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Record Information
Version3.6
Creation Date2006-05-22 14:17:39 UTC
Update Date2013-07-24 17:53:38 UTC
HMDB IDHMDB02174
Secondary Accession NumbersNone
Metabolite Identification
Common NameCobalamin
DescriptionCobalamin participates in two enzymatic processes in mammalian cells. In the methionine synthase (EC 2.1.1.13) reaction, homocysteine (HCys) is converted to methionine allowing for the "recycling" of 5-methyl-tetrahydrofolate (THF) to N5,10 methylene-THF which is needed for the de novo synthesis of thymidylic acid and ultimately, for DNA formation. Since conversion of N5,10-methylene-THF to N5-methyl-THF is irreversible, cobalamin deficiency "traps" folic acid as N5-methyl-THF. Concurrently, HCys accumulates while methionine decreases, leading to a decrease in S-adenosylmethionine which further limits N5,10-methylene-THF formation by decreasing the synthesis of formyl-THF ("formate starvation"). Decreased methionine and S-adenosylmethionine may limit many methylation reactions including those involving DNA and myelin basic protein. In the methylmalonyl CoA mutase (EC 5.1.99.1) reaction, methylmalonyl CoA, derived from propionic acid synthesized by intestinal bacteria, is converted to succinyl CoA, a precursor for fatty acid and heme synthesis Thus, cobalamin deficiency results in methylmalonic acid (MMA) accumulation. Cobalamin deficiency causes megaloblastic anemia and neurocognitive abnormalities but effects on immune function and bone formation have also been described. Low serum cobalamin levels increase the risk of osteoporosis. Tests for cobalamin deficiency include measurements of 1) total cobalamin; 2) MMA and HCys, as indices of functional cobalamin deficiency; and 3) holotranscobalamin as a measure of the metabolically active fraction of circulating cobalamin. Each approach has significant limitations. Moreover, since the pathogenesis of neurologic dysfunction in cobalamin deficiency remains unclear, these tests may not be reliable markers of neurocognitive impairment. Subtle cobalamin deficiency, defined as elevated metabolite levels usually in asymptomatic patients with low or normal serum cobalamin values, is prevalent in the elderly and has been associated with food cobalamin malabsorption, a disorder characterized by the inability to release vitamin B12 from food or from its binding proteins. Malabsorption is often unrecognized or not investigated. However, because of the potential seriousness of the complications, particularly neuropsychiatric and hematological investigation of all patients who present with vitamin or nutritional deficiency is required. Classic disorders, such as pernicious anemia, are the cause of cobalamin deficiency in only a limited proportion of elderly patients. Epidemiological studies have shown a prevalence of cobalamin deficiency of around 20% in the elderly population of industrialized countries (between 50% and 60%, depending on the definition of cobalamin deficiency used in the study). New routes of cobalamin administration (oral and nasal) are currently being developed, especially the use of oral cobalamin therapy to treat food-cobalamin malabsorption. (PMID: 16814909 , 17822656 ).
Structure
Thumb
Synonyms
  1. 5,6-Dimethyl-1-a-D-ribofuranosyl-1H-benzimidazole
  2. 5,6-Dimethyl-1-a-D-ribofuranosylbenzimidazole
  3. 5,6-Dimethyl-1-alpha-delta-ribofuranosyl-1H-benzimidazole
  4. 5,6-Dimethyl-1-alpha-delta-ribofuranosylbenzimidazole
  5. Cob(III)alamin
  6. Cobalamin (III)
  7. Cobalamine
  8. Cobinamide ion(1+) dihydrogen phosphate (ester) inner salt 3'-ester
  9. Cobinamide ion(1+) dihydrogen phosphate (ester) inner salt 3'-ester with 5,6-dimethyl-1-alpha-delta-ribofuranosyl-1H-benzimidazole
  10. Hydroxomin
  11. Rubivite
  12. Rubratope-57
  13. Rubratope-60
  14. Ruvite
  15. Vitamin B12
Chemical FormulaC62H88CoN13O14P
Average Molecular Weight1329.3478
Monoisotopic Molecular Weight1328.564331295
IUPAC Namecobalt(3+) ion 4,9,14-tris(2-carbamoylethyl)-3,8,19-tris(carbamoylmethyl)-18-{2-[(2-{[5-(5,6-dimethyl-1H-1,3-benzodiazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl phosphonato]oxy}propyl)carbamoyl]ethyl}-2,3,6,8,13,13,16,18-octamethyl-20,21,22,23-tetraazapentacyclo[15.2.1.1^{2,5}.1^{7,10}.1^{12,15}]tricosa-5(23),6,10(22),11,15(21),16-hexaen-20-ide
Traditional Namecobalt(3+) 4,9,14-tris(2-carbamoylethyl)-3,8,19-tris(carbamoylmethyl)-18-{2-[(2-{[5-(5,6-dimethyl-1,3-benzodiazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl phosphonato]oxy}propyl)carbamoyl]ethyl}-2,3,6,8,13,13,16,18-octamethyl-20,21,22,23-tetraazapenta
CAS Registry Number13408-78-1
SMILES
[Co+3].CC(CNC(=O)CCC1(C)C(CC(N)=O)C2[N-]\C1=C(C)/C1=N/C(=C\C3=N\C(=C(C)/C4=NC2(C)C(C)(CC(N)=O)C4CCC(N)=O)\C(C)(CC(N)=O)C3CCC(N)=O)/C(C)(C)C1CCC(N)=O)OP([O-])(=O)OC1C(CO)OC(C1O)N1C=NC2=C1C=C(C)C(C)=C2
InChI Identifier
InChI=1S/C62H90N13O14P.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;/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);/q;+3/p-2
InChI KeyNSLAUEAQDBERRV-UHFFFAOYSA-L
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassLipids
ClassPrenol Lipids
Sub ClassTerpene Glycosides
Other Descriptors
  • Aromatic Heteropolycyclic Compounds
  • Benzimidazole Nucleosides and Nucleotides
  • a vitamin B12(Cyc)
  • an organometallic compound(Cyc)
Substituents
  • Benzimidazole
  • Carboxamide Group
  • Corrin
  • Diterpene
  • Enamine
  • Glycosyl Compound
  • Imidazole
  • Imine
  • Metallotetrapyrrole Skeleton
  • N Glycosyl Compound
  • Organic Hypophosphite
  • Organic Phosphite
  • Organic Transition Metal Moeity
  • Organometallic Compound
  • Oxolane
  • Pentose Monosaccharide
  • Phosphoethanolamine
  • Phosphoric Acid Ester
  • Primary Alcohol
  • Primary Carboxylic Acid Amide
  • Pyrrolidine
  • Pyrroline
  • Saccharide
  • Secondary Alcohol
  • Secondary Carboxylic Acid Amide
  • Tetrapyrrole Skeleton
  • Toluene
Direct ParentDiterpene Glycosides
Ontology
StatusDetected and Quantified
Origin
  • Drug
  • Food
Biofunction
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0095ALOGPS
logP3.1ALOGPS
logP-2.5ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)1.84ChemAxon
pKa (Strongest Basic)8.98ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count17ChemAxon
Hydrogen Donor Count9ChemAxon
Polar Surface Area460.05 Å2ChemAxon
Rotatable Bond Count26ChemAxon
Refractivity330.72 m3·mol-1ChemAxon
Polarizability134.66 Å3ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue Location
  • Erythrocyte
  • Fibroblasts
  • Intestine
  • Liver
  • Myelin
  • Placenta
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0002 (0.00012 - 0.00026) uMInfant (0-1 year old)Not SpecifiedNormal details
BloodDetected and Quantified0.0003 ( 0.0023 - 0.00046) uMInfant (0-1 year old)Not SpecifiedNormal details
BloodDetected and Quantified0.0003 ( 0.00015 - 0.00055) uMAdult (>18 years old)FemaleNormal details
BloodDetected and Quantified0.0002 (0.0001 - 0.00033) uMAdult (>18 years old)FemaleNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified1.581e-05 +/- 3.462e-06 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified1e-05-4e-05 uMNewborn (0-30 days old)Not SpecifiedNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
Cerebrospinal Fluid (CSF)Detected and Quantified2.100e-05 +/- 7.301e-06 uMAdult (>18 years old)BothRelapse-Remitting Multiple Sclerosis details
Cerebrospinal Fluid (CSF)Detected and Quantified1.912e-05 +/- 6.0000e-06 uMAdult (>18 years old)BothSecondary-Progressive Multiple Sclerosis details
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022886
KNApSAcK IDNot Available
Chemspider ID4942647
KEGG Compound IDC05776
BioCyc IDADENOSYLCOBALAMIN-5-P
BiGG IDNot Available
Wikipedia LinkCobalamin
NuGOwiki LinkHMDB02174
Metagene LinkHMDB02174
METLIN ID6527
PubChem Compound6438156
PDB IDNot Available
ChEBI ID28911
References
Synthesis ReferenceAbou-Zeid, A. A.; El-Sherbeeny, M. R. Production of cobalamin by Streptomyces olivaceus. Indian Journal of Technology (1976), 14(7), 357-9.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Fyfe JC, Madsen M, Hojrup P, Christensen EI, Tanner SM, de la Chapelle A, He Q, Moestrup SK: The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. Blood. 2004 Mar 1;103(5):1573-9. Epub 2003 Oct 23. Pubmed: 14576052
  2. Urban G, Pietrzik K, Hotzel D: [Radiological investigations of cobalamin supply with regard to folate status (author's transl)] Int J Vitam Nutr Res. 1981;51(2):124-31. Pubmed: 7287335
  3. Kanazawa S, Herbert V: Total corrinoid, cobalamin (vitamin B12), and cobalamin analogue levels may be normal in serum despite cobalamin in liver depletion in patients with alcoholism. Lab Invest. 1985 Jul;53(1):108-10. Pubmed: 4010227
  4. Minato H, Inada A, Kozaka S: [The effect of the external biliary diversion on cobalamin functions] Nippon Geka Gakkai Zasshi. 1995 Oct;96(10):695-702. Pubmed: 8538588
  5. Hansen PK, Byskov J, Gimsing P, Hippe E, Ladefoged K: Cobalamin absorption determined by the stool spot test. Reliability in patients with uremia or disorders of the ileum. Scand J Gastroenterol. 1986 Apr;21(3):341-7. Pubmed: 3086965
  6. Ermens AA, Vlasveld LT, van Marion-Kievit JA, Lensen CJ, Lindemans J: [The significance of an elevated cobalamin concentration in the blood] Ned Tijdschr Geneeskd. 2002 Mar 9;146(10):459-64. Pubmed: 11913109
  7. Lott WB, Takyar SS, Tuppen J, Crawford DH, Harrison M, Sloots TP, Gowans EJ: Vitamin B12 and hepatitis C: molecular biology and human pathology. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):4916-21. Epub 2001 Apr 10. Pubmed: 11296247
  8. Haltmayer M, Mueller T, Poelz W: Erythrocyte mean cellular volume and its relation to serum homocysteine, vitamin B12 and folate. Acta Med Austriaca. 2002;29(2):57-60. Pubmed: 12050947
  9. Baker H, Leevy CB, DeAngelis B, Frank O, Baker ER: Cobalamin (vitamin B12) and holotranscobalamin changes in plasma and liver tissue in alcoholics with liver disease. J Am Coll Nutr. 1998 Jun;17(3):235-8. Pubmed: 9627908
  10. Watkins D, Matiaszuk N, Rosenblatt DS: Complementation studies in the cblA class of inborn error of cobalamin metabolism: evidence for interallelic complementation and for a new complementation class (cblH). J Med Genet. 2000 Jul;37(7):510-3. Pubmed: 10882753
  11. Ermens AA, Vlasveld LT, Lindemans J: Significance of elevated cobalamin (vitamin B12) levels in blood. Clin Biochem. 2003 Nov;36(8):585-90. Pubmed: 14636871
  12. Solomon LR: Disorders of cobalamin (vitamin B12) metabolism: emerging concepts in pathophysiology, diagnosis and treatment. Blood Rev. 2007 May;21(3):113-30. Epub 2006 Jul 11. Pubmed: 16814909
  13. Andres E, Vidal-Alaball J, Federici L, Loukili NH, Zimmer J, Kaltenbach G: Clinical aspects of cobalamin deficiency in elderly patients. Epidemiology, causes, clinical manifestations, and treatment with special focus on oral cobalamin therapy. Eur J Intern Med. 2007 Oct;18(6):456-62. Epub 2007 Jul 12. Pubmed: 17822656

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
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
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
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
General function:
Involved in growth factor activity
Specific function:
Germinal center-B (GC-B) cells differentiate into memory B-cells and plasma cells (PC) through interaction with T-cells and follicular dendritic cells (FDC). CD320 augments the proliferation of PC precursors generated by IL-10. Receptor for the cellular uptake of transcobalamin bound cobalamin
Gene Name:
CD320
Uniprot ID:
Q9NPF0
Molecular weight:
28990.6
General function:
Involved in cobalamin binding
Specific function:
Not Available
Gene Name:
TCN2
Uniprot ID:
B5MBX2
Molecular weight:
47142.1

Transporters

General function:
Involved in cobalamin binding
Specific function:
Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells
Gene Name:
TCN2
Uniprot ID:
P20062
Molecular weight:
47534.5
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
General function:
Involved in cobalamin binding
Specific function:
Promotes absorption of the essential vitamin cobalamin (Cbl) in the ileum by specific receptor-mediated endocytosis
Gene Name:
GIF
Uniprot ID:
P27352
Molecular weight:
45415.7
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