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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2006-05-22 14:17:47 UTC
Update Date2018-05-04 22:19:25 UTC
HMDB IDHMDB0002308
Secondary Accession Numbers
  • HMDB0014345
  • HMDB02308
  • HMDB14345
Metabolite Identification
Common NameHydroxocobalamin
DescriptionHydroxocobalamin, also known as hydroxycobalamin, is a member of the class of compounds known as cobalamin derivatives. These organic compounds contain a corrin ring, a cobalt atom, and a nucleotide moiety. Cobalamin derivatives are actually derived from vitamin B12. Hydroxocobalamin is practically insoluble (in water) and a moderately acidic compound (based on its pKa). Hydroxocobalamin is formally rated as a possibly carcinogenic (IARC 2B) potentially toxic compound. Hydroxocobalamin is a drug used in the treatment of pernicious anemia and in the prevention and treatment of vitamin B12 deficiency arising from alcoholism, malabsorption, tapeworm infestation, celiac disease, hyperthyroidism, hepatic-biliary tract disease, persistent diarrhea, ileal resection, pancreatic cancer, renal disease, prolonged stress, vegan diets, macrobiotic diets, and other restrictive diets. Hydroxocobalamin is also used in the treatment of known or suspected cyanide poisoning. Hydroxocobalamin was first isolated in 1949. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Hydroxocobalamin is available as a generic medication. The wholesale cost in the developing world is about 0.12 to 0.84 USD per dose. Commercially, it is made from one of a number of different types of bacteria (Wikipedia). Primarily hepatic. cobalamins are absorbed in the ileum and stored in the liver. They continuously undergo enterohepatic recycling via secretion in the bile. Part of the dose is excreted in the urine, most of it in the first 8 hours (DrugBank). Cobalt inhalation can cause asthma-like breathing problems. Skin contact is known to result in contact dermatitis, which is characterized by irritation and rashes. Ingesting large amounts of cobalt may cause nausea and vomiting (L2090) (T3DB). Hydroxocobalamin is only found in individuals that have used or taken this drug.
Structure
Thumb
Synonyms
ValueSource
HydroxycobalaminChEBI
OH-CBLChEBI
Vitamin b-12bChEBI
HydroxominHMDB
Hydroxo-cobalaminHMDB
a-(5,6-Dimethylbenzimidazolyl)hydroxocobamideHMDB
alpha CobioneHMDB
alpha-(5,6-Dimethylbenzimidazolyl)hydroxocobamideHMDB
AxlonHMDB
Ciplamin HHMDB
CobalexHMDB
Cobalin HHMDB
Cobinamide hydroxide phosphate 3'-ester with 5,6-dimethyl-1-a-D-ribofuranosylbenzimidazole inner saltHMDB
Cobinamide hydroxide phosphate 3'-ester with 5,6-dimethyl-1-alpha-delta-ribofuranosylbenzimidazole inner saltHMDB
CodroxominHMDB
DocclanHMDB
DocelanHMDB
DocevitaHMDB
DroxominHMDB
Ducobee hyHMDB
DuradoceHMDB
Duralta-12HMDB
HydrocobalaminHMDB
HydrogrisevitHMDB
HydrovitHMDB
HydroxocobalamineHMDB
HydroxocobalaminHMDB
Chemical FormulaC62H89CoN13O15P
Average Molecular Weight1346.3551
Monoisotopic Molecular Weight1345.567070949
IUPAC Name(10S,12R,13S,17R,23R,24R,25R,30S,35S,36S,40S,41S,42R,46R)-30,35,40-tris(2-carbamoylethyl)-24,36,41-tris(carbamoylmethyl)-1,46-dihydroxy-12-(hydroxymethyl)-5,6,17,23,28,31,31,36,38,41,42-undecamethyl-15,20-dioxo-11,14,16-trioxa-2lambda5,9,19,26,43lambda5,44lambda5,45lambda5-heptaaza-15lambda5-phospha-1-cobaltadodecacyclo[27.14.1.1^{1,34}.1^{2,9}.1^{10,13}.0^{1,26}.0^{3,8}.0^{23,27}.0^{25,42}.0^{32,44}.0^{39,43}.0^{37,45}]heptatetraconta-2(47),3,5,7,27,29(44),32,34(45),37,39(43)-decaene-2,43,44,45-tetrakis(ylium)-1,1,1-triuid-15-olate
Traditional Name(10S,12R,13S,17R,23R,24R,25R,30S,35S,36S,40S,41S,42R,46R)-30,35,40-tris(2-carbamoylethyl)-24,36,41-tris(carbamoylmethyl)-1,46-dihydroxy-12-(hydroxymethyl)-5,6,17,23,28,31,31,36,38,41,42-undecamethyl-15,20-dioxo-11,14,16-trioxa-2lambda5,9,19,26,43lambda5,44lambda5,45lambda5-heptaaza-15lambda5-phospha-1-cobaltadodecacyclo[27.14.1.1^{1,34}.1^{2,9}.1^{10,13}.0^{1,26}.0^{3,8}.0^{23,27}.0^{25,42}.0^{32,44}.0^{39,43}.0^{37,45}]heptatetraconta-2(47),3,5,7,27,29(44),32,34(45),37,39(43)-decaene-2,43,44,45-tetrakis(ylium)-1,1,1-triuid-15-olate
CAS Registry Number13422-51-0
SMILES
[N+]1=2[Co-3]345([N+]6=C7[C@H]([C@@](CC(=O)N)(C)[C@@]6([C@@]6(N3C(=C(C)C3=[N+]4C(C(C)(C)[C@@H]3CCC(=O)N)=CC3=[N+]5C(=C7C)[C@@](CC(=O)N)([C@@H]3CCC(=O)N)C)[C@@](C)([C@H]6CC(=O)N)CCC(NC[C@@H](C)OP(=O)(O[C@@H]3[C@H](O[C@H](N(C4=CC(=C(C=C14)C)C)C=2)[C@@H]3O)CO)[O-])=O)[H])C)CCC(=O)N)O[H]
InChI Identifier
InChI=1S/C62H90N13O14P.Co.H2O/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;;/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);;1H2/q;+3;/p-3/t31-,34-,35-,36-,37+,41-,52-,53-,56-,57+,59-,60+,61+,62+;;/m1../s1
InChI KeyYOZNUFWCRFCGIH-WZHZPDAFSA-K
Chemical Taxonomy
Description belongs to the class of organic compounds known as cobalamin derivatives. These are organic compounds containing a corrin ring, a cobalt atom, an a nucleotide moiety. Cobalamin Derivatives are actually derived from vitamin B12.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassTetrapyrroles and derivatives
Sub ClassCorrinoids
Direct ParentCobalamin derivatives
Alternative Parents
Substituents
  • Cobalamin
  • Metallotetrapyrrole skeleton
  • 1-ribofuranosylbenzimidazole
  • Pentose phosphate
  • Glycosyl compound
  • N-glycosyl compound
  • Pentose monosaccharide
  • Monosaccharide phosphate
  • Benzimidazole
  • Phosphoethanolamine
  • Dialkyl phosphate
  • Fatty acyl
  • N-substituted imidazole
  • Organic phosphoric acid derivative
  • Benzenoid
  • Fatty amide
  • Alkyl phosphate
  • Phosphoric acid ester
  • Monosaccharide
  • Imidazole
  • Heteroaromatic compound
  • Pyrrolidine
  • Tetrahydrofuran
  • Azole
  • Pyrroline
  • Carboxamide group
  • Ketimine
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Primary carboxylic acid amide
  • Propargyl-type 1,3-dipolar organic compound
  • Carboxylic acid derivative
  • Oxacycle
  • Organic 1,3-dipolar compound
  • Azacycle
  • Organic metal salt
  • Organic transition metal salt
  • Carbonyl group
  • Organic cobalt salt
  • Imine
  • Organic salt
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Alcohol
  • Organic zwitterion
  • Organic nitrogen compound
  • Organic oxygen compound
  • Primary alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Biological location:

Source:

Process

Naturally occurring process:

Role

Biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
logP-14ChemAxon
pKa (Strongest Acidic)1.82ChemAxon
pKa (Strongest Basic)-0.55ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count10ChemAxon
Polar Surface Area437.23 ŲChemAxon
Rotatable Bond Count16ChemAxon
Refractivity340.03 m³·mol⁻¹ChemAxon
Polarizability135.56 ųChemAxon
Number of Rings12ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-1404000009-d95c227e0c2a01a825adView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-2902000005-61bd391f47e0b9c2ba4bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0002-3930000015-9f00c742a0c9e52997c4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000e-2509000000-5c630ca334aea70d2a2dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-1900000000-be3cf15d7ba2b2a92d24View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-1900000000-545dabccb8cd6ce30e09View in MoNA
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biospecimen LocationsNot Available
Tissue LocationNot Available
Pathways
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00200
Phenol Explorer Compound IDNot Available
FoodDB IDFDB003166
KNApSAcK IDNot Available
Chemspider ID28534326
KEGG Compound IDC08230
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkHydroxocobalamin
METLIN ID6607
PubChem Compound15589840
PDB IDNot Available
ChEBI ID27786
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Seetharam B, Yammani RR: Cobalamin transport proteins and their cell-surface receptors. Expert Rev Mol Med. 2003 Jun 13;5(18):1-18. [PubMed:14585166 ]
  2. Weinberg JB, Sauls DL, Misukonis MA, Shugars DC: Inhibition of productive human immunodeficiency virus-1 infection by cobalamins. Blood. 1995 Aug 15;86(4):1281-7. [PubMed:7632933 ]
  3. van Kapel J, Spijkers LJ, Lindemans J, Abels J: Improved distribution analysis of cobalamins and cobalamin analogues in human plasma in which the use of thiol-blocking agents is a prerequisite. Clin Chim Acta. 1983 Jul 15;131(3):211-24. [PubMed:6883715 ]
  4. el Kholty S, Gueant JL, Bressler L, Djalali M, Boissel P, Gerard P, Nicolas JP: Portal and biliary phases of enterohepatic circulation of corrinoids in humans. Gastroenterology. 1991 Nov;101(5):1399-408. [PubMed:1936810 ]
  5. Van den Berg MP, Merkus P, Romeijn SG, Verhoef JC, Merkus FW: Hydroxocobalamin uptake into the cerebrospinal fluid after nasal and intravenous delivery in rats and humans. J Drug Target. 2003 Jul;11(6):325-31. [PubMed:14668053 ]
  6. Fahmy NR: Consumption of vitamin B12 during sodium nitroprusside administration in humans. Anesthesiology. 1981 Apr;54(4):305-9. [PubMed:7212330 ]
  7. Begley JA, Colligan PD, Chu RC: Transcobalamin II mediated delivery of albumin-bound hydroxocobalamin to human liver cells. Proc Soc Exp Biol Med. 1993 Nov;204(2):206-10. [PubMed:8415778 ]
  8. Andersson HC, Shapira E: Biochemical and clinical response to hydroxocobalamin versus cyanocobalamin treatment in patients with methylmalonic acidemia and homocystinuria (cblC). J Pediatr. 1998 Jan;132(1):121-4. [PubMed:9470012 ]

Enzymes

General function:
Involved in cobalamin binding
Specific function:
Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate (By similarity).
Gene Name:
MTR
Uniprot ID:
Q99707
Molecular weight:
140525.91
References
  1. Kolhouse JF, Utley C, Stabler SP, Allen RH: Mechanism of conversion of human apo- to holomethionine synthase by various forms of cobalamin. J Biol Chem. 1991 Dec 5;266(34):23010-5. [PubMed:1744096 ]
  2. Ogier de Baulny H, Gerard M, Saudubray JM, Zittoun J: Remethylation defects: guidelines for clinical diagnosis and treatment. Eur J Pediatr. 1998 Apr;157 Suppl 2:S77-83. [PubMed:9587031 ]
  3. Tkachuck RD, Weinstein PP, Mueller JF: Metabolic fate of cyanocobalamin taken up by Spirometra mansonoides spargana. J Parasitol. 1977 Aug;63(4):694-700. [PubMed:18565 ]
  4. Quadros EV, Jacobsen DW: The dynamics of cobalamin utilization in L-1210 mouse leukemia cells: a model of cellular cobalamin metabolism. Biochim Biophys Acta. 1995 Jun 9;1244(2-3):395-403. [PubMed:7599160 ]
  5. Rosenblatt DS, Thomas IT, Watkins D, Cooper BA, Erbe RW: Vitamin B12 responsive homocystinuria and megaloblastic anemia: heterogeneity in methylcobalamin deficiency. Am J Med Genet. 1987 Feb;26(2):377-83. [PubMed:3812589 ]
General function:
Involved in isomerase activity
Specific function:
Involved in the degradation of several amino acids, odd-chain fatty acids and cholesterol via propionyl-CoA to the tricarboxylic acid cycle. MCM has different functions in other species.
Gene Name:
MUT
Uniprot ID:
P22033
Molecular weight:
83133.755
References
  1. Willard HF, Rosenberg LE: Inborn errors of cobalamin metabolism: effect of cobalamin supplementation in culture on methylmalonyl CoA mutase activity in normal and mutant human fibroblasts. Biochem Genet. 1979 Feb;17(1-2):57-75. [PubMed:36882 ]
  2. Dayem LC, Carney JR, Santi DV, Pfeifer BA, Khosla C, Kealey JT: Metabolic engineering of a methylmalonyl-CoA mutase-epimerase pathway for complex polyketide biosynthesis in Escherichia coli. Biochemistry. 2002 Apr 23;41(16):5193-201. [PubMed:11955068 ]
  3. Mayatepek E, Hoffmann GF, Baumgartner R, Schulze A, Jakobs C, Trefz FK, Bremer HJ: Atypical vitamin B12-unresponsive methylmalonic aciduria in sibship with severe progressive encephalomyelopathy: a new genetic disease? Eur J Pediatr. 1996 May;155(5):398-403. [PubMed:8741039 ]
  4. Tkachuck RD, Weinstein PP, Mueller JF: Metabolic fate of cyanocobalamin taken up by Spirometra mansonoides spargana. J Parasitol. 1977 Aug;63(4):694-700. [PubMed:18565 ]
  5. Quadros EV, Jacobsen DW: The dynamics of cobalamin utilization in L-1210 mouse leukemia cells: a model of cellular cobalamin metabolism. Biochim Biophys Acta. 1995 Jun 9;1244(2-3):395-403. [PubMed:7599160 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in oxidoreductase activity
Specific function:
Involved in the reductive regeneration of cob(I)alamin cofactor required for the maintenance of methionine synthase in a functional state.
Gene Name:
MTRR
Uniprot ID:
Q9UBK8
Molecular weight:
77672.995
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
General function:
Involved in ATP binding
Specific function:
Not Available
Gene Name:
MMAB
Uniprot ID:
Q96EY8
Molecular weight:
27387.975
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
General function:
Involved in nucleotide binding
Specific function:
Probable GTPase. May function as chaperone. May be involved in the transport of cobalamin (Cbl) into mitochondria for the final steps of adenosylcobalamin (AdoCbl) synthesis
Gene Name:
MMAA
Uniprot ID:
Q8IVH4
Molecular weight:
46537.9
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Manoli I, Sloan JL, Venditti CP: Isolated Methylmalonic Acidemia. 1993. [PubMed:20301409 ]
General function:
Involved in cobalamin binding
Specific function:
May be involved in the binding and intracellular trafficking of cobalamin (vitamin B12)
Gene Name:
MMACHC
Uniprot ID:
Q9Y4U1
Molecular weight:
31728.1
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Lerner-Ellis JP, Tirone JC, Pawelek PD, Dore C, Atkinson JL, Watkins D, Morel CF, Fujiwara TM, Moras E, Hosack AR, Dunbar GV, Antonicka H, Forgetta V, Dobson CM, Leclerc D, Gravel RA, Shoubridge EA, Coulton JW, Lepage P, Rommens JM, Morgan K, Rosenblatt DS: Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type. Nat Genet. 2006 Jan;38(1):93-100. Epub 2005 Nov 27. [PubMed:16311595 ]

Transporters

General function:
Involved in cobalamin binding
Specific function:
Vitamin B12-binding protein. Transports cobalamin into cells
Gene Name:
TCN1
Uniprot ID:
P20061
Molecular weight:
48206.3
References
  1. MacDonald CM, Farquharson J, Bessent RG, Adams JF: The forms of vitamin B12 on the transcobalamins. Clin Sci Mol Med. 1977 Feb;52(2):215-8. [PubMed:844253 ]
  2. Rothenberg SP, Marcoullis GP, Schwarz S, Lader E: Measurement of cyanocobalamin in serum by a specific radioimmunoassay. J Lab Clin Med. 1984 Jun;103(6):959-72. [PubMed:6726060 ]
General function:
Involved in calcium ion binding
Specific function:
Cotransporter which plays a role in lipoprotein, vitamin and iron metabolism, by facilitating their uptake. Binds to ALB, MB, Kappa and lambda-light chains, TF, hemoglobin, GC, SCGB1A1, APOA1, high density lipoprotein, and the GIF-cobalamin complex. The binding of all ligands required calcium. Serves as important transporter in several absorptive epithelia, including intestine, renal proximal tubules and embryonic yolk sac. Interaction with LRP2 mediates its trafficking throughout vesicles and facilitates the uptake of specific ligands like GC, hemoglobin, ALB, TF and SCGB1A1. Interaction with AMN controls its trafficking to the plasma membrane and facilitates endocytosis of ligands. May play an important role in the development of the peri-implantation embryo through internalization of APOA1 and cholesterol. Binds to LGALS3 at the maternal-fetal interface
Gene Name:
CUBN
Uniprot ID:
O60494
Molecular weight:
398672.8
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Seetharam B, Yammani RR: Cobalamin transport proteins and their cell-surface receptors. Expert Rev Mol Med. 2003 Jun 13;5(18):1-18. [PubMed:14585166 ]
General function:
Involved in multicellular organismal development
Specific function:
Necessary for efficient absorption of vitamin B12. May direct the production of trunk mesoderm during development by modulating a bone morphogenetic protein (BMP) signaling pathway in the underlying visceral endoderm
Gene Name:
AMN
Uniprot ID:
Q9BXJ7
Molecular weight:
47753.9
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Seetharam B, Yammani RR: Cobalamin transport proteins and their cell-surface receptors. Expert Rev Mol Med. 2003 Jun 13;5(18):1-18. [PubMed:14585166 ]