Question

Describe how newly synthesized fatty acids are incorporated into triacylglycerols.

(please type the answer, no handwriting, and maybe you can draw a diagram to help explain it !)

Answer 1

There are one of the two fates of fatty acids present inside the body. The ingested or synthesized fatty acids are either incorporated into the triacylglycerols (used as storage of metabolic energy) or into phospholipids (to form cell membrane).

There are basically three main pathways for biosynthesis of triacylglycerol; namely dihydroxyacetone phosphate pathway, the sn-glycerol-3-phosphate and monoacylglycerol pathway. The dihydroxyacetone phosphate pathway and the sn-glycerol-3-phosphate occur in adipose tissue and liver while monoacylglycerol pathway in intestines.

The most popular pathway of triacylglycerol synthesis is sn-glycerol-3-phosphate also called Kennedy pathway. About 90% of triacylglycerol in liver are synthesized by this pathway.

1. Description of the pathway (Kennedy pathway)

1. sn-glycerol-3-phosphate forms the original glycerol backbone of TAG.

2. sn-glycerol-3-phosphate is produced by glycolysis through action of glycerol kinase. Glycerol is produced de novo by a process of glyceroneogenesis through pyruvate.

3. The reaction occurs in endoplasmic reticulum. Enzyme glycerol-3-phosphate acyltransferase (GPAT) esterifies the precursor sn-glycerol-3-phosphate at position sn-1 using fatty acid coenzyme A ester. This results in formation of lysophosphatidic acid.

4. Enzyme acyl glycerophosphate acyltransferase (AGPAT) acylates the lysophosphatidic acid at sn-2 position forming a key intermediate in the biosynthesis of phosphatidic acid.

5. PAPs - Phosphatidate phosphatases or phosphatidic acid phosphohydrolases or lipid phosphate phosphatases, these enzymes remove the phosphate group from phosphatidic acid converting them into diacyl glycerol or 1,2-diacyl-sn-glycerol.

6. Enzyme diacylglycerol acyltransferases (DGAT) uses fatty acyl-CoA esters and acylates 1,2-diacyl-sn-glycerol converting it to triacyl-sn-glycerol.

Dihydroxyacetone-phosphate pathway for triacylglycerol biosynthesis

1. The reaction occurs in endoplasmic reticulum or in peroxisomes.

2. The Dihydroxyacetone-phosphate gets acylated by enzyme acyltransferase forming 1-acyl dihydroxyacetone-phosphate.

3. 1-acyl dihydroxyacetone-phosphate undergoes reduction by a oxido-reductase enzyme into lysophosphatidic acid.

4. The lysophosphatidic acid thereafter follows Kennedy pathway

5. Enzyme acyl glycerophosphate acyltransferase (AGPAT) acylates the lysophosphatidic acid at sn-2 position forming a key intermediate in the biosynthesis of phosphatidic acid.

6. PAPs - Phosphatidate phosphatases or phosphatidic acid phosphohydrolases or lipid phosphate phosphatases, these enzymes remove the phosphate group from phosphatidic acid converting them into diacyl glycerol or 1,2-diacyl-sn-glycerol.

7. Enzyme diacylglycerol acyltransferases (DGAT) uses fatty acyl-CoA esters and acylates 1,2-diacyl-sn-glycerol converting it to triacyl-sn-glycerol.

III. Monoacylglycerol pathway for triacylglycerol biosynthesis

1. In intestine about 75% of TAGs are produced by monoacylglycerol pathway.

2. 2-Monoacyl-sn-glycerols and free fatty acids released after catabolism of dietary triacylglycerols by the enzyme pancreatic lipase within the intestines are taken up by the enterocytes.

3. Enzyme acyl coenzyme A: monoacylglycerol acyltransferase acylates monoacylglycerols converting them into an intermediate sn-1,2-diacylglycerols

4. Finally, enzyme acyl coenzyme A: diacylglycerol acyltransferase (DGAT1) reacts with the sn-1,2-diacylglycerols to form triacylglycerols.