Propionyl-CoA
Encyclopedia
Propionyl-CoA is a coenzyme A
derivative of propionic acid
.
by propionyl-CoA carboxylase
, a biotin
-dependent enzyme also requiring bicarbonate and ATP
.
This product is converted to (R)-methylmalonyl-CoA
by methylmalonyl-CoA racemase.
(R)-Methylmalonyl-CoA
is converted to succinyl-CoA
, an intermediate in the tricarboxylic acid cycle, by methylmalonyl-CoA mutase
, an enzyme requiring cobalamin to catalyze the carbon-carbon bond migration.
The methylmalonyl-CoA mutase
mechanism begins with the cleavage of the bond between the 5' CH2- of 5'-deoxyadenosyl and the cobalt, which is in its 3+ oxidation state (III), which produces a 5'-deoxyadenosyl radical and cabalamin in the reduced Co(II) oxidation state.
Next, this radical abstracts a hydrogen atom from the methyl group of methylmalonyl-CoA, which generates a methylmalonyl-CoA radical. It is believed that this radical forms a carbon-cobalt bond to the coenzyme which is then followed by the rearrangement of the substrate's carbon skeleton, thus producing a succinyl-CoA radical. This radical then goes on to abstract a hydrogen from the previously produced 5'-deoxyadenosine, again creating a deoxyadenosyl radical, which attacks the coenzyme to reform the initial complex.
A defect in methylmalonyl-CoA mutase enzyme results in methylmalonic aciduria, a dangerous disorder that causes a lowering of blood pH.
in a very different way, similar to beta oxidation.
Not all details of this pathway have been worked out, but it appears to involve formation of acrylyl-CoA, then 3-hydroxypropionyl-CoA.
This is metabolized with loss of carbon 1 of 3-hydroxypropionyl-CoA as carbon dioxide, while carbon 3 becomes carbon 1 of acetate.
Coenzyme A
Coenzyme A 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 sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate...
derivative of propionic acid
Propionic acid
Propanoic acid is a naturally occurring carboxylic acid with chemical formula CH3CH2COOH. It is a clear liquid with a pungent odor...
.
Production
There are several different ways in which it is formed:- It is formed as a product of beta-oxidation of odd-chain fatty acidFatty acidIn 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. - It is also a product of metabolism of isoleucineIsoleucineIsoleucine is an α-amino acid with the chemical formula HO2CCHCHCH2CH3. It is an essential amino acid, which means that humans cannot synthesize it, so it must be ingested. Its codons are AUU, AUC and AUA....
and valineValineValine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
. - It is a product of alpha-ketobutyric acidAlpha-Ketobutyric acidα-Ketobutyric acid is a product of the lysis of cystathionine.It is also one of the degradation products of threonine.It can be converted to propionyl-CoA , and thus enter the citric acid cycle.- Conversion in sotolon in French Vin jaune :Vin jaune is marked by the formation of sotolon...
, which in turn is a product of digestion of threonineThreonineThreonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
and methionineMethionineMethionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
.
Metabolic fate
In mammals, propionyl-CoA is converted to (S)-methylmalonyl-CoAMethylmalonyl-CoA
Methylmalonyl-CoA is the coenzyme A linked form of methylmalonic acid. Methylmalonyl-CoA is formed from propionyl-CoA by propionyl-CoA carboxylase by help of biotin . It is converted into succinyl-CoA by methylmalonyl-CoA mutase, in a reaction that requires vitamin B12 as a cofactor...
by propionyl-CoA carboxylase
Propionyl-CoA carboxylase
Propionyl-CoA carboxylase catalyses the carboxylation reaction of propionyl CoA in the mitochondrial matrix. The enzyme is biotin dependent. The product of the reaction is -methylmalonyl CoA. Propionyl CoA is the end product of metabolism of odd-chain fatty acids, and is also a metabolite of most...
, a biotin
Biotin
Biotin, also known as Vitamin H or Coenzyme R, is a water-soluble B-complex vitamin discovered by Bateman in 1916. It is composed of a ureido ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring...
-dependent enzyme also requiring bicarbonate and ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
.
This product is converted to (R)-methylmalonyl-CoA
Methylmalonyl-CoA
Methylmalonyl-CoA is the coenzyme A linked form of methylmalonic acid. Methylmalonyl-CoA is formed from propionyl-CoA by propionyl-CoA carboxylase by help of biotin . It is converted into succinyl-CoA by methylmalonyl-CoA mutase, in a reaction that requires vitamin B12 as a cofactor...
by methylmalonyl-CoA racemase.
(R)-Methylmalonyl-CoA
Methylmalonyl-CoA
Methylmalonyl-CoA is the coenzyme A linked form of methylmalonic acid. Methylmalonyl-CoA is formed from propionyl-CoA by propionyl-CoA carboxylase by help of biotin . It is converted into succinyl-CoA by methylmalonyl-CoA mutase, in a reaction that requires vitamin B12 as a cofactor...
is converted to 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...
, an intermediate in the tricarboxylic acid cycle, by 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...
, an enzyme requiring cobalamin to catalyze the carbon-carbon bond migration.
The 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...
mechanism begins with the cleavage of the bond between the 5' CH2- of 5'-deoxyadenosyl and the cobalt, which is in its 3+ oxidation state (III), which produces a 5'-deoxyadenosyl radical and cabalamin in the reduced Co(II) oxidation state.
Next, this radical abstracts a hydrogen atom from the methyl group of methylmalonyl-CoA, which generates a methylmalonyl-CoA radical. It is believed that this radical forms a carbon-cobalt bond to the coenzyme which is then followed by the rearrangement of the substrate's carbon skeleton, thus producing a succinyl-CoA radical. This radical then goes on to abstract a hydrogen from the previously produced 5'-deoxyadenosine, again creating a deoxyadenosyl radical, which attacks the coenzyme to reform the initial complex.
A defect in methylmalonyl-CoA mutase enzyme results in methylmalonic aciduria, a dangerous disorder that causes a lowering of blood pH.
Metabolism in plants and insects
In plants and insects propionyl-CoA is metabolized to acetateAcetate
An acetate is a derivative of acetic acid. This term includes salts and esters, as well as the anion found in solution. Most of the approximately 5 billion kilograms of acetic acid produced annually in industry are used in the production of acetates, which usually take the form of polymers. In...
in a very different way, similar to beta oxidation.
Not all details of this pathway have been worked out, but it appears to involve formation of acrylyl-CoA, then 3-hydroxypropionyl-CoA.
This is metabolized with loss of carbon 1 of 3-hydroxypropionyl-CoA as carbon dioxide, while carbon 3 becomes carbon 1 of acetate.