PEP carboxylase is mainly subject to two levels of regulation: phosphorylation and allostery.
Figure 3 shows a schematic of the regulatory mechanism.

Phosphorylation by phosphoenolpyruvate carboxylase kinase turns the enzyme on, whereas phosphoenolpyruvate carboxylase phosphatase turns it back off.
Both kinase and phosphate are regulated by transcription.
It is further believed that malate acts as a feedback inhibitor of kinase expression levels, and as an activator for phosphatase expression (transcription).
Since oxaloacetate is converted to malate in CAM and C₄ organisms, high concentrations of malate activate phosphatase expression - the phosphatase subsequently de-phosphorylates and thus de-actives PEP carboxylase, leading to no further accumulation of oxaloacetate and thus no further conversion of oxaloacetate to malate.
Hence malate production is down-regulated.

The main allosteric inhibitors of PEP carboxylase are the carboxylic acids malate (weak) and aspartate (strong).
Since malate is formed in the next step of the CAM and C₄ cycles after PEP carboxylase catalyses the condensation of CO₂ and PEP to oxaloacetate, this works as a feedback inhibition pathway.
Oxaloacetate and aspartate are easily inter-convertible through a transaminase mechanism; thus high concentrations of aspartate are also a pathway of feedback inhibition of PEP carboxylase.

The main allosteric activators of PEP carboxylase are acetyl-CoA and fructose-1,6-bisphosphate (F-1,6-BP).
Both molecules are indicators of increased glycolysis levels, and thus positive feed-forward effectors of PEP carboxylase.
They signal the need to produce oxaloacetate to allow more flux through the citric acid cycle.
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.
It is also noteworthy that the negative effectors aspartate competes with the positive effector acetyl-CoA, suggesting that they share an allosteric binding site.

Studies have shown that energy equivalents such as AMP, ADP and ATP have no significant effect on PEP carboxylase.

The magnitudes of the allosteric effects of these different molecules on PEP carboxylase activity depend on individual organisms.
PEP carboxylase is mainly subject to two levels of regulation: phosphorylation and allostery. Figure 3 shows a schematic of the regulatory mechanism. 
Phosphorylation by phosphoenolpyruvate carboxylase kinase turns the enzyme on, whereas phosphoenolpyruvate carboxylase phosphatase turns it back off. Both kinase and phosphate are regulated by transcription. It is further believed that malate acts as a feedback inhibitor of kinase expression levels, and as an activator for phosphatase expression (transcription). Since oxaloacetate is converted to malate in CAM and C₄ organisms, high concentrations of malate activate phosphatase expression - the phosphatase subsequently de-phosphorylates and thus de-actives PEP carboxylase, leading to no further accumulation of oxaloacetate and thus no further conversion of oxaloacetate to malate. Hence malate production is down-regulated.
The main allosteric inhibitors of PEP carboxylase are the carboxylic acids malate (weak) and aspartate (strong). Since malate is formed in the next step of the CAM and C₄ cycles after PEP carboxylase catalyses the condensation of CO₂ and PEP to oxaloacetate, this works as a feedback inhibition pathway. Oxaloacetate and aspartate are easily inter-convertible through a transaminase mechanism; thus high concentrations of aspartate are also a pathway of feedback inhibition of PEP carboxylase.
The main allosteric activators of PEP carboxylase are acetyl-CoA and fructose-1,6-bisphosphate (F-1,6-BP). Both molecules are indicators of increased glycolysis levels, and thus positive feed-forward effectors of PEP carboxylase. They signal the need to produce oxaloacetate to allow more flux through the citric acid cycle. 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. It is also noteworthy that the negative effectors aspartate competes with the positive effector acetyl-CoA, suggesting that they share an allosteric binding site.
Studies have shown that energy equivalents such as AMP, ADP and ATP have no significant effect on PEP carboxylase.
The magnitudes of the allosteric effects of these different molecules on PEP carboxylase activity depend on individual organisms.
Phosphoenolpyruvate carboxylase