Classical scheme of the interconversion between glucose and fatty acids in humans.

A While the conversion of glucose into fatty acids is possible, the product of β-oxidation of even-chain fatty acids, acetyl-CoA, can only enter the TCA cycle by reaction with oxaloacetate to citrate. However, in order to replenish the oxaloacetate consumed in this reaction, the TCA cycle has to be used resulting in the release of two carbon atoms in form of carbon dioxide. Hence, while two carbon atoms enter the TCA cycle in form of acetyl-CoA two others are lost and a net production of oxaloacetate which would be required for gluconeogenesis is not possible. B In some organisms the carbon releasing steps of the TCA cycle can be bypassed using the glyoxylate shunt (thick dotted reactions). In consequence, one mole of oxaloacetate can be produced from two mole of acetyl-CoA, allowing for gluconeogenesis from fatty acids. A list of abbreviations can be found in Table S1.