Intermediates in the citric acid cycle are involved in many other metabolic pathways of the cell, including amino acid metabolism (see below), gluconeogenesis, and fatty acid metabolism (see here and here). Thus, the amounts of citric acid cycle intermediates will vary according to the metabolic needs of the cell. Replacement of citric acid cycle intermediates occurs via anaplerotic pathways. These pathways function in most cells to keep intramitochondrial concentration of citric acid cycle intermediates fairly constant with time. Figure 14.18 depicts several anaplerotic pathways and these are summarized below:

Oxaloacetate - from transamination of aspartate, phosphoenolpyruvate (PEP carboxylase), and pyruvate (pyruvate carboxylase).

Malate - from pyruvate (malic enzyme)

-Ketoglutarate - from transamination of glutamate

Note that because the citric acid cycle is cyclic, increasing the concentration of one of the intermediates (such as oxaloacetate) has the ultimate effect of increasing the concentration of the other intermediates in the cycle as well.