An obese man has been on a strict diet with very small amounts of carbohydrates, yet serum chemistries show a low-normal level of glucose in his blood stream. Which of the following is the source of the majority of the newly synthesized glucose?

A. Amino acids from protein degradation
B. Ethanol synthesized by bacteria
C. Fatty acids from fat breakdown
D. Glycerol from fat breakdown
E. Purine catabolism

My guess is D. Glycerol from fat breakdown

That is correct, D.

The correct answer is D. The amino acid degradation pathways that produce oxaloacetate and pyruvate can be used to synthesize glucose and are commonly stressed in biochemistry books. These pathways are important in true starvation. Also stressed in biochemistry books is that acetyl-CoA cannot be used for gluconeogenesis, and thus fatty acids are not gluconeogenic. But this does not mean that "fat" cannot be used to make at lease some glucose, since the stored fat is predominately in the form of triglycerides, and the glycerol backbone is glycogenic. Specifically, glycerol can be phosphated by glycerol kinase (which uses ATP) to form glycerol-3-phosphate, which can in turn enter the gluconeogenic pathway via oxidation to dihydroxyacetone phosphate. This pathway contributes about 80% of the glucose in dieting obese individuals, and about 20% of the glucose (behind the amino acid pathways) in truly starving individuals.
Many amino acids (choice A) are gluconeogenic, but these pathways are more important in starvation than in dieting.

Ethanol (choice B) is not gluconeogenic, but is produced in small amounts by gut bacteria.

Fatty acids from fat (choice C) that undergo beta-oxidation produce acetyl CoA, which does not make glucose.

Purine catabolism (choice E) produces the waste product uric acid, which is excreted in urine.