Pyruvate carboxylase catalyses

Pyruvate carboxylase catalyses the conversion of pyruvate to oxaloacetate using ATP and CO2. This is an important reaction both for gluconeogenesis (to bypass the pyruvate kinase reaction) and also for the normal function of the citric acid cyde. For the citric acid cycle to begin, one molecule each of oxaloacetate and acetyl CoA is required. If there is a shortage of oxaloacetate, the balance is restored by the action of pyruvate carboxylase. If, for example, oxaloacetate has been removed from the cycle to enter the amino acid synthesis pathways, it can simply be regenerated fiom pyruvate (31b). 

Nuclear relaxation studies of substrates and inhibitors have resulted in the detection of 10 enzyme-Mur-substrate and 4 enzyme-Mn-inhibitor bridge complexes possessing kinetic and thermodynamic properties consistent with their participation in enzyme catalysis. Three cases of a activation, by divalent cations, of enzyme-catalyzed enolization reactions (pyruvate carboxylase, yeast aldolase, v-xylose isomerase), and one case of 8 activation of an enzyme-catalyzed elimination reaction (histidine deaminase) have thereby been established, Thus, in each proven case, the enzyme-bound Mn coordinates an electronegative atom (Z) of the substrate, which is attached to a carbon atom one or two bonds away from the carbon atom which is to be deprotonated ... 

The enzyme that catalyzes this reaction is pyruvate carboxylase, an allosteric enzyme found in the mitochondria. Acetyl-CoA is an allosteric effector that activates pyruvate carboxylase. If high levels of acetyl-GoA are present (in other words, if there is more acetyl-GoA than is needed to supply the citric acid cycle), pyruvate (a precursor of acetyl-GoA) can be diverted to gluconeogenesis. (Oxaloacetate from the citric acid cycle can frequendy be a starting point for gluconeogenesis as well.) Magnesium ion (Mg +) and biotin are also required for effective catalysis. We have seen Mg + as a cofactor before, but we have not seen biotin, which requires some discussion. 

In all aerobic organisms, FA biosynthesis occurs via two different metabolic pathways (1) tricarboxylic acid cycle (TCA) or Krebs cycle and (2) reductive carboxylation pathway. Albert Szent-Gyorgyi (1893-1986, Hxmgary) discovered FA catalysis during his study (including on vitamin C) on cellular combustion process (TCA cycle) for which he was awarded the Noble Prize in Physiology or Medicine in 1937 (www.nobelprize.org). TCA involves CO2 fixation coupled with the conversion of pyruvate to oxaloacetate, the precursor to malate and fuma-rate (Fig. 8.3). Reductive CO2 fixation catalyzed by the enzyme pyruvate carboxylase xmder... 

---