Anaplerotic effect

By contrast, acetyl CoA does not have anaplerotic effects in animal metabolism. Its carbon skeleton is completely oxidized to CO2 and is therefore no longer available for biosynthesis. Since fatty acid degradation only supplies acetyl CoA, animals are unable to convert fatty acids into glucose. During periods of hunger, it is therefore not the fat reserves that are initially drawn on, but proteins. In contrast to fatty acids, the amino acids released are able to maintain the blood glucose level (see p. 308). 

With two exceptions (lysine and leucine see below), all of the proteinogenic amino acids are also glucogenic. Quantitatively, they represent the most important precursors for gluconeogenesis. At the same time, they also have an anaplerotic effect—1. e., they replenish the tricarboxylic acid cycle in order to feed the anabolic reactions that originate in it (see p. 138). 

Substrate availability for certain reactions can be optimized by anaplerotic ( topping-up ) reactions. For example, citrate synthase is a key control point of the TCA cycle. The co-substrates of citrate synthase are acetyl-CoA and oxaloacetate (OAA) and clearly, restriction in the availability of either substrate will decrease the rate of the citrate synthase reaction. Suppose, for example, a situation arises when acetyl-CoA concentration is significantly higher than that of OAA, the concentration of the latter can be topped-up and the concentration of acetyl-CoA simultaneously reduced by diverting some of the pyruvate away from acetyl-CoA synthesis (via pyruvate dehydrogenase) to OAA synthesis (via pyruvate carboxylase) as shown in Figure 3.1. The net effect is to balance the relative concentrations of the two co-substrates and thus to promote citrate synthase activity. 

Answer Oxaloacetate depletion would tend to inhibit the citric acid cycle. Oxaloacetate is present at relatively low concentrations in mitochondria, and removing it for gluconeogenesis would tend to shift the equilibrium for the citrate synthase reaction toward oxaloacetate. However, anaplerotic reactions (see Fig. 16-15) counter this effect by replacing oxaloacetate. 

Fig. 41.13. The purine nucleotide cycle. Using a combination of biosynthetic and salvage enzymes, the net effect is the conversion of aspartate to fumarate plus ammonia, with the fumarate playing an anaplerotic role in the muscle.

Noguchi Y Young JD, Aleman JO, Hansen ME, Kelleher JK, Stephanopoulos G (2009) Effect of anaplerotic fluxes and amino acid availability on hepatic lipoapoptosis. J Biol Chem 284, 33425-36. 

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