L-methylmalonyl-CoA
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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 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 methylmalon ...
. It is an important intermediate in the biosynthesis 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 d ...
, 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 c ...
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, ...
with an odd number of carbons 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 biochem ...
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 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 ...
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 valence electron. With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spon ...
.


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