Propionyl-CoA

Propionyl-CoA
IUPAC name S-[2-[3-[[4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethyl] propanethioate
Other names Propionyl Coenzyme A; Propanoyl Coenzyme A
Identifiers
CAS number	N
PubChem
ChemSpider	Y
MeSH
Jmol-3D images	Image 1
SMILES CCC(=O)SCCNC(=O)CCNC(=O)C(O)C(C)(C)COP(O)(=O)OP(O)(=O)OCC3OC(n2cnc1c(N)ncnc12)[C@H](O)[C@@H]3OP(O)(O)=O
InChI InChI=1S/C24H40N7O17P3S/c1-4-15(33)52-8-7-26-14(32)5-6-27-22(36)19(35)24(2,3)10-45-51(42,43)48-50(40,41)44-9-13-18(47-49(37,38)39)17(34)23(46-13)31-12-30-16-20(25)28-11-29-21(16)31/h11-13,17-19,23,34-35H,4-10H2,1-3H3,(H,26,32)(H,27,36)(H,40,41)(H,42,43)(H2,25,28,29)(H2,37,38,39)/t13?,17-,18-,19?,23?/m1/s1 Y Key: QAQREVBBADEHPA-HOMDEXLGSA-N Y InChI=1/C24H40N7O17P3S/c1-4-15(33)52-8-7-26-14(32)5-6-27-22(36)19(35)24(2,3)10-45-51(42,43)48-50(40,41)44-9-13-18(47-49(37,38)39)17(34)23(46-13)31-12-30-16-20(25)28-11-29-21(16)31/h11-13,17-19,23,34-35H,4-10H2,1-3H3,(H,26,32)(H,27,36)(H,40,41)(H,42,43)(H2,25,28,29)(H2,37,38,39)/t13?,17-,18-,19?,23?/m1/s1 Key: QAQREVBBADEHPA-HOMDEXLGBF
Properties
Molecular formula	C24H40N7O17P3S
Molar mass	823.60 g/mol
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
N   Y/N?)

Propionyl-CoA is a coenzyme A derivative of propionic acid.

Metabolism in animals

Production

There are several different ways in which it is formed:

• It is formed as a product of beta-oxidation of odd-chain fatty acids.
• It is also a product of metabolism of isoleucine and valine.
• It is a product of alpha-ketobutyric acid, which in turn is a product of digestion of threonine and methionine.
• It is formed as a by-product during the conversion of cholesterol to bile acids

Metabolic fate

In mammals, propionyl-CoA is converted to (S)-methylmalonyl-CoA 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.

Metabolism in plants and insects

In plants and insects propionyl-CoA is metabolized to acetate 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.

References

• Halarnkar P, Blomquist G (1989). "Comparative aspects of propionate metabolism". Comp. Biochem. Physiol., B 92 (2): 227–31.