Question

One of the problems associated with obesity is the increased risk of Type 2 diabetes. High fatty acid concentration in the blood reduces glucose uptake and metabolism by skeletal muscle, increasing levels of blood glucose and insulin secretion (insulin resistance). Prolonged overproduction of insulin can cause failure of the \(\beta\) cells of the pancreas and Type 2 diabetes. This occurs in \(\sim 40 \%\) of obese individuals over \(5-10\) years. One way of regulating the concentration of fatty acids in blood is their reesterification into triacylglycerols. One type of antidiabetic drug (thiazolidinedione) acts on a nuclear receptor (PPAR \(\gamma 2\) ) facilitating the rate of fatty acid esterification in white adipose tissue. All of the following events are usually involved in the synthesis of triacylglycerols in adipose tissue except A. addition of a fatty acyl CoA to a diacylglycerol. B. addition of a fatty acyl CoA to a lysophosphatide. C. a reaction catalyzed by glycerol kinase. D. hydrolysis of phosphatidic acid by a phosphatase. E. reduction of dihydroxyacetone phosphate.

Short answer

Answer: B. addition of a fatty acyl CoA to a lysophosphatide.

Step-by-step solution

Formation of Glycerol-3-Phosphate

The backbone for triacylglycerol synthesis is glycerol-3-phosphate, which is formed from glycerol by glycerol kinase (C), or from dihydroxyacetone phosphate by reduction (E). Both of these reactions are involved in triacylglycerol synthesis.

Esterification of Fatty Acids

Fatty acids first need to be activated to form fatty acyl CoA. The fatty acyl CoA can then be sequentially esterified to the glycerol-3-phosphate. The first fatty acyl CoA is esterified at the 1-position, and the second fatty acyl CoA is esterified at the 2-position, forming phosphatidic acid.

Conversion of Phosphatidic Acid to Diacylglycerol

Phosphatidic acid is hydrolyzed (D) to remove a phosphate group, resulting in diacylglycerol. This step is necessary in the synthesis of triacylglycerols.

Esterification of the Third Fatty Acyl CoA

The third fatty acyl CoA is added (A) to the diacylglycerol, forming triacylglycerol. Now that we understand the steps involved in triacylglycerol synthesis, we can identify the odd one out.

Identifying the Odd Event

The only event that has not been mentioned in any of the steps is (B): addition of a fatty acyl CoA to a lysophosphatide. This reaction is not involved in the synthesis of triacylglycerols in adipose tissue. Therefore, the answer is: B. addition of a fatty acyl CoA to a lysophosphatide.