Phosphoenolpyruvate carboxylase (also known as PEP carboxylase, PEPCase, or PEPC; EC 4.1.1.31, PDB ID: 3ZGE) is an enzyme in the family of carboxy-lyases found in plants and some bacteria that catalyzes the addition of bicarbonate (HCO3−) to phosphoenolpyruvate (PEP) to form the four-carbon compound oxaloacetate and inorganic phosphate:[1] This reaction is used for carbon fixation in CAM (crassulacean acid metabolism) and C4 organisms, as well as to regulate flux through the citric acid cycle (also known as Krebs or TCA cycle) in bacteria and plants.

The PEP carboxylase enzyme is present in plants and some types of bacteria, but not in fungi or animals (including humans).

[2] The genes vary between organisms, but are strictly conserved around the active and allosteric sites discussed in the mechanism and regulation sections.

[3] The crystal structure of PEP carboxylase in multiple organisms, including Zea mays (maize), and Escherichia coli has been determined.

[3] The overall enzyme exists as a dimer-of-dimers: two identical subunits closely interact to form a dimer through salt bridges between arginine (R438 - exact positions may vary depending on the origin of the gene) and glutamic acid (E433) residues.

[1] This metal ion can be magnesium, manganese or cobalt depending on the organism,[1][2] and its role is to coordinate the phosphoenolpyruvate molecule as well as the reaction intermediates.

[1][2] The mechanism proceeds in two major steps, as described below and shown in figure 2: The metal cofactor is necessary to coordinate the enolate and carbon dioxide intermediates; the CO2 molecule is only lost 3% of the time.

However, at higher temperatures and lower CO2 concentrations, RuBisCO adds oxygen instead of carbon dioxide, to form the unusable product glycolate in a process called photorespiration.

This is then converted back to pyruvate (through a malate intermediate), to release the CO2 in the deeper layer of bundle sheath cells for carbon fixation by RuBisCO and the Calvin cycle.

[1][12] The main allosteric inhibitors of PEP carboxylase are the carboxylic acids malate (weak) and aspartate (strong).

Additionally, increased glycolysis means a higher supply of PEP is available, and thus more storage capacity for binding CO2 in transport to the Calvin cycle.