Methylmalonyl-CoA is thethioester consisting ofcoenzyme A linked tomethylmalonic acid. It is an important intermediate in thebiosynthesis ofsuccinyl-CoA, which plays an essential role in the tricarboxylic acid cycle (aka theCitric Acid Cycle, or Krebs Cycle).^[1]

Methylmalonyl-CoA

Names
Systematic IUPAC name (9R)-1-[(2R,3S,4R,5R)-5-(6-Amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)oxolan-2-yl]-3,5,9-trihydroxy-8,8,20-trimethyl-3,5,10,14,19-pentaoxo-2,4,6-trioxa-18-thia-11,15-diaza-3λ5,5λ5-diphosphahenicosan-21-oic acid
Identifiers
CAS Number	1264-45-5 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:16625 N
ChemSpider	110440 N
IUPHAR/BPS	5223
PubChemCID	123909
CompTox Dashboard(EPA)	DTXSID20925529
InChI InChI=1S/C25H40N7O19P3S/c1-12(23(37)38)24(39)55-7-6-27-14(33)4-5-28-21(36)18(35)25(2,3)9-48-54(45,46)51-53(43,44)47-8-13-17(50-52(40,41)42)16(34)22(49-13)32-11-31-15-19(26)29-10-30-20(15)32/h10-13,16-18,22,34-35H,4-9H2,1-3H3,(H,27,33)(H,28,36)(H,37,38)(H,43,44)(H,45,46)(H2,26,29,30)(H2,40,41,42)/t12?,13-,16-,17-,18+,22-/m1/s1 N Key: MZFOKIKEPGUZEN-FBMOWMAESA-N N InChI=1/C25H40N7O19P3S/c1-12(23(37)38)24(39)55-7-6-27-14(33)4-5-28-21(36)18(35)25(2,3)9-48-54(45,46)51-53(43,44)47-8-13-17(50-52(40,41)42)16(34)22(49-13)32-11-31-15-19(26)29-10-30-20(15)32/h10-13,16-18,22,34-35H,4-9H2,1-3H3,(H,27,33)(H,28,36)(H,37,38)(H,43,44)(H,45,46)(H2,26,29,30)(H2,40,41,42)/t12?,13-,16-,17-,18+,22-/m1/s1 Key: MZFOKIKEPGUZEN-FBMOWMAEBZ
SMILES CC(C(=O)O)C(=O)SCCNC(=O)CCNC(=O)[C@@H](C(C)(C)COP(=O)(O)OP(=O)(O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N2C=NC3=C(N=CN=C32)N)O)OP(=O)(O)O)O
Properties
Chemical formula	C25H40N7O19P3S
Molar mass	867.608 g/mol
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

Methylmalonyl-CoA results from themetabolism offatty acid with anodd number ofcarbons, ofamino acidsvaline,isoleucine,methionine,threonine or ofcholesterol side-chains, formingPropionyl-CoA.^[2] The latter is also formed frompropionic acid, which bacteria produce in the intestine.^[2] Propionyl-CoA andbicarbonate are converted to Methylmalonyl-CoA by the enzymepropionyl-CoA Carboxylase.^[1] It then is converted into succinyl-CoA bymethylmalonyl-CoA mutase (MUT). This reaction is areversibleisomerization. In this way, the compound enters the Citric Acid Cycle. The following diagram demonstrates the aforementioned reaction:^[3]

Propionyl CoA + Bicarbonate→ Methylmalonyl CoA→ Succinyl CoA

Vitamin B₁₂ plays an integral role in this reaction. Coenzyme B₁₂ (adenosyl-cobalamin) is anorganometallic form ofVitamin B₁₂ and serves as thecofactor of Methylmalonyl-CoA mutase, which is an essentialenzyme in the human body.^[4] The transformation of Methylmalonyl-CoA to Succinyl-CoA by this enzyme is aradical reaction.^[4]

This disease occurs when methylmalonyl-CoA mutase is unable to isomerize sufficient amounts of methylmalonyl-CoA into succinyl-CoA.^[5] This causes a buildup of propionic and/or methylmalonic acid, which has effects on infants ranging from severe brain damage to death.^[2] The disease is linked to Vitamin B₁₂, which is a cofactor for the enzyme methylmalonyl-CoA mutase.^[5][6]

In the metabolic diseasecombined malonic and methylmalonic aciduria (CMAMMA),acyl-CoA synthetase family member 3 (ACSF3) is reduced, which converts toxic methylmalonic acid to methylmalonyl-CoA and thus supplies it to the citric acid cycle.^[7][8] The result is an accumulation of methylmalonic acid.