Human Metabolome Database Version 3.5

Showing metabocard for Cobalamin (HMDB02174)

Record Information
Version 3.5
Creation Date 2006-05-22 08:17:39 -0600
Update Date 2013-07-24 11:53:38 -0600
HMDB ID HMDB02174
Secondary Accession Numbers None
Metabolite Identification
Common Name Cobalamin
Description Cobalamin 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 Link_out, 17822656 Link_out).
Structure Thumb
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
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 Formula C62H88CoN13O14P
Average Molecular Weight 1329.3478
Monoisotopic Molecular Weight 1328.564331295
IUPAC Name cobalt(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 IUPAC Name cobalt(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 Number 13408-78-1
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 Key NSLAUEAQDBERRV-UHFFFAOYSA-L
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Lipids
Class Prenol Lipids
Sub Class Terpene Glycosides
Other Descriptors
  • Aromatic Heteropolycyclic Compounds
  • Benzimidazole Nucleosides and Nucleotides
  • a vitamin B<sub>12</sub>(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 Parent Diterpene Glycosides
Ontology
Status Detected 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
State Solid
Experimental Properties
Property Value Reference
Melting Point Not Available Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 0.0095 g/L ALOGPS
LogP 3.10 ALOGPS
LogP -2.5 ChemAxon
LogS -5.18 ALOGPS
pKa (strongest acidic) 1.84 ChemAxon
pKa (strongest basic) 8.98 ChemAxon
Hydrogen Acceptor Count 17 ChemAxon
Hydrogen Donor Count 9 ChemAxon
Polar Surface Area 460.05 A2 ChemAxon
Rotatable Bond Count 26 ChemAxon
Refractivity 330.72 ChemAxon
Polarizability 134.66 ChemAxon
Formal Charge 1 ChemAxon
Physiological Charge 2 ChemAxon
Spectra
Not Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue Location
  • Fibroblasts
  • Intestine
  • Placenta
  • Erythrocyte
  • Liver
  • Myelin
Pathways Not Available
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
0.0002 (0.00012 - 0.00026) uM Infant (0-1 year old) Not Specified Normal
Blood Detected and Quantified
0.0003 ( 0.0023 - 0.00046) uM Infant (0-1 year old) Not Specified Normal
Blood Detected and Quantified
0.0003 ( 0.00015 - 0.00055) uM Adult (>18 years old) Female Normal
Blood Detected and Quantified
0.0002 (0.0001 - 0.00033) uM Adult (>18 years old) Female Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
1.581e-05 +/- 3.462e-06 uM Not Specified Not Specified Normal
Cerebrospinal Fluid (CSF) Detected and Quantified
1e-05-4e-05 uM Newborn (0-30 days old) Not Specified Normal
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Cerebrospinal Fluid (CSF) Detected and Quantified 2.100e-05 +/- 7.301e-06 uM Adult (>18 years old) Both Relapse-Remitting Multiple Sclerosis
Cerebrospinal Fluid (CSF) Detected and Quantified 1.912e-05 +/- 6.0000e-06 uM Adult (>18 years old) Both Secondary-Progressive Multiple Sclerosis
Associated Disorders and Diseases
Disease References None
Associated OMIM IDs None
DrugBank ID Not Available
DrugBank Metabolite ID Not Available
Phenol Explorer Compound ID Not Available
Phenol Explorer Metabolite ID Not Available
FoodDB ID FDB022886
KNApSAcK ID Not Available
Chemspider ID 4942647 Link_out
KEGG Compound ID C05776 Link_out
BioCyc ID ADENOSYLCOBALAMIN-5-P Link_out
BiGG ID Not Available
Wikipedia Link Cobalamin Link_out
NuGOwiki Link HMDB02174 Link_out
Metagene Link HMDB02174 Link_out
METLIN ID 6527 Link_out
PubChem Compound 6438156 Link_out
PDB ID Not Available
ChEBI ID 28911 Link_out
References
Synthesis Reference Abou-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. 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 Link_out
  2. 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 Link_out
  3. 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 Link_out
  4. 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 Link_out
  5. 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 Link_out
  6. 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 Link_out
  7. 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 Link_out
  8. 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 Link_out
  9. 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 Link_out
  10. 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 Link_out
  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 Link_out
  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 Link_out
  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 Link_out

Enzymes
Name: Methionine synthase
Reactions: Not Available
Gene Name: MTR
Uniprot ID: Q99707 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Methylmalonyl-CoA mutase, mitochondrial
Reactions: Not Available
Gene Name: MUT
Uniprot ID: P22033 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Methylmalonic aciduria type A protein, mitochondrial
Reactions: Not Available
Gene Name: MMAA
Uniprot ID: Q8IVH4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Methylmalonic aciduria and homocystinuria type C protein
Reactions: Not Available
Gene Name: MMACHC
Uniprot ID: Q9Y4U1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: CD320 antigen
Reactions: Not Available
Gene Name: CD320
Uniprot ID: Q9NPF0 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Putative uncharacterized protein TCN2
Reactions: Not Available
Gene Name: TCN2
Uniprot ID: B5MBX2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Transporters
Name: Transcobalamin-2
Reactions: Not Available
Gene Name: TCN2
Uniprot ID: P20062 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Transcobalamin-1
Reactions: Not Available
Gene Name: TCN1
Uniprot ID: P20061 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Gastric intrinsic factor
Reactions: Not Available
Gene Name: GIF
Uniprot ID: P27352 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
Name: Cubilin
Reactions: Not Available
Gene Name: CUBN
Uniprot ID: O60494 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA