Anaplerotic reactions

Overview

Anaplerotic reactions are those that form intermediates of the TCA or citric acid cycle. The malate is created by PEP carboxylase and malate dehydrogenase in the cytosol. Malate, in the mitochondrial matrix, can be used to make pyruvate (catalyzed by NAD+ malic enzyme) or oxaloacetic acid, both of which can enter the citric acid cycle. As this is a cycle, formation of any of the intermediates can be used to ‘top up’ the whole cycle. Anaplerotic is of Greek origin, meaning “to fill up”.

There are 4 reactions classed as anaplerotic, although the production of oxaloacetate from pyruvate is probably the most important physiologically.

From	To	Reaction	Notes
Pyruvate	oxaloacetate	pyruvate + CO₂ + H₂O + ATP <math>\longrightarrow</math> oxaloacetate + ADP + Pi + 2H⁺	This reaction is catalysed by pyruvate carboxylase, an enzyme activated by Acetyl-CoA, indicating a lack of oxaloacetate. Pyruvate can also be converted to L-malate, another intermediate, in a similar way.
Aspartate	oxaloacetate	–	This is a reversible reaction forming oxaloacetate from aspartate in a transamination reaction, via aspartate transaminase.
Glutamate	α-ketoglutarate	glutamate + NAD⁺ + H₂O <math>\longrightarrow</math> NH₄⁺ + α-ketoglutarate + NADH + H⁺.	This reaction is catalysed by glutamate-dehydrogenase.
β-oxidation of fatty acids	succinyl-CoA	–	When odd-chain fatty acids are oxidized, one molecule of succinyl-CoA is formed per fatty acid. The final enzyme is methylmalonyl-CoA mutase.