Question

explain why the carbons of even chain fatty acids can never be used to synthesize NET glucose, but that the 14C from labeled fatty acids will be found in glucose.

Answer 1

This is best explained by the following TCA cycle publ;ished in 1957, though this is oversimplified.

Fatty acids are broken down to acetyl-CoA by means of beta oxidation, whereas fatty acids are synthesized from acetyl-CoA outside the mitochondrion. These two pathways are distinct, not only in where they occur, but also in the reactions that occur, and the substrates that are used.

The two pathways are mutually inhibitory, preventing the acetyl-CoA produced by beta-oxidation from entering the synthetic pathway via the acetyl-CoA carboxylase reaction. It can also not be converted to pyruvate as the pyruvate decarboxylase reaction is irreversible.

Instead the acetyl-CoA produced by the beta-oxidation of fatty acids condenses with oxaloacetate, to enter the citric acid cycle. During each turn of the cycle, two carbon atoms leave the cycle as CO₂ in the decarboxylation reactions catalyzed by isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase. Thus each turn of the citric acid cycle oxidizes an acetyl-CoA unit while regenerating the oxaloacetate molecule with which the acetyl-CoA had originally combined to form citric acid. The decarboxylation reactions occur before malate is formed in the cycle. This is the only substance that can be removed from the mitochondrion to enter the gluconeogenic pathway to form glucose or glycogen in the liver or any other tissue.

There can therefore be no net conversion of fatty acids into glucose.

But the carbon atoms in fatty acid can end up in the glucose formed so there is the possibility of 14C in fatty acid ending up in the glucose.