Identification

Name
Cyanocobalamin
Accession Number
DB00115  (NUTR00004, APRD00326, EXPT00965)
Type
Small Molecule
Groups
Approved, Nutraceutical
Description

Cyanocobalamin (commonly known as Vitamin B12) is the most chemically complex of all vitamins.

Its chemical structure is based on a corrin ring, which, although quite similar to the porphyrin ring found in heme, chlorophyll, and cytochrome, has two of the pyrrole rings directly bonded. The central metal ion in cyanocobalamin is Co (cobalt). Cyanocobalamin (Vitamin B12) is not produced by plants or by animals. The only organisms that have the enzymes required for the synthesis of cyanocobalamin are bacteria and archaea [10].

Higher plants do not utilize cyanocobalamin from the soil, and are therefore a poor source of the substance as compared with animal tissues, which are potent in cyanocobalamin [10].

Vitamin B12 is naturally found in animal products, including fish, meat, poultry, eggs, milk, and milk products. Vitamin B12 is generally not present in plant foods, but fortified breakfast cereals are a readily available source of vitamin B12 with high bioavailability for vegetarian consumers. Various nutritional yeast products also contain vitamin B12 [12].

The main causes of vitamin B12 deficiency include vitamin B12 malabsorption, pernicious anemia, postsurgical malabsorption, and lastly, dietary deficiency. In many cases, however, the cause of deficiency is unknown [12].

Structure
Thumb
Synonyms
  • Cyanocob(III)alamin
  • Vitamin B12
  • Vitamin B12 complex
  • Vitamin B12 NOS
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
B-12 1000 Inj 1000mcg/mlSolution1 mgIntramuscular; SubcutaneousOmega Laboratories Ltd1985-12-31Not applicableCanada
Bedoz 1000injLiquid1 mgIntramuscularLab Nadeau LtÉe, Division Of Technilab Inc.1951-12-312005-08-05Canada
Cataplex B12 Tab 6mcgTablet6 mcgOralStandard Process Inc.Not applicableNot applicableCanada
Cobex Inj 1000mcg/mlSolution1 mgIntramuscular; SubcutaneousKripps Pharmacy Ltd.1979-12-31Not applicableCanada
Crystalline Vitamin B12-liq Im Sc 1000mcg/mlLiquid1 mgIntramuscular; SubcutaneousGermiphene Corporation1996-12-311999-06-28Canada
Cyanocobalamin Injection USPSolution1000 mcgIntramuscular; SubcutaneousTeligent OuNot applicableNot applicableCanada
Cyanocobalamin Injection USPLiquid1000 mcgIntramuscular; SubcutaneousTeligent Ou2018-01-16Not applicableCanada
Cyanocobalamin Injection USP 1000mcg/mlLiquid1 mgIntramuscular; SubcutaneousTaro Pharmaceuticals, Inc.1987-12-31Not applicableCanada
Cyanocobalamin Injection, USPLiquid1 mgIntramuscular; SubcutaneousSterimax Inc1992-12-31Not applicableCanada
Cyanocobalamin Injection, USPSolution1000 mcgIntramuscular; SubcutaneousMylan Pharmaceuticals2014-07-25Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Aj-cyanocobalaminSolution1000 mcgIntramuscular; SubcutaneousAgila Jamp Canada IncNot applicableNot applicableCanada
B12 Inject KitKitIntramuscular; SubcutaneousOaklock, Llc2015-07-08Not applicableUs
B12 Inject KitKitIntramuscular; SubcutaneousOaklock, Llc2015-06-19Not applicableUs
CyanocobalaminInjection1000 ug/mLIntramuscular; SubcutaneousWest Ward Pharmaceutical1971-10-20Not applicableUs
CyanocobalaminInjection1000 ug/mLIntramuscular; SubcutaneousSomerset Therapeutics, Llc2016-06-16Not applicableUs
CyanocobalaminInjection, solution1000 ug/mLIntramuscular; SubcutaneousPhysicians Total Care, Inc.2003-09-18Not applicableUs
CyanocobalaminInjection, solution1000 ug/mLIntramuscularAmerican Regent2003-05-29Not applicableUs
CyanocobalaminInjection, solution1000 ug/mLIntramuscularGeneral Injectables & Vaccines2010-07-01Not applicableUs
CyanocobalaminInjection, solution1000 ug/mLIntramuscularCardinal Health1990-09-302018-01-28Us
CyanocobalaminInjection, solution1000 ug/mLIntramuscular; SubcutaneousFresenius Kabi2000-10-18Not applicableUs
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
B-12 1000mcg Continuous Released TabTablet, extended release1 mgOralGahler Enterprises Ltd.1981-12-312000-10-03Canada
B-plexTablet50 mcgOralBeverly International Nutrition1986-12-311998-08-01Canada
B12 1000mcgTablet1000 mcgOralNatural Factors Nutritional Products Ltd.2000-09-012007-08-07Canada
B12 250mcg CyanocobalaminTablet250 mcgOralWn Pharmaceuticals Ltd.2001-10-012009-09-28Canada
Forphyll 3mcgTablet3 mcgOralTherapeutic Foods Co.1989-12-152004-07-22Canada
Gsf Tab 24mcgTablet24 mcgOralNutri Dyn Products Ltd.1980-12-311996-09-09Canada
Puro Sang Tab 1mcgTablet1 mcgOralPharmetics (2011) Inc.1966-12-312001-07-26Canada
Vit B12 Ctr Srt 1200mcgTablet, extended release1.2 mgOralBioenergy Inc.1979-12-311998-06-03Canada
Vit B12 Tab 500mcgTablet500 mcgOralPure Life International Prods Inc.1992-12-312001-08-07Canada
Vitamin B 12 Tab 25mcgTablet.025 mgOralSwiss Herbal Remedies Ltd.1971-12-312003-09-10Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
24 Multivitamins + MineralsCyanocobalamin (25 mcg) + Ascorbic acid (150 mg) + Beta carotene (10000 unit) + Biotin (25 mcg) + Calcium (130 mg) + Cholecalciferol (400 unit) + Choline bitartrate (25 mg) + Chromium (20 mcg) + Copper (1 mg) + Ferrous fumarate (15 mg) + Folic Acid (.8 mg) + Inositol (25 mg) + Magnesium cation (65 mg) + Manganese (2 mg) + Molybdenum (20 mcg) + Niacin (25 mg) + Calcium pantothenate (25 mg) + Potassium Iodide (.1 mg) + Potassium cation (15 mg) + Pyridoxine hydrochloride (25 mg) + Racemethionine (25 mg) + Riboflavin (25 mg) + Selenium (20 mcg) + Thiamine hydrochloride (25 mg) + Vanadium (20 mcg) + Vitamin A palmitate (5000 unit) + Vitamin E (50 unit) + Zinc (10 mg)TabletOralStanley Pharmaceuticals, A Division Of Vita Health Products Inc.1997-04-302002-07-31Canada
50 PlusCyanocobalamin (20 mcg) + Ascorbic acid (200 mg) + Biotin (20 mcg) + Choline bitartrate (20 mg) + Folic Acid (.2 mg) + Inositol (20 mg) + Niacin (20 mg) + Calcium pantothenate (20 mg) + Pyridoxine hydrochloride (20 mg) + Racemethionine (20 mg) + Riboflavin (20 mg) + Thiamine hydrochloride (20 mg) + Vitamin A palmitate (10000 unit) + Vitamin D (400 unit) + Vitamin E (20 unit)TabletOralQuest Vitamins A Div Of Purity Life Health Products1998-08-042001-07-06Canada
50 Plus Multiple Vitamins & MineralsCyanocobalamin (25 mcg) + Ascorbic acid (90 mg) + Biotin (45 mcg) + Calcium (200 mg) + Cholecalciferol (400 unit) + Chromium (10 mcg) + Copper (2 mg) + Folic Acid (0.4 mg) + Magnesium cation (100 mg) + Manganese (5 mg) + Molybdenum (25 mcg) + Nicotinamide (40 mg) + Pantothenic acid (10 mg) + Potassium Iodide (0.15 mg) + Pyridoxine hydrochloride (3 mg) + Riboflavin (3.2 mg) + Selenium (25 mcg) + Thiamine mononitrate (2.25 mg) + Vanadium (10 mcg) + Vitamin A palmitate (6000 unit) + Zinc (15 mg)TabletOralGfr Pharma Ltd.2002-10-202004-06-15Canada
Adult Infuvite Multiple VitaminsCyanocobalamin (5 ug/10mL) + Ascorbic acid (200 mg/10mL) + Biotin (60 ug/10mL) + Cholecalciferol (200 [iU]/10mL) + D-alpha-Tocopherol acetate (10 [iU]/10mL) + Dexpanthenol (15 mg/10mL) + Folic Acid (600 ug/10mL) + Nicotinamide (40 mg/10mL) + Phylloquinone (150 ug/10mL) + Pyridoxine hydrochloride (6 mg/10mL) + Riboflavin 5'-phosphate sodium (3.6 mg/10mL) + Thiamine hydrochloride (6 mg/10mL) + Vitamin A palmitate (3300 [iU]/10mL)Injection, solutionIntravenousSandoz2005-05-18Not applicableUs
Adult Infuvite Multiple VitaminsCyanocobalamin (5 ug/10mL) + Ascorbic acid (200 mg/10mL) + Biotin (60 ug/10mL) + Cholecalciferol (200 [iU]/10mL) + D-alpha-Tocopherol acetate (10 [iU]/10mL) + Dexpanthenol (15 mg/10mL) + Folic Acid (600 ug/10mL) + Nicotinamide (40 mg/10mL) + Phylloquinone (150 ug/10mL) + Pyridoxine hydrochloride (6 mg/10mL) + Riboflavin 5'-phosphate sodium (3.6 mg/10mL) + Thiamine hydrochloride (6 mg/10mL) + Vitamin A palmitate (3300 [iU]/10mL)Injection, solutionIntravenousSandoz2005-05-18Not applicableUs
Adult Infuvite Multiple VitaminsCyanocobalamin (5 ug/10mL) + Ascorbic acid (200 mg/10mL) + Biotin (60 ug/10mL) + Cholecalciferol (200 [iU]/10mL) + D-alpha-Tocopherol acetate (10 [iU]/10mL) + Dexpanthenol (15 mg/10mL) + Folic Acid (600 ug/10mL) + Nicotinamide (40 mg/10mL) + Phylloquinone (150 ug/10mL) + Pyridoxine hydrochloride (6 mg/10mL) + Riboflavin 5'-phosphate sodium (3.6 mg/10mL) + Thiamine hydrochloride (6 mg/10mL) + Vitamin A palmitate (3300 [iU]/10mL)Injection, solutionIntravenousSandoz2003-06-16Not applicableUs
Adult Infuvite Multiple VitaminsCyanocobalamin (5 ug/10mL) + Ascorbic acid (200 mg/10mL) + Biotin (60 ug/10mL) + Cholecalciferol (200 [iU]/10mL) + D-alpha-Tocopherol acetate (10 [iU]/10mL) + Dexpanthenol (15 mg/10mL) + Folic Acid (600 ug/10mL) + Nicotinamide (40 mg/10mL) + Phylloquinone (150 ug/10mL) + Pyridoxine hydrochloride (6 mg/10mL) + Riboflavin 5'-phosphate sodium (3.6 mg/10mL) + Thiamine hydrochloride (6 mg/10mL) + Vitamin A palmitate (3300 [iU]/10mL)Injection, solutionIntravenousSandoz2003-06-16Not applicableUs
Advanced B & T FormulaCyanocobalamin (6.67 mcg) + Ascorbic acid (33.3 mg) + Calcium (200 mg) + Chromium (33.33 mcg) + Copper (0.5 mg) + Folic Acid (0.133 mg) + Iron (1.67 mg) + Magnesium (83.3 mg) + Manganese (3.33 mg) + Nicotinamide (6.67 mg) + Calcium pantothenate (5 mg) + Phosphorus (100 mg) + Potassium (16.67 mg) + Pyridoxine hydrochloride (6.67 mg) + Riboflavin (2.67 mg) + Selenium (33.33 mcg) + Silicon (0.333 mg) + Sodium molybdate (16.67 mcg) + Thiamine (2.67 mg) + Vanadium (8.33 mg) + Vitamin D (66.67 unit) + Zinc (5 mg)CapsuleOralNutraceutical CorporationNot applicableNot applicableCanada
Allbee C 800 TabCyanocobalamin (17 mcg) + Ascorbic acid (800 mg) + D-alpha-Tocopherol acetate (45 unit) + Nicotinamide (100 mg) + Calcium pantothenate (33 mg) + Pyridoxine hydrochloride (30 mg) + Riboflavin (17 mg) + Thiamine mononitrate (15 mg)TabletOralWhitehall Robins Inc.1994-12-312003-08-01Canada
Alsimine W Vitamins A DCyanocobalamin (10 mcg) + Calcium (13 mg) + Dexpanthenol (5 mg) + Dexpanthenol (400 unit) + Ferrous gluconate (16 mg) + Nicotinamide (40 mg) + Pyridoxine hydrochloride (3 mg) + Riboflavin 5'-phosphate sodium (2 mg) + Thiamine hydrochloride (4.5 mg) + Vitamin A (10000 unit)Capsule; LiquidOralAlsi Cie Ltee1978-12-312003-05-21Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Active FECyanocobalamin (30 ug/1) + Ascorbic acid (160 mg/1) + Beta carotene (2100 [iU]/1) + Cholecalciferol (400 [iU]/1) + Cupric oxide (1 mg/1) + Folic Acid (1250 ug/1) + Iron (75 mg/1) + Magnesium oxide (30 mg/1) + Nicotinamide (20 mg/1) + Pyridoxine hydrochloride (20 mg/1) + Riboflavin (4 mg/1) + Thiamine hydrochloride (4 mg/1) + Vitamin E (40 [iU]/1) + Zinc oxide (20 mg/1)TabletOralGm Pharmaceuticals2013-11-11Not applicableUs
Animi-3Cyanocobalamin (500 ug/1) + Cholecalciferol (1000 [iU]/1) + Doconexent (250 mg/1) + Folic Acid (1 mg/1) + Icosapent (35 mg/1) + Omega-3 fatty acids (500 mg/1) + Pyridoxine hydrochloride (12.5 mg/1) + Soy sterol (200 mg/1)CapsuleOralPbm Pharmaceuticals Inc.2011-06-01Not applicableUs
Animi-3 with Vitamin DCyanocobalamin (500 ug/1) + Cholecalciferol (1000 [iU]/1) + Doconexent (250 mg/1) + Folic Acid (1 mg/1) + Icosapent (35 mg/1) + Omega-3 fatty acids (500 mg/1) + Pyridoxine hydrochloride (12.5 mg/1) + Soy sterol (200 mg/1)CapsuleOralPbm Pharmaceuticals Inc.2011-06-01Not applicableUs
Av-VITE FBCyanocobalamin (1 mg/1) + Folic Acid (2.5 mg/1) + Pyridoxine hydrochloride (25 mg/1)TabletOralAv Kare, Inc.2015-11-052016-01-20Us
BacminCyanocobalamin (50 ug/1) + Ascorbic acid (500 mg/1) + Biotin (150 ug/1) + Chromium Cr-51 chloride (.1 mg/1) + Cupric oxide (3 mg/1) + D-alpha-Tocopherol acetate (30 [iU]/1) + Ferrous fumarate (27 mg/1) + Flavone (50 mg/1) + Folic Acid (1 mg/1) + Magnesium oxide (50 mg/1) + Manganese gluconate (5 mg/1) + Nicotinamide (100 mg/1) + Calcium pantothenate (25 mg/1) + Pyridoxine hydrochloride (25 mg/1) + Riboflavin (20 mg/1) + Selenomethionine (50 ug/1) + Thiamine mononitrate (20 mg/1) + Vitamin A acetate (2000 [iU]/1) + Zinc oxide (22.5 mg/1)Tablet, coatedOralMarnel Pharmaceuticals, Llc2000-04-01Not applicableUs
BiferaRxCyanocobalamin (25 ug/1) + Folic Acid (1 mg/1) + Heme iron polypeptide (6 mg/1) + Iron Dextran (22 mg/1)TabletOralAlaven Pharmaceutical2010-05-01Not applicableUs68220 0085 90 nlmimage10 2d1316d8
BiferaRxCyanocobalamin (25 ug/1) + Folic Acid (1 mg/1) + Heme iron polypeptide (6 mg/1) + Iron Dextran (22 mg/1)TabletOralMeda Pharmaceuticals Ltd2012-10-31Not applicableUs
BioFerr 90Cyanocobalamin (16.8 ug/1) + Ascorbic acid (138 mg/1) + Docusate sodium (55 mg/1) + Ferrous gluconate (13.2 mg/1) + Folic Acid (1.4 mg/1) + Iron (88.5 mg/1)Tablet, film coatedOralBiocomp Pharma, Inc.2014-07-01Not applicableUs
C-Nate DHACyanocobalamin (15 ug/1) + Ascorbic acid (100 mg/1) + Cholecalciferol (400 [iU]/1) + Cupric sulfate (1 mg/1) + Ferrous fumarate (28 mg/1) + Folic Acid (1 mg/1) + Magnesium cation (30 mg/1) + Omega-3 fatty acids (200 mg/1) + Pyridoxine hydrochloride (20 mg/1) + Riboflavin (3 mg/1) + Thiamine mononitrate (3 mg/1) + Vitamin E (30 [iU]/1) + Zinc oxide (20 mg/1)Capsule, gelatin coatedOralCenturion Labs2013-01-01Not applicableUs
Calcium Folic Acid Plus D ChewableCyanocobalamin (125 ug/1) + Boron (250 ug/1) + Calcium Carbonate (1342 mg/1) + Cholecalciferol (300 [iU]/1) + Folic Acid (1 mg/1) + Magnesium cation (50 mg/1) + Pyridoxine (10 mg/1)WaferOralAcella Pharmaceuticals, LLC2010-03-23Not applicableUs
International/Other Brands
Bedodeka (Teva) / Bedoz / Berubigen (Upjohn) / Betalin (Lilly) / Cobione (MSD) / Cobolin-M / Crystamine / Cyanoject / Cyomin / Cytakon (GlaxoSmithKline) / Cytamen (GlaxoSmithKline) / Dicopac / Neuroforte-R / Primabalt / Rubramin PC / Vitabee 12
Categories
UNII
P6YC3EG204
CAS number
68-19-9
Weight
Average: 1355.3652
Monoisotopic: 1354.5674053
Chemical Formula
C63H88CoN14O14P
InChI Key
RMRCNWBMXRMIRW-WZHZPDAFSA-L
InChI
InChI=1S/C62H90N13O14P.CN.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;1-2;/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;;+2/p-2/t31-,34-,35-,36-,37+,41-,52-,53-,56-,57+,59-,60+,61+,62+;;/m1../s1
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-cyano-46-hydroxy-12-(hydroxymethyl)-5,6,17,23,28,31,31,36,38,41,42-undecamethyl-15,20-dioxo-11,14,16-trioxa-2λ⁵,9,19,26,43λ⁵,44λ⁵,45λ⁵-heptaaza-15λ⁵-phospha-1-cobaltadodecacyclo[27.14.1.1¹,³⁴.1²,⁹.1¹⁰,¹³.0¹,²⁶.0³,⁸.0²³,²⁷.0²⁵,⁴².0³²,⁴⁴.0³⁹,⁴³.0³⁷,⁴⁵]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
SMILES
[C@H]1([C@@H]2[C@H]([C@@H](N3C4=CC(=C(C)C=C4[N+]([Co-3]456(N7C8=C(C9=[N+]4C(C([C@@H]9CCC(N)=O)(C)C)=CC4=[N+]5C(=C(C5=[N+]6[C@@]([C@]7([C@@H]([C@@]8(C)CCC(=O)NC[C@@]([H])(C)OP([O-])(=O)O2)CC(N)=O)[H])([C@@]([C@@H]5CCC(N)=O)(C)CC(N)=O)C)C)[C@@]([C@@H]4CCC(N)=O)(C)CC(N)=O)C)C#N)=C3)C)O1)O)CO

Pharmacology

Indication

For treatment of pernicious anemia (due to lack of or inhibition of intrinsic factor) and for prevention and treatment of vitamin B 12 deficiency [12], [15].

Values below approximately 170–250 pg/mL (120–180 picomol/L) for adults suggest a vitamin B12 deficiency. Despite this, evidence suggests that serum vitamin B12 concentrations may not accurately reflect intracellular concentrations of the vitamin [12]. It is therefore difficult to diagnose vitamin B12 deficiency.

Associated Conditions
Pharmacodynamics

Vitamin B12, or methylcobalamin, is imperative for growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis. Cells which undergo rapid division (epithelial cells, bone marrow, myeloid cells) have the greatest requirement for methylcobalamin [15]. Cyanocobalamin (Vitamin B12) is a water-soluble organometallic compound with a trivalent cobalt ion bound inside a corrin ring. It is required for nerve cells and red blood cells, and to form DNA. Vitamin B12 deficiency is the cause of various forms of anemia [15].

Vitamin B12 deficiency results in megaloblastic anemia, gastrointestinal lesions, and neurologic damage (due to lack of myelin). Vitamin B12 requires an intrinsic factor-mediated active transport for absorption. Lack of or the inhibition of intrinsic factor may result in pernicious anemia [15].

Pernicious anemia is an autoimmune disease which damages the gastric mucosa, resulting in gastric atrophy. This leads to damage of the stomach parietal cells, achlorhydria (lack of gastric acid secretion), and failure to produce intrinsic factor, resulting in vitamin B12 malabsorption [15].

If pernicious anemia is not treated, it leads to vitamin B12 deficiency, eventually leading to megaloblastic anemia and neurological disorders, despite adequate dietary intake of vitamin B12 [12].

Mechanism of action

Vitamin B12 is used in the body in two forms: Methylcobalamin and 5-deoxyadenosyl cobalamin. The enzyme methionine synthase needs methylcobalamin as a cofactor. This enzyme is involved in the conversion of the amino acid homocysteine into methionine. Methionine, is required for DNA methylation [12], [15].

Vitamin B12 is converted to coenzyme B12 in tissues. This form is required for the conversion of methylmalonate to succinate and the synthesis of methionine from homocysteine (a reaction also requiring folate) [15]. Without coenzyme B12, tetrahydrofolate cannot be regenerated from its inactive storage form, 5-methyl tetrahydrofolate, leading to functional folate deficiency. Vitamin B12 also may be involved in maintaining sulfhydryl (SH) groups in the reduced form needed by many SH-activated enzyme systems [15].

Via the above reactions, vitamin B12 is associated with both fat and carbohydrate metabolism, as well as protein synthesis [15].

5-Deoxyadenosyl cobalamin is a cofactor needed by the enzyme that acts to convert L-methylmalonyl-CoA to succinyl-CoA. This conversion is an important step in the extraction of energy from proteins and fats. Additionally, succinyl CoA is necessary for the production of hemoglobin, the substance that carries oxygen in red blood cells [12].

L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to succinyl-CoA in the degradation of propionate, an important biochemical reaction in the metabolism of lipids and proteins. Succinyl-CoA is also required for hemoglobin synthesis [12].

TargetActionsOrganism
AMethionine synthase
cofactor
Human
AMethylmalonyl-CoA mutase, mitochondrial
cofactor
Human
UMethionine synthase reductase
cofactor
Human
UMethylmalonic aciduria type A protein, mitochondrial
cofactor
Human
UMethylmalonic aciduria and homocystinuria type C protein
cofactor
Human
UMethylenetetrahydrofolate reductase
cofactor
Human
Absorption

Approximately 56% of a 1 mcg oral dose of vitamin B12 is absorbed, however, absorption decreases significantly when intrinsic factor capacity is exceeded (at 1–2 mcg of vitamin B12) [12].

Readily absorbed in the lower half of the ileum [14].

Bioavailability of the nasal gel vitamin B12 and spray forms compared to intramuscular injection are about 9% and 6%, respectively [15].

Because the intranasal forms have lower absorption than the IM dosage form, intranasal B12 forms dosed administered once weekly. After 1 month of treatment in pernicious anemia, the weekly dosing of 500 mcg B12 intranasal gel resulted in a significant increase in B12 levels in comparison to a once-monthly 100 mcg IM dose [15].

Volume of distribution

Once absorbed, vitamin B12 is highly bound to transcobalamin II, a specific B-globulin carrier protein and is distributed and stored primarily in the liver as coenzyme B12 [15]. It has been found that the distribution of vitamin B12 is dependent on the current cobalamine status, from animal studies [14]. The bone marrow also stores a high amount of absorbed vitamin B12 [15].

This vitamin crosses the placenta and is found distributed in breast milk. Enterohepatic recirculation conserves systemic stores of Vitamin B12 [14].

Protein binding

Very high (to specific plasma proteins called transcobalamins); binding of hydroxocobalamin is slightly higher than cyanocobalamin [14].

Metabolism

Mainly Hepatic [9], [10].

Vitamin B12 serves as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase enyme. Methionine synthase catalyzes the conversion of homocysteine to methionine during metabolism. Methionine is necessary for the formation of S-adenosylmethionine, a universal methyl donor for about 100 substrates, including DNA, RNA, hormones, proteins, and lipids [12].

Vitamin B12, which is bound to protein in food, is released following the activity of hydrochloric acid and gastric protease in the stomach. When synthetic vitamin B12 is added to fortified foods and dietary supplements, it is found in the free form and, and does not require this separation step. Free vitamin B12 then binds with intrinsic factor (IF), a glycoprotein secreted by the parietal cells of the stomach, and the newly formed complex undergoes absorption within the distal ileum by receptor-mediated endocytosis [18].

Intestinal microorganisms produce cobalamin in the colon, however, not absorbed and thus vitamin B12 must be supplied with the food. In mammals, the assimilation and transport of dietary cobalamin is performed by three successive proteins, haptocorrin (HC), gastric intrinsic factor (IF) and transcoba- lamin. Cobalamin is required by cells for two enzyme cofactors, methyl-Cbl for methionine synthase and 50 -deoxyadenosyl-Cbl (Ado-Cbl) for methyl- malonyl-CoA mutase [15].

In the stomach, Cobalamin is firstly bound to salivary HC. Following proteolytic cleavage of HC into 2-3 fragments in the duodenum, and is then transferred to IF. Mucosal cells in the terminal ileum absorb the IF-Cobalamin complex by a process called endocytosis by the cubilin-amnionless receptor [15].

In the enterocyte (intestinal cell), Cobalamin is freed from IF and appears in the blood combined with transcobalamin which carries cobalamin to cells. Only the fraction of Cbl bound to TC is quickly taken up by endocytosis by a specific receptor of yet unknown structure, present on most cell types [15].

The other Cbl- transporting protein in plasma is homocysteine. Its ability to promote cellular uptake of cobalamin is found to be limited, but it is thought to serve as a storage protein as well as scavenger of inactive Cbl- analogues [18].

Route of elimination

In healthy individuals receiving only dietary vitamin B12, approximately 3 - 8 micrograms (mcg) of the vitamin is secreted into the GI tract daily, primarily from bile. Most excreted, however, 1 mcg is reabsorbed; less than 0.25 mcg is usually excreted in the urine daily. When vitamin B12 is administered in amounts that exceed the binding capacity of plasma, the liver, and other tissues, it’s free in the blood for urinary excretion [19].

Half life

Approximately 6 days (400 days in the liver) [10]

Clearance
Not Available
Toxicity

Anaphylactic reactions (skin rash, itching, wheezing) post parenteral administration has occurred.

The Institute of Medicine (IOM), USA, did not establish an upper limit for vitamin B12 because of its low potential for toxicity. In Dietary Reference Intakes [13]: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, the IOM declares that “no adverse effects have an association with excess vitamin B12 intake from both food and dietary supplements in healthy individuals” [13].

Findings from intervention trials support these conclusions. In the NORVIT and HOPE 2 trials, vitamin B12 supplementation (in combination with folic acid and vitamin B6) did not cause any serious adverse events when administered at doses of 0.4 mg for 40 months (NORVIT trial) and 1.0 mg for 5 years (HOPE 2 trial) [6, 7].

Parenteral methylcobalamin is classified as pregnancy category C. Adequate studies in humans have not been conducted; however, no maternal or fetal complications have been associated with doses that are recommended during pregnancy, and appropriate treatment should not be withheld from pregnant women with vitamin B12 responsive anemias. Conversely, pernicious anemia resulting from vitamin B12 deficiency may cause infertility or poor pregnancy outcomes. Vitamin B12 deficiency has occurred in breast-fed infants of vegetarian mothers whose diets contain no animal products (e.g., eggs, dairy), even though the mothers had no symptoms of deficiency at the time. Maternal requirements for vitamin B12 increase during pregnancy [12].

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
adenosylcobalamin salvage from cobinamideMetabolic
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
ChloramphenicolThe therapeutic efficacy of Cyanocobalamin can be decreased when used in combination with Chloramphenicol.Approved, Vet Approved
ColchicineThe serum concentration of Cyanocobalamin can be decreased when it is combined with Colchicine.Approved
Food Interactions
Not Available

References

Synthesis Reference

Robert H. Allen, "Preparation of samples for vitamin B12 and/or folate assay and assay." U.S. Patent US4451571, issued October, 1982.

US4451571
General References
  1. Wickramasinghe SN: Morphology, biology and biochemistry of cobalamin- and folate-deficient bone marrow cells. Baillieres Clin Haematol. 1995 Sep;8(3):441-59. [PubMed:8534956]
  2. Sharabi A, Cohen E, Sulkes J, Garty M: Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route. Br J Clin Pharmacol. 2003 Dec;56(6):635-8. [PubMed:14616423]
  3. Hall AH, Rumack BH: Hydroxycobalamin/sodium thiosulfate as a cyanide antidote. J Emerg Med. 1987;5(2):115-21. [PubMed:3295013]
  4. Andres E, Noel E, Goichot B: Metformin-associated vitamin B12 deficiency. Arch Intern Med. 2002 Oct 28;162(19):2251-2. [PubMed:12390080]
  5. Gilligan MA: Metformin and vitamin B12 deficiency. Arch Intern Med. 2002 Feb 25;162(4):484-5. [PubMed:11863489]
  6. Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, Rasmussen K: Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006 Apr 13;354(15):1578-88. doi: 10.1056/NEJMoa055227. Epub 2006 Mar 12. [PubMed:16531614]
  7. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr: Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006 Apr 13;354(15):1567-77. doi: 10.1056/NEJMoa060900. Epub 2006 Mar 12. [PubMed:16531613]
  8. Russell-Jones GJ, Alpers DH: Vitamin B12 transporters. Pharm Biotechnol. 1999;12:493-520. [PubMed:10742986]
  9. Seetharam B: Receptor-mediated endocytosis of cobalamin (vitamin B12). Annu Rev Nutr. 1999;19:173-95. doi: 10.1146/annurev.nutr.19.1.173. [PubMed:10448521]
  10. Cyanocobalamin [Link]
  11. Vitamin B12 [Link]
  12. Vitamin B 12 Health Professional Fact Sheet [Link]
  13. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline [Link]
  14. Tissue distribution of oral vitamin B12 is influenced by B12 status and B12 form: an experimental study in rats [Link]
  15. Methylcobalamin Injection [Link]
  16. Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency [Link]
  17. Vitamin B12 Transporters [Link]
  18. Vitamin B12 transport proteins: crystallographic analysis of beta-axial ligand substitutions in cobalamin bound to transcobalamin [Link]
  19. cyanocobalamin (vitamin B12) [Link]
  20. human ref: Vitamin B12 (cyanocobalamin) metabolism [Link]
  21. Methylcobalamin vs cyanocobalamin [Link]
  22. Teratogenic mechanisms for medical drugs [Link]
External Links
KEGG Drug
D00166
KEGG Compound
C02823
PubChem Compound
70678590
PubChem Substance
46509031
ChemSpider
21864832
ChEBI
17439
ChEMBL
CHEMBL2110563
PharmGKB
PA451892
HET
CNC
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Cyanocobalamin
ATC Codes
B03AE01 — Iron, vitamin b12 and folic acidB03BA51 — Cyanocobalamin, combinationsB03BA01 — Cyanocobalamin
AHFS Codes
  • 88:08.00 — Vitamin B Complex
FDA label
Download (202 KB)
MSDS
Download (37.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentBMI >30 kg/m2 / High Blood Pressure (Hypertension)1
0RecruitingTreatmentVitamin B 12 Deficiency1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Infection, Human Immunodeficiency Virus I / Mycobacterium avium complex infection1
1CompletedDiagnosticHealthy Volunteers1
1CompletedOtherHeart Rate / Heart Rate Variability / Inflammatory Reaction1
1CompletedPreventionHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
1CompletedTreatmentCancers / Metastases1
1CompletedTreatmentFocus: Bioavailability1
1Not Yet RecruitingBasic ScienceAging / Mineral deficiency / Vitamin Deficiency1
1RecruitingTreatmentLeptomeningeal Metastases1
1, 2CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm1
1, 2RecruitingTreatmentPostpartum Anemia1
1, 2SuspendedTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
1, 2TerminatedTreatmentPsoriasis1
2Active Not RecruitingTreatmentLung Cancers / Neoplasms Metastasis1
2CompletedPreventionDepression / Depressive Disorders1
2CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2RecruitingPreventionPeripheral T-cell lymphoma unspecified refractory / Relapsed Peripheral T-Cell Lymphoma1
2RecruitingPreventionVincristine Induced Peripheral Neuropathy (VIPN)1
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kidney Diseases1
2Unknown StatusTreatmentAnemias1
2Unknown StatusTreatmentMalignant Neoplasm of Nasopharynx1
2, 3CompletedTreatmentAtherosclerosis1
2, 3CompletedTreatmentAutistic Disorder1
2, 3CompletedTreatmentCardiovascular Disease (CVD) / Chronic Kidney Disease (CKD) / Mortality1
3CompletedPreventionCerebral Infarctions / Myocardial Infarction / Strokes1
3CompletedPreventionCerebrovascular Stroke / Coronary Artery Disease / Myocardial Infarction1
3CompletedPreventionComplications, Pregnancy / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentAlzheimer's Disease (AD)1
3CompletedTreatmentAnemia in End-Stage Renal Disease1
3CompletedTreatmentAnemias1
3CompletedTreatmentChronic Plaque Psoriasis1
3CompletedTreatmentDiarrheal Illnesses / Growth Faltering / Respiratory Illness1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis, Pulmonary1
3RecruitingTreatmentBladder Cancers / Transitional Cell Carcinoma / Ureteral Cancer1
3Unknown StatusNot AvailableAnemias / Low Birth Weight / Neonatal Mortality1
3Unknown StatusTreatmentAlzheimer's Disease (AD) / Down Syndrome (DS)1
4CompletedTreatmentDiabetic Peripheral Neuropathic Pain1
4CompletedTreatmentHyperemesis Gravidarum / Morning Sickness / Nausea / Pregnancy / Vomiting1
4CompletedTreatmentPregnancy1
4CompletedTreatmentVitamin B 12 Deficiency1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4TerminatedTreatmentAnemias1
4Unknown StatusDiagnosticVitamin B12 Deficiency1
4WithdrawnTreatmentNephritis / Proteinuria / Systemic Lupus Erythematosus (SLE)1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedNot AvailableVitamin B12 Deficiency1
Not AvailableCompletedDiagnosticCoronary Artery Disease / Major Surgery1
Not AvailableCompletedDiagnosticVitamin B12 Absorption1
Not AvailableCompletedPreventionDeep Vein Thrombosis (DVT) / Pulmonary Embolism (PE)1
Not AvailableCompletedPreventionNeural Tube Defects (NTDs)1
Not AvailableCompletedScreeningOther Diseases or Conditions1
Not AvailableCompletedSupportive CareNon-thyroidal Illness Syndrome1
Not AvailableCompletedTreatmentAcute Myocardial Infarction (AMI)1
Not AvailableCompletedTreatmentAngelman's syndrome / Nervous System Diseases1
Not AvailableCompletedTreatmentAutistic Disorder1
Not AvailableCompletedTreatmentEnd Stage Renal Disease (ESRD) / Hyperhomocysteinaemia1
Not AvailableCompletedTreatmentHealthy Volunteers1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentSleep Disorders, Circadian Rhythm1
Not AvailableCompletedTreatmentVitamin B 12 Deficiency1
Not AvailableNot Yet RecruitingPreventionPost Operative Cognitive Dysfunction1
Not AvailableTerminatedTreatmentRecurrent Aphthous Stomatitis1
Not AvailableWithdrawnPreventionStrokes / Transient Ischaemic Attack (TIA)1

Pharmacoeconomics

Manufacturers
  • Par pharmaceutical inc
  • Pharmacia and upjohn co
  • Eli lilly and co
  • Watson laboratories inc
  • Abraxis pharmaceutical products
  • Akorn inc
  • App pharmaceuticals llc
  • Baxter healthcare corp anesthesia and critical care
  • Bioniche pharma usa llc
  • Dell laboratories inc
  • Luitpold pharmaceuticals inc
  • Sanofi aventis us llc
  • Solopak medical products inc
  • Warner chilcott inc
  • Wyeth ayerst laboratories
  • Merck and co inc
  • Bel mar laboratories inc
  • Bristol myers squibb co
  • Savage laboratories inc div altana inc
  • Bayer healthcare pharmaceuticals inc
  • West ward pharmaceutical corp
  • Bracco diagnostics inc
Packagers
  • American Regent
  • APP Pharmaceuticals
  • Baxter International Inc.
  • Bayer Healthcare
  • C.O. Truxton Inc.
  • Cardinal Health
  • Carlisle Laboratories Inc.
  • Central Pharmaceuticals
  • Chain Drug
  • Choice Rx Ltd.
  • Clint Pharmaceutical Inc.
  • CVS Pharmacy
  • Darby Dental Supply Co. Inc.
  • General Injectables and Vaccines Inc.
  • Gonberetica
  • Gyn Nutriment Pharmacology
  • H and H Laboratories
  • International Ethical Labs Inc.
  • Ivax Pharmaceuticals
  • Keene Pharmaceuticals Inc.
  • Luitpold Pharmaceuticals Inc.
  • Major Pharmaceuticals
  • Martica Enterprises Inc.
  • Martin Surgical Supply
  • Mason Distributors
  • Mckesson Corp.
  • MDRNA Inc.
  • Merck & Co.
  • Merit Pharmaceuticals
  • National Pharmaceuticals
  • National Vitamin Company
  • Neuman Distributors Inc.
  • Par Pharmaceuticals
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Primedics Laboratories
  • Rite Aid Corp.
  • Rugby Laboratories
  • Spectrum Pharmaceuticals
  • Sunmark
  • Torrance Co.
  • Vitaline Corp.
  • Walgreen Co.
Dosage forms
FormRouteStrength
Capsule; liquidOral
TabletOral
ElixirOral
TabletOral1000 mcg
KitIntramuscular; Subcutaneous
LiquidIntramuscular1 mg
WaferOral
TabletOral6 mcg
SolutionIntramuscular; Subcutaneous1 mg
Capsule, liquid filledOral
InjectionIntramuscular; Subcutaneous1000 ug/mL
Injection, solutionIntramuscular1000 ug/mL
Injection, solutionIntramuscular; Subcutaneous1000 ug/mL
CapsuleOral
Tablet, effervescentOral
SyrupOral
Tablet, film coatedOral
LiquidIntramuscular; Intravenous
TabletOral24 mcg
Tablet, extended releaseOral
Injection, solutionIntravenous
PowderOral
Solution / dropsOral
LiquidIntravenous
Liquid; tabletOral
Injection, solution, concentrateIntravenous
SolutionIntravenous
SolutionOral
LiquidOral
Tablet, chewableOral
SprayNasal500 ug/1
Kit
Tablet, coatedOral
TabletOral1 mcg
LiquidIntramuscular; Intravenous; Subcutaneous1 mg
LiquidIntramuscular; Subcutaneous1000 mcg
LozengeOral
Capsule, extended releaseOral
Capsule, gelatin coatedOral
Tablet, extended releaseOral1.2 mg
TabletOral500 mcg
TabletOral.025 mg
CapsuleOral1000 mcg
LiquidIntramuscular; Subcutaneous1 mg
LiquidIntramuscular; Subcutaneous100 mcg
SolutionIntramuscular; Subcutaneous1000 mcg
TabletOral50 mcg
TabletOral1 mg
CapsuleOral500 mcg
SolutionIntramuscular; Subcutaneous100 mcg
Tablet, extended releaseOral1 mg
TabletOral250 mcg
TabletOral5 mcg
Kit
TabletOral100 mcg
TabletOral25 mcg
TabletOral3 mcg
Prices
Unit descriptionCostUnit
Nascobal 500 mcg/0.1ml Solution 2.3ml Bottle277.97USD bottle
Cyanocobalamin crystals161.18USD g
Infuvite pediatric vial2.58USD ml
Cyanocobalamin 1000 mcg/ml vial1.44USD vial
Cyanocobalamin 1000 mcg/ml1.2USD ml
Cyanocobalamin 1000 mcg/ml Solution1.03USD ml
Rubesol-1000 mcg/ml vial0.48USD ml
Vitamin B-12 1000 mcg/ml0.47USD ml
Vitamin b-12 2.5 mg tablet sl0.17USD tablet
Cyanocobalamin 1000 mcg tablet0.16USD tablet
Cyanocobalamin 100 mcg tablet0.14USD tablet
Vitamin b-12 1000 mcg tablet sl0.08USD tablet
B12 2500 mcg tablet sl0.07USD tablet
Sm vitamin b-12 500 mcg tablet0.06USD tablet
Vitamin b-12 1000 mcg tablet0.06USD tablet
Vitabee with vit c caplet0.05USD caplet
Vitamin b-12 500 mcg tablet0.05USD tablet
CVS Pharmacy vitamin b-12 1000 mcg tablet0.04USD tablet
CVS Pharmacy vitamin b-12 500 mcg tablet0.04USD tablet
Vitamin b-12 50 mcg tablet0.04USD tablet
CVS Pharmacy vitamin b12 100 mcg tablet0.03USD tablet
Pv vit b-12 1000 mcg tablet sl0.03USD tablet
Ra vitamin b-12 50 mcg tablet0.03USD tablet
Vitamin b-12 250 mcg tablet0.03USD tablet
Pv b-12 250 mcg tablet0.02USD tablet
Vitamin b-12 100 mcg tablet0.02USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7229636No2004-08-012024-08-01Us
US7879349No2004-08-012024-08-01Us
US8003353No2004-08-012024-08-01Us
US8940714No2004-02-262024-02-26Us
US7404489No2004-03-122024-03-12Us
US9415007No2004-07-282024-07-28Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)> 300 °CPhysProp
water solubility12.5 mg/mLhttp://www.hmdb.ca/metabolites/HMDB00607
logP1.897http://www.hmdb.ca/metabolites/HMDB00607
logS-4.5http://www.hmdb.ca/metabolites/HMDB00607
Predicted Properties
PropertyValueSource
logP-14ChemAxon
pKa (Strongest Acidic)1.82ChemAxon
pKa (Strongest Basic)-0.55ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count9ChemAxon
Polar Surface Area440.79 Å2ChemAxon
Rotatable Bond Count16ChemAxon
Refractivity344.12 m3·mol-1ChemAxon
Polarizability134.61 Å3ChemAxon
Number of Rings12ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9574
Blood Brain Barrier-0.7447
Caco-2 permeable-0.6455
P-glycoprotein substrateSubstrate0.8341
P-glycoprotein inhibitor INon-inhibitor0.5082
P-glycoprotein inhibitor IIInhibitor0.6369
Renal organic cation transporterNon-inhibitor0.898
CYP450 2C9 substrateNon-substrate0.8104
CYP450 2D6 substrateNon-substrate0.8085
CYP450 3A4 substrateSubstrate0.65
CYP450 1A2 substrateNon-inhibitor0.8775
CYP450 2C9 inhibitorNon-inhibitor0.8775
CYP450 2D6 inhibitorNon-inhibitor0.8737
CYP450 2C19 inhibitorNon-inhibitor0.7076
CYP450 3A4 inhibitorInhibitor0.7118
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8125
Ames testNon AMES toxic0.5707
CarcinogenicityNon-carcinogens0.7782
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity2.6731 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8988
hERG inhibition (predictor II)Non-inhibitor0.682
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Tetrapyrroles and derivatives
Sub Class
Corrinoids
Direct Parent
Cobalamin derivatives
Alternative Parents
Metallotetrapyrroles / Benzimidazole ribonucleosides and ribonucleotides / Pentose phosphates / Glycosylamines / Monosaccharide phosphates / Benzimidazoles / Phosphoethanolamines / Dialkyl phosphates / Benzenoids / Fatty amides
show 21 more
Substituents
Cobalamin / Metallotetrapyrrole skeleton / 1-ribofuranosylbenzimidazole / Pentose phosphate / Glycosyl compound / N-glycosyl compound / Pentose monosaccharide / Monosaccharide phosphate / Benzimidazole / Phosphoethanolamine
show 45 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cob(III)alamins (CHEBI:17439)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Cofactor
General Function
Zinc ion 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 methyltetrahydrofola...
Gene Name
MTR
Uniprot ID
Q99707
Uniprot Name
Methionine synthase
Molecular Weight
140525.91 Da
References
  1. Stover PJ: Vitamin B12 and older adults. Curr Opin Clin Nutr Metab Care. 2010 Jan;13(1):24-7. doi: 10.1097/MCO.0b013e328333d157. [PubMed:19904199]
  2. Allen LH: Causes of vitamin B12 and folate deficiency. Food Nutr Bull. 2008 Jun;29(2 Suppl):S20-34; discussion S35-7. [PubMed:18709879]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Cofactor
General Function
Modified amino acid binding
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
Uniprot Name
Methylmalonyl-CoA mutase, mitochondrial
Molecular Weight
83133.755 Da
References
  1. Worgan LC, Niles K, Tirone JC, Hofmann A, Verner A, Sammak A, Kucic T, Lepage P, Rosenblatt DS: Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype. Hum Mutat. 2006 Jan;27(1):31-43. [PubMed:16281286]
  2. Brooks AJ, Vlasie M, Banerjee R, Brunold TC: Co-C bond activation in methylmalonyl-CoA mutase by stabilization of the post-homolysis product Co2+ cobalamin. J Am Chem Soc. 2005 Nov 30;127(47):16522-8. [PubMed:16305240]
  3. Kozlowski PM, Andruniow T, Jarzecki AA, Zgierski MZ, Spiro TG: DFT analysis of co-alkyl and co-adenosyl vibrational modes in B12-cofactors. Inorg Chem. 2006 Jul 10;45(14):5585-90. [PubMed:16813422]
  4. Moras E, Hosack A, Watkins D, Rosenblatt DS: Mitochondrial vitamin B12-binding proteins in patients with inborn errors of cobalamin metabolism. Mol Genet Metab. 2007 Feb;90(2):140-7. Epub 2006 Sep 29. [PubMed:17011224]
  5. Stover PJ: Vitamin B12 and older adults. Curr Opin Clin Nutr Metab Care. 2010 Jan;13(1):24-7. doi: 10.1097/MCO.0b013e328333d157. [PubMed:19904199]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Cofactor
General Function
Oxidoreductase activity, oxidizing metal ions, nad or nadp as acceptor
Specific Function
Involved in the reductive regeneration of cob(I)alamin (vitamin B12) cofactor required for the maintenance of methionine synthase in a functional state. Necessary for utilization of methylgroups fr...
Gene Name
MTRR
Uniprot ID
Q9UBK8
Uniprot Name
Methionine synthase reductase
Molecular Weight
80409.22 Da
References
  1. O'Leary VB, Mills JL, Pangilinan F, Kirke PN, Cox C, Conley M, Weiler A, Peng K, Shane B, Scott JM, Parle-McDermott A, Molloy AM, Brody LC: Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association. Mol Genet Metab. 2005 Jul;85(3):220-7. Epub 2005 Mar 17. [PubMed:15979034]
  2. Gueant-Rodriguez RM, Juilliere Y, Candito M, Adjalla CE, Gibelin P, Herbeth B, Van Obberghen E, Gueant JL: Association of MTRRA66G polymorphism (but not of MTHFR C677T and A1298C, MTRA2756G, TCN C776G) with homocysteine and coronary artery disease in the French population. Thromb Haemost. 2005 Sep;94(3):510-5. [PubMed:16268464]
  3. Miriuka SG, Langman LJ, Evrovski J, Miner SE, D'Mello N, Delgado DH, Wong BY, Ross HJ, Cole DE: Genetic polymorphisms predisposing to hyperhomocysteinemia in cardiac transplant patients. Transpl Int. 2005 Jan;18(1):29-35. [PubMed:15612980]
  4. Berkun Y, Abou Atta I, Rubinow A, Orbach H, Levartovsky D, Aamar S, Arbel O, Dresner-Pollak R, Friedman G, Ben-Yehuda A: 2756GG genotype of methionine synthase reductase gene is more prevalent in rheumatoid arthritis patients treated with methotrexate and is associated with methotrexate-induced nodulosis. J Rheumatol. 2007 Aug;34(8):1664-9. Epub 2007 Jul 1. [PubMed:17611986]
  5. van der Linden IJ, den Heijer M, Afman LA, Gellekink H, Vermeulen SH, Kluijtmans LA, Blom HJ: The methionine synthase reductase 66A>G polymorphism is a maternal risk factor for spina bifida. J Mol Med (Berl). 2006 Dec;84(12):1047-54. Epub 2006 Oct 6. [PubMed:17024475]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Cofactor
General Function
Hydrolase activity
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
Uniprot Name
Methylmalonic aciduria type A protein, mitochondrial
Molecular Weight
46537.865 Da
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, Dobson CM, Wai T, Watkins D, Tirone JC, Leclerc D, Dore C, Lepage P, Gravel RA, Rosenblatt DS: Mutations in the MMAA gene in patients with the cblA disorder of vitamin B12 metabolism. Hum Mutat. 2004 Dec;24(6):509-16. [PubMed:15523652]
  4. Dobson CM, Gradinger A, Longo N, Wu X, Leclerc D, Lerner-Ellis J, Lemieux M, Belair C, Watkins D, Rosenblatt DS, Gravel RA: Homozygous nonsense mutation in the MCEE gene and siRNA suppression of methylmalonyl-CoA epimerase expression: a novel cause of mild methylmalonic aciduria. Mol Genet Metab. 2006 Aug;88(4):327-33. Epub 2006 May 11. [PubMed:16697227]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Cofactor
General Function
Cobalamin binding
Specific Function
May be involved in the binding and intracellular trafficking of cobalamin (vitamin B12).
Gene Name
MMACHC
Uniprot ID
Q9Y4U1
Uniprot Name
Methylmalonic aciduria and homocystinuria type C protein
Molecular Weight
31728.095 Da
References
  1. Chandler RJ, Aswani V, Tsai MS, Falk M, Wehrli N, Stabler S, Allen R, Sedensky M, Kazazian HH, Venditti CP: Propionyl-CoA and adenosylcobalamin metabolism in Caenorhabditis elegans: evidence for a role of methylmalonyl-CoA epimerase in intermediary metabolism. Mol Genet Metab. 2006 Sep-Oct;89(1-2):64-73. Epub 2006 Jul 14. [PubMed:16843692]
  2. Ben-Omran TI, Wong H, Blaser S, Feigenbaum A: Late-onset cobalamin-C disorder: a challenging diagnosis. Am J Med Genet A. 2007 May 1;143A(9):979-84. [PubMed:17431913]
  3. Morel CF, Lerner-Ellis JP, Rosenblatt DS: Combined methylmalonic aciduria and homocystinuria (cblC): phenotype-genotype correlations and ethnic-specific observations. Mol Genet Metab. 2006 Aug;88(4):315-21. Epub 2006 May 22. [PubMed:16714133]
  4. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Cofactor
General Function
Protein complex binding
Specific Function
Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.
Gene Name
MTHFR
Uniprot ID
P42898
Uniprot Name
Methylenetetrahydrofolate reductase
Molecular Weight
74595.895 Da
References
  1. Nakamura T, Saionji K, Hiejima Y, Hirayama H, Tago K, Takano H, Tajiri M, Hayashi K, Kawabata M, Funamizu M, Makita Y, Hata A: Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients. Am J Kidney Dis. 2002 May;39(5):1032-9. [PubMed:11979347]
  2. Erdogan MO, Yildiz SH, Solak M, Eser O, Cosar E, Eser B, Koken R, Buyukbas S: C677T polymorphism of the methylenetetrahydrofolate reductase gene does not affect folic acid, vitamin B12, and homocysteine serum levels in Turkish children with neural tube defects. Genet Mol Res. 2010 Jun 22;9(2):1197-203. doi: 10.4238/vol9-2gmr816. [PubMed:20589617]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Cob(i)yrinic acid a,c-diamide adenosyltransferase activity
Specific Function
Not Available
Gene Name
MMAB
Uniprot ID
Q96EY8
Uniprot Name
Cob(I)yrinic acid a,c-diamide adenosyltransferase, mitochondrial
Molecular Weight
27387.975 Da
References
  1. Zhang J, Dobson CM, Wu X, Lerner-Ellis J, Rosenblatt DS, Gravel RA: Impact of cblB mutations on the function of ATP:cob(I)alamin adenosyltransferase in disorders of vitamin B12 metabolism. Mol Genet Metab. 2006 Apr;87(4):315-22. Epub 2006 Jan 24. [PubMed:16439175]
  2. Lerner-Ellis JP, Gradinger AB, Watkins D, Tirone JC, Villeneuve A, Dobson CM, Montpetit A, Lepage P, Gravel RA, Rosenblatt DS: Mutation and biochemical analysis of patients belonging to the cblB complementation class of vitamin B12-dependent methylmalonic aciduria. Mol Genet Metab. 2006 Mar;87(3):219-25. Epub 2006 Jan 10. [PubMed:16410054]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inducer
General Function
Modified amino acid binding
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
Uniprot Name
Methylmalonyl-CoA mutase, mitochondrial
Molecular Weight
83133.755 Da
References
  1. Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency [Link]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inducer
General Function
Zinc ion 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 methyltetrahydrofola...
Gene Name
MTR
Uniprot ID
Q99707
Uniprot Name
Methionine synthase
Molecular Weight
140525.91 Da
References
  1. Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency [Link]
Kind
Protein
Organism
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Pharmacological action
Unknown
General Function
Gtp binding
Specific Function
Catalyzes ATP-dependent phosphorylation of adenosylcobinamide and addition of GMP to adenosylcobinamide phosphate.
Gene Name
cobU
Uniprot ID
Q05599
Uniprot Name
Bifunctional adenosylcobalamin biosynthesis protein CobU
Molecular Weight
19901.7 Da

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Carrier
General Function
Metal ion binding
Specific Function
Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells.
Gene Name
TCN2
Uniprot ID
P20062
Uniprot Name
Transcobalamin-2
Molecular Weight
47534.54 Da
References
  1. Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Receptor binding
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 underlyin...
Gene Name
AMN
Uniprot ID
Q9BXJ7
Uniprot Name
Protein amnionless
Molecular Weight
47753.91 Da
References
  1. Al-Alami JR, Tanner SM, Tayeh MK, de la Chapelle A, El-Shanti H: Homozygous AMN mutation in hereditary selective intestinal malabsorption of vitamin B12 in Jordan. Saudi Med J. 2005 Jul;26(7):1061-4. [PubMed:16047053]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Cobalamin binding
Specific Function
Binds vitamin B12 with femtomolar affinity and protects it from the acidic environment of the stomach.
Gene Name
TCN1
Uniprot ID
P20061
Uniprot Name
Transcobalamin-1
Molecular Weight
48206.32 Da
References
  1. Carmel R: Haptocorrin (transcobalamin I) and cobalamin deficiencies. Clin Chem. 2007 Feb;53(2):367-8; author reply 368-9. [PubMed:17259255]
  2. Al-Alami JR, Tanner SM, Tayeh MK, de la Chapelle A, El-Shanti H: Homozygous AMN mutation in hereditary selective intestinal malabsorption of vitamin B12 in Jordan. Saudi Med J. 2005 Jul;26(7):1061-4. [PubMed:16047053]
  3. Russell-Jones GJ, Alpers DH: Vitamin B12 transporters. Pharm Biotechnol. 1999;12:493-520. [PubMed:10742986]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Metal ion binding
Specific Function
Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells.
Gene Name
TCN2
Uniprot ID
P20062
Uniprot Name
Transcobalamin-2
Molecular Weight
47534.54 Da
References
  1. Chen X, Remacha AF, Sarda MP, Carmel R: Influence of cobalamin deficiency compared with that of cobalamin absorption on serum holo-transcobalamin II. Am J Clin Nutr. 2005 Jan;81(1):110-4. [PubMed:15640468]
  2. Alessio AC, Hoehr NF, Siqueira LH, Bydlowski SP, Annichino-Bizzacchi JM: Polymorphism C776G in the transcobalamin II gene and homocysteine, folate and vitamin B12 concentrations. Association with MTHFR C677T and A1298C and MTRR A66G polymorphisms in healthy children. Thromb Res. 2007;119(5):571-7. Epub 2006 Jul 3. [PubMed:16820193]
  3. Bowen RA, Drake SK, Vanjani R, Huey ED, Grafman J, Horne MK 3rd: Markedly increased vitamin B12 concentrations attributable to IgG-IgM-vitamin B12 immune complexes. Clin Chem. 2006 Nov;52(11):2107-14. [PubMed:17068171]
  4. Bosco P, Gueant-Rodriguez RM, Anello G, Spada R, Romano A, Fajardo A, Caraci F, Ferri R, Gueant JL: Association of homocysteine (but not of MTHFR 677 C>T, MTR 2756 A>G, MTRR 66 A>G and TCN2 776 C>G) with ischaemic cerebrovascular disease in Sicily. Thromb Haemost. 2006 Aug;96(2):154-9. [PubMed:16894458]
  5. Al-Alami JR, Tanner SM, Tayeh MK, de la Chapelle A, El-Shanti H: Homozygous AMN mutation in hereditary selective intestinal malabsorption of vitamin B12 in Jordan. Saudi Med J. 2005 Jul;26(7):1061-4. [PubMed:16047053]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Cobalamin binding
Specific Function
Promotes absorption of the essential vitamin cobalamin (Cbl) in the ileum. After interaction with CUBN, the GIF-cobalamin complex is internalized via receptor-mediated endocytosis.
Gene Name
GIF
Uniprot ID
P27352
Uniprot Name
Gastric intrinsic factor
Molecular Weight
45415.67 Da
References
  1. Fedosov SN, Fedosova NU, Berglund L, Moestrup SK, Nexo E, Petersen TE: Composite organization of the cobalamin binding and cubilin recognition sites of intrinsic factor. Biochemistry. 2005 Mar 8;44(9):3604-14. [PubMed:15736970]
  2. He Q, Madsen M, Kilkenney A, Gregory B, Christensen EI, Vorum H, Hojrup P, Schaffer AA, Kirkness EF, Tanner SM, de la Chapelle A, Giger U, Moestrup SK, Fyfe JC: Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo. Blood. 2005 Aug 15;106(4):1447-53. Epub 2005 Apr 21. [PubMed:15845892]
  3. Moestrup SK: New insights into carrier binding and epithelial uptake of the erythropoietic nutrients cobalamin and folate. Curr Opin Hematol. 2006 May;13(3):119-23. [PubMed:16567952]
  4. Seetharam B: Receptor-mediated endocytosis of cobalamin (vitamin B12). Annu Rev Nutr. 1999;19:173-95. doi: 10.1146/annurev.nutr.19.1.173. [PubMed:10448521]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
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...
Gene Name
CUBN
Uniprot ID
O60494
Uniprot Name
Cubilin
Molecular Weight
398732.93 Da
References
  1. Fedosov SN, Fedosova NU, Berglund L, Moestrup SK, Nexo E, Petersen TE: Composite organization of the cobalamin binding and cubilin recognition sites of intrinsic factor. Biochemistry. 2005 Mar 8;44(9):3604-14. [PubMed:15736970]
  2. He Q, Madsen M, Kilkenney A, Gregory B, Christensen EI, Vorum H, Hojrup P, Schaffer AA, Kirkness EF, Tanner SM, de la Chapelle A, Giger U, Moestrup SK, Fyfe JC: Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo. Blood. 2005 Aug 15;106(4):1447-53. Epub 2005 Apr 21. [PubMed:15845892]
  3. Moestrup SK: New insights into carrier binding and epithelial uptake of the erythropoietic nutrients cobalamin and folate. Curr Opin Hematol. 2006 May;13(3):119-23. [PubMed:16567952]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Carrier
General Function
Zinc ion 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 methyltetrahydrofola...
Gene Name
MTR
Uniprot ID
Q99707
Uniprot Name
Methionine synthase
Molecular Weight
140525.91 Da
References
  1. Vitamin B12 transport proteins: crystallographic analysis of beta-axial ligand substitutions in cobalamin bound to transcobalamin [Link]

Drug created on June 13, 2005 07:24 / Updated on July 13, 2018 00:56