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 IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
s that form intermediates of a
metabolic pathway
In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reac ...
. Examples of such are found in the
citric acid cycle
The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins ...
(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
Oxaloacetic acid (also known as oxalacetic acid or OAA) is a crystalline organic compound with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes ...
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 aci ...
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 (L ...
is created by
PEP carboxylase PEP carboxylase may refer to:
* Phosphoenolpyruvate carboxylase
Phosphoenolpyruvate carboxylase (also known as PEP carboxylase, PEPCase, or PEPC; , PDB ID: 3ZGE) is an enzyme in the family of carboxy-lyases found in plants and some bacteria that ...
and
malate dehydrogenase
Malate dehydrogenase () (MDH) is an enzyme that reversibly catalyzes the oxidation of malate to oxaloacetate using the reduction of NAD+ to NADH. This reaction is part of many metabolic pathways, including the citric acid cycle. Other malate ...
in the
cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
. Malate, in the
mitochondrial matrix
In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribo ...
, 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 aci ...
(catalyzed by
malic enzyme
Malic enzyme may refer to '' decarboxylating'' malate dehydrogenases:
* Malate dehydrogenase (decarboxylating) () or NAD-malic enzyme
* Malate dehydrogenase (oxaloacetate-decarboxylating) (), another NAD-malic enzyme
* Malate dehydrogenase (oxalo ...
) or
oxaloacetic acid
Oxaloacetic acid (also known as oxalacetic acid or OAA) is a crystalline organic compound with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes ...
, both of which can enter the
citric acid cycle
The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins ...
.
Glutamine
Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, ...
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 ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
secretion by aiding the production of cytosolic signal molecules.
Pancreatic β-cell
Beta cells (β-cells) are a type of cell (biology), cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and fun ...
s 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
Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia. They are only present in parahoxozoan animals.
Discovery
The HIF transcriptional complex wa ...
-1 beta
Diseases of anaplerotic metabolism
Pyruvate carboxylase deficiency
Pyruvate carboxylase deficiency is an inherited disorder that causes lactic acid to accumulate in the blood. High levels of these substances can damage the body's organs and tissues, particularly in the nervous system. Pyruvate carboxylase defici ...
is an inherited metabolic disorder where anaplerosis is greatly reduced. Other anaplerotic substrates such as the odd-carbon-containing triglyceride
triheptanoin
Triheptanoin, sold under the brand name Dojolvi, is a medication for the treatment of children and adults with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD).
The most common adverse reactions include abdominal pain, d ...
can be used to treat this disorder.
References
{{DEFAULTSORT:Anaplerotic Reactions
Cellular respiration