Anaplerotic reactions are those that form intermediates of a metabolic pathway. Examples of such are found in the Tricarboxylic acid (TCA) Cycle (also called the Krebs or citric acid cycle

Citric acid cycle

The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...

). 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 cataplerotic 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 4 major reactions classed as anaplerotic, yet the production of oxaloacetate from pyruvate has, it is estimated, the most physiologic importance.

From

To

Reaction

Notes >- | Pyruvate

oxaloacetate

pyruvate + HCO3- + ATP oxaloacetate + ADP + Pi + H2O

pyruvate carboxylase Pyruvate carboxylase Pyruvate carboxylase is an enzyme of the ligase class that catalyzes the irreversible carboxylation of pyruvate to form oxaloacetate .It is an important anaplerotic reaction that creates oxaloacetate from pyruvate... , an enzyme Enzyme Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...  activated by Acetyl-CoA, indicating a lack of oxaloacetate. It occurs in animal mitochondria. Pyruvate can also be converted to L-malate Malic acid Malic acid is an organic compound with the formula HO2CCH2CHOHCO2H. It is a dicarboxylic acid which is made by all living organisms, contributes to the pleasantly sour taste of fruits, and is used as a food additive. Malic acid has two stereoisomeric forms , though only the L-isomer exists... , another intermediate, in a similar way. >- | Aspartate

oxaloacetate

-

transamination Transamination There are two chemical reactions known as transamination . The first is the reaction between an amino acid and an alpha-keto acid...  reaction, via aspartate transaminase Aspartate transaminase Aspartate transaminase , also called aspartate aminotransferase or serum glutamic oxaloacetic transaminase , is a pyridoxal phosphate -dependent transaminase enzyme . AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in... . >- | Glutamate

α-ketoglutarate

glutamate + NAD+ + H2O NH4+ + α-ketoglutarate + NADH + H+.

>- | β-Oxidation of fatty acid Fatty acid In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from... s

succinyl-CoA Succinyl-CoA Succinyl-Coenzyme A, abbreviated as Succinyl-CoA or SucCoA, is a combination of succinic acid and coenzyme A.-Source:It is an important intermediate in the citric acid cycle, where it is synthesized from α-Ketoglutarate by α-ketoglutarate dehydrogenase through decarboxylation...

-

When odd-chain fatty acids are oxidized, one molecule of succinyl-CoA is formed per fatty acid. The final enzyme is methylmalonyl-CoA mutase Methylmalonyl-CoA mutase Methylmalonyl Coenzyme A mutase, also known as MCM is an enzyme that catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA and it is involved in key metabolic pathways... .

The malate

Malate

Malate is the ionized form of malic acid. It is an important chemical compound in biochemistry. In the C4 carbon fixation process, malate is a source of CO2 in the Calvin cycle....

 is created by PEP carboxylase and malate dehydrogenase

Malate dehydrogenase

Malate dehydrogenase is an enzyme in the citric acid cycle that catalyzes the conversion of malate into oxaloacetate and vice versa...

 in the cytosol

Cytosol

The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

. Malate, in the mitochondrial matrix

Mitochondrial matrix

In the mitochondrion, the matrix contains soluble enzymes that catalyze the oxidation of pyruvate and other small organic molecules.The mitochondrial matrix also contains the mitochondria's DNA and ribosomes. The word "matrix" stems from the fact that this space is viscous, compared to the...

, can be used to make pyruvate (catalyzed by malic enzyme

Malate dehydrogenase (decarboxylating)

Malic enzyme , not to be confused with malate dehydrogenase , is an enzyme that catalyzes the chemical reaction-malate + NADP+ \rightleftharpoons pyruvate + CO2 + NADPH...

) or oxaloacetic acid

Oxaloacetic acid

Oxaloacetic acid is an organic compound with the chemical formula C4H4O5 or HOOC---COOH. It also has other names ....

, both of which can enter the citric acid cycle

Citric acid cycle

The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...

.

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

Triheptanoin

Triheptanoin is triglyceride that is composed of three seven-carbon fatty acids. These odd-carbon fatty acids are able to provide anaplerotic substrates for the TCA cycle. Triheptanoin is used clinically in humans to treat inherited metabolic diseases, such as pyruvate carboxylase deficiency and...

can be used to treat this disorder.