Anaplerotic reactions
Anaplerotic reactions, a term coined by Hans Kornberg and originating from the Greek ἀνά= 'up' and πληρόω= 'to fill', are chemical reactions that form intermediates of a metabolic pathway. Examples of such are found in the citric acid cycle (TCA cycle). In normal function of this cycle for respiration, concentrations of TCA intermediates remain constant; however, many biosynthetic reactions also use these molecules as a substrate. Anaplerosis is the act of replenishing TCA cycle intermediates that have been extracted for biosynthesis (in what are called anaplerotic reactions).
The TCA cycle is a hub of metabolism, with central importance in both energy production and biosynthesis. Therefore, it is crucial for the cell to regulate concentrations of TCA cycle metabolites in the mitochondria. Anaplerotic flux must balance cataplerotic flux in order to retain homeostasis of cellular metabolism.[1]
Reactions of anaplerotic metabolism
There are five major reactions classed as anaplerotic, and it is estimated that the production of
From | To | Reaction | Notes |
---|---|---|---|
Pyruvate |
oxaloacetate |
pyruvate + HCO3− + ATP oxaloacetate + ADP + Pi + H2O | This reaction is catalysed by mitochondria. Most important anaplerotic reaction; depending on severity, deficiency causes lactic acidosis, severe psychomotor deficiency or death in infancy [1]
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 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. Triheptanoin (fat with three heptanoic (C7:0) fatty acids) may be used to treat pyruvate carboxylase deficiency
|
adenylosuccinate | fumarate |
adenylosuccinate AMP + fumarate | This reaction is catalysed by adenylosuccinate lyase and occurs in purine synthesis and purine nucleotide cycle. Defect of this enzyme [2] causes psychomotor retardation. |
The
Diseases of anaplerotic metabolism
Pyruvate carboxylase deficiency is an inherited metabolic disorder where anaplerosis is greatly reduced. Other anaplerotic substrates such as the odd-carbon-containing triglyceride triheptanoin can be used to treat this disorder.[6]