Biological Chemistry - Berezov, T. T., Korovkin, B. F. 1998

Lipid Metabolism
Biosynthesis of Triglycerides

It is known that The rate of FATTY ACID Biosynthesis is largely determined by the rate of triglyceride and phospholipid formation, since free Fatty acids are present in Tissues and Blood Plasma in small amounts and do not normally accumulate.

The synthesis of triglycerides proceeds from glycerol and fatty acids (mainly stearic, palmitic, and oleic acids). The biosynthetic pathway of triglycerides in tissues involves The formation of $\alpha$-glycerophosphate (glycerol-3-phosphate) as an intermediate compound.

In the Kidneys, as well as in the intestinal wall where The activity of the enzyme glycerokinase is high, glycerol is phosphorylated at the expense of ATP to yield glycerol-3-phosphate:

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In adipose tissue and Muscles, due to the very low activity of glycerokinase, the formation of glycerol-3-phosphate is primarily coupled with the processes of Glycolysis and Glycogenolysis. It is known that the glycolytic breakdown of glucose produces dihydroxyacetone phosphate (see Chapter 10). The latter, in the presence of cytoplasmic glycerol-3-phosphate dehydrogenase, is capable of being converted into glycerol-3-phosphate:

It has been noted that if the glucose content in Adipose tissue is low (e.g., during starvation), only an insignificant amount of glycerol-3-phosphate is formed, and the free fatty acids released during lipolysis cannot be utilized for the resynthesis of triglycerides, thus leaving the adipose tissue. Conversely, the activation of glycolysis in adipose tissue promotes the accumulation of triglycerides and their constituent fatty acids therein. Both pathways of glycerol-3-phosphate formation are observed in the Liver.

Glycerol-3-phosphate formed via either pathway is sequentially acylated by two molecules of a fatty acid CoA derivative (i.e., the "active" forms of fatty acids—acyl-CoA). As a result, phosphatidic acid (phosphatidate) is formed:

As noted, the acylation of glycerol-3-phosphate proceeds sequentially, i.e., in 2 stages. First, glycerol-3-phosphate acyltransferase catalyzes the formation of lysophosphatidate (1-acylglycerol-3-phosphate), and then 1-acylglycerol-3-phosphate acyltransferase catalyzes the formation of phosphatidate (1,2-diacylglycerol-3-phosphate)*.

Next, Phosphatidic acid is hydrolyzed by phosphatidate phosphohydrolase to 1,2-diglyceride (1,2-diacylglycerol):

Then 1,2-diglyceride is acylated by a third acyl-CoA molecule and converted into triglyceride (triacylglycerol). This reaction is catalyzed by diacylglycerol acyltransferase:

The synthesis of triglycerides (triacylglycerols) in tissues takes into account two pathways for the formation of glycerol-3-phosphate and the possibility of triglyceride synthesis in the Small Intestine wall from ß-monoglycerides entering the intestinal lumen in large amounts following the Digestion of dietary fats. Fig. 11.6 illustrates the glycerophosphate, dihydroxyacetone phosphate, and ß-monoglyceride (monoacylglycerol) pathways of triglyceride synthesis.

* Phosphatidic acid (phosphatidate) has been found in many tissues, albeit in trace amounts. Only in the liver does it account for 1% of all Phospholipids.

Fig. 11.6. Biosynthesis of triglycerides (triacylglycerols).

It has been established that most Enzymes involved in The biosynthesis of triglycerides are located in The Endoplasmic reticulum, and only some, such as glycerol-3-phosphate acyltransferase, are found in the Cell/35.html">Mitochondria.