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anaplerotic

Anaplerotic reactions

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.

pyruvate carboxylase deficiency is an inherited metabolic disorder where anaplerosis is greatly reduced. Other anaplerortic substrates such as the odd-carbon containing triglyceride Triheptanoin is used to treat this disorder.

There are 4 reactions classed as anaplerotic, yet the production of oxaloacetate from pyruvate has probably the most physiologic importance.

From To Reaction Notes
Pyruvate oxaloacetate pyruvate + CO2 + H2O + ATP longrightarrow 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 longrightarrow 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.

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