Adenosylcobalamin

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Adenosylcobalamin
AdoCbl-ColorCoded.png
Cobamamide 3D sticks.png
Clinical data
AHFS/Drugs.com International Drug Names
Routes of
administration 		Oral
ATC code
Legal status
Legal status
Identifiers
  • Coα-[α-(5,6-dimethylbenzimidazolyl)]-Coβ-
    (5'-deoxy-5'-adenosyl)cobamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard 100.034.192 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C72H100CoN18O17P
Molar mass 1579.608 g·mol−1
  • InChI=1S/C62H90N13O14P.C10H12N5O3.Co/c1-29-20-39-40(21-30(29)2)75(28-70-39)57-52(84)53(41(27-76)87-57)89-90(85,86)88-31(3)26-69-49(83)18-19-59(8)37(22-46(66)80)56-62(11)61(10,25-48(68)82)36(14-17-45(65)79)51(74-62)33(5)55-60(9,24-47(67)81)34(12-15-43(63)77)38(71-55)23-42-58(6,7)35(13-16-44(64)78)50(72-42)32(4)54(59)73-56;1-4-6(16)7(17)10(18-4)15-3-14-5-8(11)12-2-13-9(5)15;/h20-21,23,28,31,34-37,41,52-53,56-57,76,84H,12-19,22,24-27H2,1-11H3,(H15,63,64,65,66,67,68,69,71,72,73,74,77,78,79,80,81,82,83,85,86);2-4,6-7,10,16-17H,1H2,(H2,11,12,13);/q;;+2/p-2/t31?,34?,35?,36?,37?,41-,52-,53-,56?,57+,59?,60?,61?,62?;4-,6-,7-,10-;/m11./s1 Yes check.svgY
  • Key:ZIHHMGTYZOSFRC-CXGXMSGESA-L Yes check.svgY
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Adenosylcobalamin (AdoCbl), also known as coenzyme B12, cobamamide, and dibencozide, is, along with methylcobalamin (MeCbl), one of the biologically active forms of vitamin B12. [1]

Contents

Adenosylcobalamin participates as a cofactor in radical-mediated 1,2-carbon skeleton rearrangements. These processes require the formation of the deoxyadenosyl radical through homolytic dissociation of the carbon-cobalt bond. This bond is exceptionally weak, with a bond dissociation energy of 31 kcal/mol, which is further lowered in the chemical environment of an enzyme active site. [2] An enzyme that uses adenosylcobalamin as a cofactor is methylmalonyl-CoA mutase (MCM).

Further experimentation has also determined adenosylcobalamin's role in regulating expression of some bacterial genes. By binding to CarH,[ clarification needed ] AdoCbl can modulate carotenoid genes, which confer warm colors onto various plants. Carotenoid transcription is activated by sunlight, due to the response from AdoCbl. [3] There are other photoreceptors across different bacterial communities, aside from CarH, that also have reactive capability when bound to AdoCbl. For instance, AerR is another factor that uses AdoCbl to give off purple pigmentation. Additional examination of adenosylcobalamin-bound enzymes and the development of this cofactor over time may prove to hold regulatory function of DNA and RNA. [4]

See also

Related Research Articles

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<span class="mw-page-title-main">MMACHC</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">MMADHC</span> Protein-coding gene in humans

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<span class="mw-page-title-main">Vitamin B12-binding domain</span> Type of protein domain

In molecular biology, the vitamin B12-binding domain is a protein domain which binds to cobalamin. It can bind two different forms of the cobalamin cofactor, with cobalt bonded either to a methyl group (methylcobalamin) or to 5'-deoxyadenosine (adenosylcobalamin). Cobalamin-binding domains are mainly found in two families of enzymes present in animals and prokaryotes, which perform distinct kinds of reactions at the cobalt-carbon bond. Enzymes that require methylcobalamin carry out methyl transfer reactions. Enzymes that require adenosylcobalamin catalyse reactions in which the first step is the cleavage of adenosylcobalamin to form cob(II)alamin and the 5'-deoxyadenosyl radical, and thus act as radical generators. In both types of enzymes the B12-binding domain uses a histidine to bind the cobalt atom of cobalamin cofactors. This histidine is embedded in a DXHXXG sequence, the most conserved primary sequence motif of the domain. Proteins containing the cobalamin-binding domain include:

<span class="mw-page-title-main">Cob(I)yrinic acid a,c-diamide adenosyltransferase</span> Class of enzymes

In molecular biology, cob(I)yrinic acid a,c-diamide adenosyltransferase EC 2.5.1.17 is an enzyme which catalyses the conversion of cobalamin into one of its coenzyme forms, adenosylcobalamin. Adenosylcobalamin is required as a cofactor for the activity of certain enzymes. AdoCbl contains an adenosyl moiety liganded to the cobalt ion of cobalamin via a covalent Co-C bond.

<span class="mw-page-title-main">Cobalamin biosynthesis</span>

Cobalamin biosynthesis is the process by which bacteria and archea make cobalamin, vitamin B12. Many steps are involved in converting aminolevulinic acid via uroporphyrinogen III and adenosylcobyric acid to the final forms in which it is used by enzymes in both the producing organisms and other species, including humans who acquire it through their diet.

Radical SAMenzymes is a superfamily of enzymes that use a [4Fe-4S]+ cluster to reductively cleave S-adenosyl-L-methionine (SAM) to generate a radical, usually a 5′-deoxyadenosyl radical (5'-dAdo), as a critical intermediate. These enzymes utilize this radical intermediate to perform diverse transformations, often to functionalize unactivated C-H bonds. Radical SAM enzymes are involved in cofactor biosynthesis, enzyme activation, peptide modification, post-transcriptional and post-translational modifications, metalloprotein cluster formation, tRNA modification, lipid metabolism, biosynthesis of antibiotics and natural products etc. The vast majority of known radical SAM enzymes belong to the radical SAM superfamily, and have a cysteine-rich motif that matches or resembles CxxxCxxC. Radical SAM enzymes comprise the largest superfamily of metal-containing enzymes.

References

  1. ↑ Marsh EN, Meléndez GD (November 2012). "Adenosylcobalamin enzymes: theory and experiment begin to converge". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1824 (11): 1154–1164. doi:10.1016/j.bbapap.2012.03.012. PMC   3580769 . PMID   22516318.
  2. ↑ Kräutler B, Arigoni D, Golding BT (1998). Vitamin B12 and B12-proteins : lectures presented at the 4th European Symposium on Vitamin B12 and B12-Proteins. Weinheim: Wiley-VCH. ISBN   9783527612192. OCLC   212131311.
  3. ↑ Jost M (April 1, 2015). "An Old Cofactor in a New Light: Adenosylcobalamin in Light-Dependent Gene Regulation". The FASEB Journal. 29. doi: 10.1096/fasebj.29.1_supplement.573.25 . S2CID   89044509.
  4. ↑ Chemaly SM (October 2016). "New light on vitamin B12: The adenosylcobalamin-dependent photoreceptor protein CarH". South African Journal of Science. 112 (9–10): 9. doi: 10.17159/sajs.2016/20160106 . S2CID   90441731.
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