Textbook - BIOLOGICAL CHEMISTRY - Hubsky Yu.I. - 2000

Chapter III. METABOLISM OF MAJOR CLASSES OF BIOMOLECULES

CHAPTER 15. LIPID METABOLISM. II. BIOSYNTHESIS OF TRIACYGLYCEROLS AND COMPLEX LIPIDS

15.2. BIOSYNTHESIS OF TRIACYLGLYCEROLS

Triacylglycerols (neutral fats) are Lipids that constitute the bulk of dietary lipids and are most abundant in adipocytes of adipose tissue, where they serve as a metabolic fuel reserve. The amount of neutral fats in the body of an adult weighing 70 kg averages 10-15 kg. In addition to adipose tissue, the Biosynthesis of triacylglycerols also occurs in limited amounts in other Tissues, notably the Liver, intestine, and mammary gland during Lactation.

The metabolic precursors in The biosynthesis of triacylglycerols are activated Fatty acids (acyl-CoA) and glycerol-3-phosphate, which in turn are supplied via glucose oxidation.

Class="center">ENZYMATIC REACTIONS OF triacylglycerol synthesis

1. Formation of the activated form of glycerol — glycerol-3-phosphate (α-glycerophosphate).

This process can occur via one of two mechanisms:

1.1. By phosphorylation of glycerol involving the enzyme glycerol phosphokinase (see also Chapter 14, Section 14.3):

1.2. By reduction of dihydroxyacetone phosphate, an intermediate of glycolytic glucose Cleavage. The reaction is catalyzed by NADH-dependent glycerol-3-phosphate dehydrogenase (α-glycerophosphate dehydrogenase):

2. Acylation of glycerol-3-phosphate to form phosphatidic acid utilizing two molecules of activated fatty acids — acyl-CoA. The process occurs in two stages:

2.1. The first acylation involving the enzyme glycerol-3-phosphate acyltransferase with The formation of 1-acylglycerol-3-phosphate (lysophosphatidate).

2.2. The second acylation involving the enzyme 1-acylglycerol-3-phosphate acyltransferase with the formation of 1,2-diacylglycerol-3-phosphate (phosphatidic acid).

An unsaturated fatty acid residue takes part in this acylation.

3. Hydrolysis of phosphatidic acid to 1,2-diacylglycerol (diglyceride) involving the enzyme phosphatidate phosphohydrolase:

4. Acylation of 1,2-diacylglycerol with a third acyl-CoA molecule (enzyme diacylglycerol acyltransferase) to yield triacylglycerol.

Features of triacylglycerol biosynthesis in adipocytes

Adipose tissue is virtually devoid of the enzyme glycerol phosphokinase; therefore, the primary source of glycerol-3-phosphate in adipocytes is the reduction of dihydroxyacetone phosphate supplied through the glycolytic breakdown of glucose.

Thus, Lipogenesis in adipose tissue heavily relies on the supply of glucose to adipocytes. Since the permeability of adipocyte membranes to glucose is Insulin-dependent, normal insulin production by the Pancreas is an essential prerequisite for the biosynthesis of triacylglycerols in adipocytes.