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. Glycerol-3-phosphate for triacylglycerol synthesis A. is always formed by reduction of dihydroxyacetone phosphate. B. can be formed in liver by glyceroneogenesis but not in adipose tissue. C. derives its carbons primarily from amino acids in the fed state. D. can be synthesized only in the presence of phosphoenolpyruvate carboxykinase. E. is derived primarily from glucose via glycolysis in the fed state.

Short answer

Answer: In the fed state, glycerol-3-phosphate is derived primarily from glucose via glycolysis.

Step-by-step solution

Understand Glycerol-3-phosphate synthesis

Glycerol-3-phosphate is an important molecule in the synthesis of triacylglycerols. It can be formed through different metabolic pathways, including glycolysis, gluconeogenesis, and glyceroneogenesis. The major source of glycerol-3-phosphate synthesis varies depending on the fed or fasting state of the organism. In the fed state, glycerol-3-phosphate is primarily derived from glucose via glycolysis. The glucose is first converted to dihydroxyacetone phosphate and then reduced to form glycerol-3-phosphate. In the fasting state or under certain conditions, glycerol-3-phosphate may also be generated from other sources, such as glyceroneogenesis, which is the synthesis of glycerol-3-phosphate from non-carbohydrate precursors like amino acids. In this case, phosphoenolpyruvate carboxykinase (PEPCK) plays a vital role in the glyceroneogenesis pathway.

Evaluate each statement

A. Glycerol-3-phosphate is not always formed solely by the reduction of dihydroxyacetone phosphate. It can also be formed through glyceroneogenesis. So, this statement is incorrect. B. Glycerol-3-phosphate can be formed in both liver and adipose tissue. In the liver, it is primarily derived from glycolysis, while in adipose tissue, glyceroneogenesis is the major pathway. Therefore, this statement is incorrect. C. In the fed state, glycerol-3-phosphate primarily derives its carbons from glucose via glycolysis, not amino acids. So, this statement is incorrect. D. Glycerol-3-phosphate can be synthesized in the presence of PEPCK, but it is not the only requirement. PEPCK plays a role in glyceroneogenesis, which is one pathway for glycerol-3-phosphate synthesis. Thus, this statement is incorrect. E. In the fed state, glycerol-3-phosphate is indeed derived primarily from glucose via glycolysis. Since this statement is accurate, the correct answer is E.