

→ Glycerol-3-phosphate + ADP.

The other precursors for triacylglycerols are fatty acid CoA derivatives, which are produced with the help of acyl-CoA synthetases (Sec. 18.2):

Fatty acid + ATP +

+ CoA—SH → Acyl—S—CoA +

+ AMP + PP_i

In the first step of triacylglycerol biosynthesis, two free hydroxyl groups of glycerol phosphate are acylated by two molecules of fatty acyl-CoA derivatives to yield diacylglycerol 3-phosphate (Fig. 21-13):

Diacylglycerol 3-phosphate (more commonly called phosphatidic acid) is found in Cells only in trace amounts; however, it serves as a crucial intermediate in Lipid Biosynthesis. During triacylglycerol synthesis, phosphatidate is hydrolyzed by phosphatidate phosphatase to yield 1,2-diacylglycerol (Fig. 21-13):

Phosphatidate + H₂O →

→ 1,2-diacylglycerol + P_i.

By reacting with a third molecule of a fatty acyl-CoA derivative, diacylglycerol is subsequently converted into triacylglycerol:

Fatty acyl-CoA derivative +

+ 1,2-diacylglycerol →

→ Triacylglycerol + CoA—SH.

The formation of each ester bond in triacylglycerols requires a significant amount of Free energy. For an ester bond to form, the fatty acid must first be activated by conversion into a CoA ester; this reaction requires the energy of two high-energy phosphate bonds, as it is driven by the pyrophosphate Cleavage of ATP followed by the subsequent Hydrolysis of the resulting pyrophosphate.

Fig. 21-13. Synthesis of diacylglycerols. The two fatty acid residues enter the reaction sequentially. Typically, two different long-chain fatty acid residues are incorporated into the R₁ and R₂ positions. It should be noted that in the diacylglycerol phosphate molecule, the length of the fatty acyl residues significantly exceeds the dimensions of the glycerol phosphate molecule (Sec. 12.2).