Principles of Biochemistry Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Biosynthesis of Carbohydrates in Animal Tissues
Intermediates of the citric acid cycle also serve as precursors for glucose

The biosynthetic pathway described above is used for the Synthesis of glucose not only from Pyruvate; it can also serve to synthesize glucose from various precursors of pyruvate or phosphoenolpyruvate (Fig. 20–1). The principal roles among these are played by The Citric Acid Cycle intermediates citrate, isocitrate, α-ketoglutarate, succinate, fumarate, and malate. All of these can undergo oxidation in The Citric Acid cycle to yield oxaloacetate, which is then converted into phosphoenolpyruvate by the action of phosphoenolpyruvate carboxykinase, as shown in Fig. 20–2. However, only three carbon atoms from each of the citric acid cycle intermediates can be incorporated into glucose.

It is important to note that, under normal conditions, acetyl-CoA is not used as a glucose precursor in animals because it cannot be converted into pyruvate. As we recall, the pyruvate dehydrogenase reaction is irreversible under cellular conditions (Section 16.2). Thus, Fatty acids with an even number of carbon atoms are not normally converted into net glucose in animals, because their oxidative degradation yields exclusively acetyl-CoA.