Methylmalonyl-CoA

Source: Wikipedia, the free encyclopedia.
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
3D model (
JSmol
)
ChEBI
ChemSpider
IUPHAR/BPS
  • 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
  • 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
C25H40N7O19P3S
Molar mass 867.608 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Methylmalonyl-CoA is the thioester consisting of coenzyme A linked to methylmalonic acid. It is an important intermediate in the biosynthesis of succinyl-CoA, which plays an essential role in the tricarboxylic acid cycle (aka the Citric Acid Cycle, or Krebs Cycle).[1] The compound is sometimes referred to as "methylmalyl-CoA".[2]

Biosynthesis and metabolism

Illustration of the role of Methylmalonyl-CoA in the Citric Acid Cycle.[3]

Methylmalonyl-CoA results from the metabolism of fatty acid with an odd number of carbons, of amino acids valine, isoleucine, methionine, threonine or of cholesterol side-chains, forming Propionyl-CoA.[4] The latter is also formed from propionic acid, which bacteria produce in the intestine.[4] Propionyl-CoA and bicarbonate are converted to Methylmalonyl-CoA by the enzyme propionyl-CoA Carboxylase.[1] It then is converted into succinyl-CoA by methylmalonyl-CoA mutase (MUT). This reaction is a reversible isomerization. In this way, the compound enters the Citric Acid Cycle. The following diagram demonstrates the aforementioned reaction:[2]

Propionyl CoA + Bicarbonate → Methylmalonyl CoA → Succinyl CoA

Vitamin B12

radical reaction.[5]

Illustration of the reaction where Methylmalonyl-CoA is transformed into Succinyl-CoA by Methylmalonyl-CoA mutase (MUT).[5]

Related diseases

Methylmalonic Acidemia (MMA)

Main article: Methylmalonyl-CoA mutase deficiency

This disease occurs when methylmalonyl-CoA mutase is unable to isomerize sufficient amounts of methylmalonyl-CoA into succinyl-CoA.[6] This causes a buildup of propionic and/or methylmalonic acid, which has effects on infants ranging from severe brain damage to death.[4] The disease is linked to Vitamin B12, which is the metabolic precursor to methylmalonyl-CoA mutase.[6][3]

Combined malonic and methylmalonic aciduria (CMAMMA)

In the metabolic disease combined malonic and methylmalonic aciduria (CMAMMA) due to ACSF3 deficiency, methylmalonyl-CoA synthetase is reduced, which converts toxic methylmalonic acid to methylmalonyl-CoA and thus supplies it to the citrate cycle.[7][8] The result is an accumulation of methylmalonic acid.

References

  1. ^
    PMID 29033250
    .
  2. ^
    ISBN 0-7167-4339-6
    .
  3. ^
    PMID 30693532
    .
  4. ^
    PMID 25205257
    .
  5. ^
    PMID 22116707. {{cite book}}: |work= ignored (help
    )
  6. ^
    PMID 22661206
    .
  7. PMID 33625768
    .
  8. PMID 30201289
    .
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