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Methylmalonyl-CoA is the
thioester In organic chemistry, thioesters are organosulfur compounds with the functional group . They are analogous to carboxylate esters () with the sulfur in the thioester playing the role of the linking oxygen in the carboxylate ester, as implied by t ...
consisting of
coenzyme A Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a subs ...
linked to
methylmalonic acid Methylmalonic acid (MMA) (conjugate base methylmalonate) is a dicarboxylic acid that is a ''C''-methylated derivative of malonate. The coenzyme A linked form of methylmalonic acid, methylmalonyl-CoA, is converted into succinyl-CoA by methylmalonyl ...
. It is an important intermediate in the
biosynthesis Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...
of
succinyl-CoA Succinyl-coenzyme A, abbreviated as succinyl-CoA () or SucCoA, is a thioester of succinic acid and coenzyme A. Sources It is an important intermediate in the citric acid cycle, where it is synthesized from α-ketoglutarate by α-ketoglutarate de ...
, which plays an essential role in the tricarboxylic acid cycle (aka the Citric Acid Cycle, or Krebs Cycle). The compound is sometimes referred to as "methylmalyl-CoA".


Biosynthesis and metabolism

Methylmalonyl-CoA results from the
metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
of
fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...
with an
odd number In mathematics, parity is the property of an integer of whether it is even or odd. An integer is even if it is a multiple of two, and odd if it is not.. For example, −4, 0, 82 are even because \begin -2 \cdot 2 &= -4 \\ 0 \cdot 2 &= 0 \\ 41 ...
of
carbons Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon makes u ...
or from cholesterol side-chains, forming
Propionyl-CoA Propionyl-CoA is a coenzyme A derivative of propionic acid. It is composed of a 24 total carbon chain (without the coenzyme, it is a 3 carbon structure) and its production and metabolic fate depend on which organism it is present in. Several diffe ...
. Propionyl-CoA and
bicarbonate In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula . Bicarbonate serves a crucial biochemic ...
are converted to Methylmalonyl-CoA by the enzyme
propionyl-CoA Carboxylase Propionyl-CoA carboxylase (, PCC) catalyses the carboxylation reaction of propionyl-CoA in the mitochondrial matrix. PCC has been classified both as a ligase and a lyase. The enzyme is biotin-dependent. The product of the reaction is (S)-methylmal ...
. It then is converted into succinyl-CoA by
methylmalonyl-CoA mutase Methylmalonyl-CoA mutase (, MCM), mitochondrial, also known as methylmalonyl-CoA isomerase, is a protein that in humans is encoded by the ''MUT'' gene. This vitamin B12-dependent enzyme catalyzes the isomerization of methylmalonyl-CoA to succiny ...
(MUT). This reaction is a reversible
isomerization In chemistry, isomerization or isomerisation is the process in which a molecule, polyatomic ion or molecular fragment is transformed into an isomer with a different chemical structure. Enolization is an example of isomerization, as is tautomeriz ...
. In this way, the compound enters the Citric Acid Cycle. The following diagram demonstrates the aforementioned reaction: Propionyl CoA + Bicarbonate → Methylmalonyl CoA → Succinyl CoA


Vitamin B12

Vitamin B12 plays an integral role in this reaction. Coenzyme B12 ( adenosyl-cobalamin) is an
organometallic Organometallic chemistry is the study of organometallic compounds, chemical compounds containing at least one chemical bond between a carbon atom of an organic molecule and a metal, including alkali, alkaline earth, and transition metals, and so ...
form of Vitamin B12 and serves as the cofactor of Methylmalonyl-CoA mutase, which is an essential
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
in the human body. The transformation of Methylmalonyl-CoA to Succinyl-CoA by this enzyme is a
radical reaction In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired electron, unpaired valence electron. With some exceptions, these unpaired electrons make radicals highly chemical reaction, chemi ...
.


Related diseases


Methylmalonic Acidemia (MMA)

This disease occurs when methylmalonyl-CoA mutase is unable to isomerize sufficient amounts of methylmalonyl-CoA into succinyl-CoA. This causes a buildup of propionic and/or methylmalonic acid, which has effects on infants ranging from severe brain damage to death. The disease is linked to Vitamin B12, which is the metabolic precursor to methylmalonyl-CoA mutase.


References

Thioesters of coenzyme A {{Microbiology-stub