Anaplerotic reactions, a term coined by Hans Kornberg and originating from the Gree
ἀνά 'up' an
πληρόω 'to fill', are
chemical reaction
A chemical reaction is a process that leads to the chemistry, chemical transformation of one set of chemical substances to another. When chemical reactions occur, the atoms are rearranged and the reaction is accompanied by an Gibbs free energy, ...
s that form intermediates of a
metabolic pathway
In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell (biology), cell. The reactants, products, and Metabolic intermediate, intermediates of an enzymatic reaction are known as metabolites, which are ...
. Examples of such are found in the
citric acid cycle
The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of chemical reaction, biochemical reactions that release the energy stored in nutrients through acetyl-Co ...
(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.
Reactions of anaplerotic metabolism
There are five major reactions classed as anaplerotic, and it is estimated that the production of
oxaloacetate from
pyruvate
Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell.
Pyruvic ...
has the most physiologic importance.
The
malate
Malic acid is an organic compound with the molecular formula . It is a dicarboxylic acid that is made by all living organisms, contributes to the sour taste of fruits, and is used as a food additive. Malic acid has two stereoisomeric forms ( ...
is created by
PEP carboxylase and
malate dehydrogenase in the
cytosol. Malate, in the
mitochondrial matrix, can be used to make
pyruvate
Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell.
Pyruvic ...
(catalyzed by
malic enzyme) or
oxaloacetic acid, both of which can enter the
citric acid cycle
The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of chemical reaction, biochemical reactions that release the energy stored in nutrients through acetyl-Co ...
.
Glutamine can also be used to produce oxaloacetate during anaplerotic reactions in various cell types through "glutaminolysis," which is also seen in many c-Myc transformed cells. Anaplerotic enzymes mediate an alternative pathway to
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...
secretion by aiding the production of cytosolic signal molecules.
Pancreatic β-cells, which regulate blood glucose level by secreting insulin, contain high a mounts of pyruvate carboxylase. A decrease in insulin secretion and anaplerotic activity has been found in β-cells that do not have
hypoxia-inducible factor-1 beta.
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.
References
{{DEFAULTSORT:Anaplerotic Reactions
Biochemical reactions
Cellular respiration