Cyanocobalamin - Revision history

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References

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	~~== References ==~~
	~~{{reflist\|refs=~~

	<ref name=PMC2809139>{{cite journal \| vauthors = Quadros EV \| title = Advances in the understanding of cobalamin assimilation and metabolism \| journal = British Journal of Haematology \| volume = 148 \| issue = 2 \| pages = 195–204 \| date = January 2010 \| pmid = 19832808 \| pmc = 2809139 \| doi = 10.1111/j.1365-2141.2009.07937.x }}</ref>

	<ref name="MechB12">{{cite book \| vauthors = Dolphin D \| title = [205] Preparation of the reduced forms of vitamin B12 and of some analogs of the vitamin B12 coenzyme containing a cobalt-carbon bond. \| chapter = [205] Preparation of the reduced forms of vitamin B12 and of some analogs of the vitamin B12 coenzyme containing a cobalt-carbon bond \| series = Methods in Enzymology \| date = January 1971 \| volume = 18 \| pages = 34–52 \| publisher = Academic Press \| veditors = McCormick DB, Wright LD \| doi = 10.1016/S0076-6879(71)18006-8 \| isbn = 9780121818821 }}</ref>

	<ref name="InnoCatalyst">{{cite journal \| vauthors = Brodie JD \| title = On the mechanism of catalysis by vitamin B12 \| journal = Proceedings of the National Academy of Sciences of the United States of America \| volume = 62 \| issue = 2 \| pages = 461–467 \| date = February 1969 \| pmid = 5256224 \| pmc = 277821 \| doi = 10.1073/pnas.62.2.461 \| doi-access = free \| bibcode = 1969PNAS...62..461B }}</ref>

	<ref name="Catalysis">{{cite journal\|vauthors=Shimakoshi H, Hisaeda Y\|url=http://www.tciamerica.com/tcimail/backnumber/article/138drE.pdf\|title=Environmental-friendly catalysts learned from Vitamin {{chem\|B\|12}}-dependent enzymes\|page=2\|journal=Tcimail\|volume=128}}{{Dead link\|date=January 2023 \|bot=InternetArchiveBot \|fix-attempted=yes }}</ref>

	<ref name=Riaz>{{cite journal\|vauthors=Riaz M, Ansari ZA, Iqbal F, Akram M\|title=Microbial production of vitamin B12 by methanol utilizing strain of Pseudomonas specie\|journal=Pak J. Biochem. Mol. Biol\|year=2007\|volume=40\|pages=5–10\|url=https://pu-pk.academia.edu/MuhammadAkram/Papers/83315/Microbial_production_of_vitamin_B12_by_methanol_utilizing_strain_of\|access-date=31 October 2017\|archive-date=25 April 2012\|archive-url=https://web.archive.org/web/20120425162917/http://pu-pk.academia.edu/MuhammadAkram/Papers/83315/Microbial_production_of_vitamin_B12_by_methanol_utilizing_strain_of\|url-status=dead}}</ref>

	<ref name = herbert>{{cite journal \| vauthors = Herbert V \| title = Vitamin B-12: plant sources, requirements, and assay \| journal = The American Journal of Clinical Nutrition \| volume = 48 \| issue = 3 Suppl \| pages = 852–858 \| date = September 1988 \| pmid = 3046314 \| doi = 10.1093/ajcn/48.3.852 }}</ref>

	<!-- unused ref <ref name=Ullmann>{{cite book\| vauthors = Blum R \| chapter = Vitamins, 11. Niacin (nicotinic acid, nicotinamide) \| title = Ullmann's Encyclopedia of Industrial Chemistry \| date = June 2000 \| pages = 1–9 \| doi=10.1002/14356007.a27_443 \|isbn=3527306730}}</ref>-->

	~~<ref name=umm>[https://web.archive.org/web/20070514204818/http://www.umm.edu/altmed/drugs/cyanocobalamin-033700.htm Cyanocobalamin]. University of Maryland Medical Center</ref>~~

	<!--unused<ref name=Sides>{{cite web\|title=Cyanocobalamin (Cyanocobalamin 50microgram tablets). Side effects\|url=http://www.nhs.uk/medicine-guides/pages/MedicineSideEffects.aspx?condition=Anaemia%20(B12%20deficient)&medicine=cyanocobalamin&preparation=Cyanocobalamin%2050microgram%20tablets\|website=NHS Choices\|access-date=4 July 2015\|archive-url=https://web.archive.org/web/20150704172930/http://www.nhs.uk/medicine-guides/pages/MedicineSideEffects.aspx?condition=Anaemia%20(B12%20deficient)&medicine=cyanocobalamin&preparation=Cyanocobalamin%2050microgram%20tablets\|archive-date=4 July 2015}}</ref>-->

	<ref name=Sides2>{{cite web\|title=Cyanocobalamin Injection\|url=https://www.nlm.nih.gov/medlineplus/druginfo/meds/a605007.html\|website=MedlinePlus\|access-date=4 July 2015\|archive-url=https://web.archive.org/web/20150419093329/https://www.nlm.nih.gov/medlineplus/druginfo/meds/a605007.html\|archive-date=19 April 2015}}</ref>

	<ref name=Anemia>{{cite web\|title=Clinical Vitamin B12 Deficiency. Managing Patients\|url=https://www.cdc.gov/ncbddd/b12/patients.html\|website=Centers for Disease Control and Prevention\|access-date=4 July 2015\|archive-url=https://web.archive.org/web/20150426052222/http://www.cdc.gov/ncbddd/b12/patients.html\|archive-date=26 April 2015}}</ref>

	<ref name=blind>{{cite web\|title=Vitamin B12\|url=https://www.nlm.nih.gov/medlineplus/druginfo/natural/926.html\|website=MedlinePlus\|access-date=4 July 2015\|archive-url=https://web.archive.org/web/20150405050708/https://www.nlm.nih.gov/medlineplus/druginfo/natural/926.html\|archive-date=5 April 2015}}</ref>

	<ref name=Hannibal>{{cite journal \| vauthors = Hannibal L, Kim J, Brasch NE, Wang S, Rosenblatt DS, Banerjee R, Jacobsen DW \| title = Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product \| journal = Molecular Genetics and Metabolism \| volume = 97 \| issue = 4 \| pages = 260–266 \| date = August 2009 \| pmid = 19447654 \| pmc = 2709701 \| doi = 10.1016/j.ymgme.2009.04.005 }}</ref>

	<ref name=Watanabe>{{cite book \| vauthors = Watanabe F, Nakano Y \| title = Vitamins and Coenzymes Part K \| chapter = Purification and characterization of aquacobalamin reductases from mammals \| series = Methods in Enzymology \| volume = 281 \| pages = 295–305 \| year = 1997 \| pmid = 9250994 \| doi = 10.1016/S0076-6879(97)81036-1 \| isbn = 9780121821821 }}</ref>

	<ref name="Quadros">{{Cite book \|last=Quadros \|first=E. V. \|url=https://www.degruyter.com/document/doi/10.1515/9783111510828-118/html \|title=Interconversion of cobalamins in human lymphocytes in vitro and the influence of nitrous oxide on synthesis of cobalamin coenzymes \|last2=Jackson \|first2=Beverley \|last3=Hoffbrand \|first3=A. V. \|last4=Linnell \|first4=J. C. \|date=8 October 2019 \|work=Vitamin B12, Proceedings of the Third European Symposium on Vitamin B12 and Intrinsic Factor. \|publisher=De Gruyter \|isbn=978-3-11-151082-8 \|pages=1045–1054 \|language=en \|doi=10.1515/9783111510828-118}}</ref>

	<ref name=DSM-fortify>{{cite web\|title=DSM in Food, Beverages & Dietary Supplements\|url=http://www.dsm.com/markets/foodandbeverages/en_US/products/vitamins/vitamin-b12.html \|publisher=DSM\|access-date=2 March 2015}}</ref>

	<ref name=Watanabe2>{{cite journal \| vauthors = Watanabe F, Abe K, Fujita T, Goto M, Hiemori M, Nakano Y \| title = Effects of Microwave Heating on the Loss of Vitamin B(12) in Foods \| journal = Journal of Agricultural and Food Chemistry \| volume = 46 \| issue = 1 \| pages = 206–210 \| date = January 1998 \| pmid = 10554220 \| doi = 10.1021/jf970670x \| s2cid = 23096987 }}</ref>

	<ref name=4REQ>{{cite journal \| vauthors = Mancia F, Evans PR \| title = Conformational changes on substrate binding to methylmalonyl CoA mutase and new insights into the free radical mechanism \| journal = Structure \| volume = 6 \| issue = 6 \| pages = 711–720 \| date = June 1998 \| pmid = 9655823 \| doi = 10.1016/S0969-2126(98)00073-2 \| doi-access = free }}</ref>

	<ref name=1Q8J>{{cite journal \| vauthors = Evans JC, Huddler DP, Hilgers MT, Romanchuk G, Matthews RG, Ludwig ML \| title = Structures of the N-terminal modules imply large domain motions during catalysis by methionine synthase \| journal = Proceedings of the National Academy of Sciences of the United States of America \| volume = 101 \| issue = 11 \| pages = 3729–3736 \| date = March 2004 \| pmid = 14752199 \| pmc = 374312 \| doi = 10.1073/pnas.0308082100 \| doi-access = free \| bibcode = 2004PNAS..101.3729E }}</ref>

	}}

	{{ATC navboxes\|A11\|B03}}		{{ATC navboxes\|A11\|B03}}

Fire: Created page with "{{Short description|Form of vitamin B-12}} {{Infobox drug | image = Cyanocobalamin-b12.png | width = | alt = | caption = Skeletal formula | image2 = Cyanocobalamin-from-xtal-3D-st-noH.png | width2 = | alt2 = | caption2 = Stick model of cyanocobalamin based on the crystal structure | pronounce = sye AN oh koe BAL a mi..."

2024-04-06T02:28:58Z

Created page with "{{Short description|Form of vitamin B-12}} {{Infobox drug | image = Cyanocobalamin-b12.png | width = | alt = | caption = Skeletal formula | image2 = Cyanocobalamin-from-xtal-3D-st-noH.png | width2 = | alt2 = | caption2 = Stick model of cyanocobalamin based on the crystal structure  | pronounce = sye AN oh koe BAL a mi..."

New page

{{Short description|Form of vitamin B-12}}
{{Infobox drug
| image = Cyanocobalamin-b12.png
| width =
| alt =
| caption = [[Skeletal formula]]
| image2 = Cyanocobalamin-from-xtal-3D-st-noH.png
| width2 =
| alt2 =
| caption2 = [[Ball-and-stick model|Stick model]] of cyanocobalamin based on the crystal structure


| pronounce = sye AN oh koe BAL a min
| tradename = Cobolin-M, Depo-Cobolin, others
| Drugs.com = {{drugs.com|ppa|cyanocobalamin}}
| MedlinePlus = a604029
| DailyMedID = Cyanocobalamin
| pregnancy_AU=
| pregnancy_AU_comment = Exempt
| pregnancy_category=
| routes_of_administration = [[By mouth]], [[intramuscular]], [[nasal spray]]
| class =
| ATCvet =
| ATC_prefix = B03
| ATC_suffix = BA01
| ATC_supplemental =


| legal_AU = 
| legal_AU_comment =
| legal_BR = 
| legal_BR_comment =
| legal_CA = 
| legal_CA_comment =
| legal_DE = 
| legal_DE_comment =
| legal_NZ = 
| legal_NZ_comment =
| legal_UK = 
| legal_UK_comment =
| legal_US = OTC
| legal_US_comment = / Rx-only
| legal_UN = 
| legal_UN_comment =
| legal_status = 


| bioavailability =
| protein_bound =
| metabolism =
| metabolites =
| onset =
| elimination_half-life =
| duration_of_action =
| excretion =


| CAS_number = 68-19-9
| CAS_supplemental =
| PubChem = 16212801
| PubChemSubstance =
| IUPHAR_ligand =
| DrugBank = DB00115
| ChemSpiderID = 24921423
| UNII = P6YC3EG204
| KEGG = D00166
| ChEBI =
| ChEMBL = 2110563
| NIAID_ChemDB =
| PDB_ligand =
| synonyms =


| IUPAC_name =
| C=63 | H=88 | Co=1 | N=14 | O=14 | P=1
| SMILES = CC1=CC2=C(C=C1C)N(C=N2)C3C(C(C(O3)CO)OP(=O)([O-])OC(C)CNC(=O)CCC4(C(C5C6(C(C(C(=C(C7=NC(=CC8=NC(=C(C4=N5)C)C(C8(C)C)CCC(=O)N)C(C7(C)CC(=O)N)CCC(=O)N)C)[N-]6)CCC(=O)N)(C)CC(=O)N)C)CC(=O)N)C)O.[C-]#N.[Co+3]
| StdInChI = 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;-1;+3/p-2/t31-,34-,35-,36-,37+,41-,52-,53-,56-,57?,59-,60+,61+,62+;;/m1../s1
| StdInChI_comment =
| StdInChIKey = FDJOLVPMNUYSCM-QJRSUKKJSA-L
| density =
| density_notes =
| melting_point = 300
| melting_high =
| melting_notes = +
| boiling_point = 300
| boiling_notes = +
| solubility = 1/80
| sol_units = g/ml
| specific_rotation =
}}

'''Cyanocobalamin''' is a form of [[Vitamin B12|vitamin {{chem|B|12}}]] used to treat and prevent [[vitamin B12 deficiency|vitamin {{chem|B|12}} deficiency]] except in the presence of cyanide toxicity. The deficiency may occur in [[pernicious anemia]], following [[gastrectomy|surgical removal of the stomach]], with [[fish tapeworm]], or due to [[bowel cancer]]. It is used by mouth, by [[injection into a muscle]], or as a [[nasal spray]].


Cyanocobalamin is generally well tolerated. Minor side effects may include diarrhea, nausea, upset stomach, and itchiness.Serious side effects may include [[anaphylaxis]], and [[low blood potassium]] resulting in [[heart failure]]. Use is not recommended in those who are allergic to [[cobalt]] or have [[Leber's disease]]. No overdosage or toxicity has been reported. It is less preferred than [[hydroxocobalamin]] for treating vitamin {{chem|B|12}} deficiency because it has slightly lower bioavailability. Some study have shown that it has an antihypotensive effect.


Cyanocobalamin was first manufactured in the 1940s. It is available as a [[generic medication]] and [[over the counter]]. In 2021, it was the 110th most commonly prescribed medication in the United States, with more than 5{{nbsp}}million prescriptions.

==Medical use==
Cyanocobalamin is usually prescribed after surgical removal of part or all of the [[stomach]] or [[intestine]] to ensure adequate serum levels of vitamin {{chem|B|12}}. It is also used to treat [[pernicious anemia]], [[Vitamin B12 deficiency|vitamin {{chem|B|12}} deficiency]] (due to low intake from food or inability to absorb due to genetic or other factors), [[thyrotoxicosis]], [[hemorrhage]], [[malignancy]], liver disease and kidney disease. Cyanocobalamin injections are often prescribed to [[gastric bypass]] patients who have had part of their [[small intestine]] bypassed, making it difficult for {{chem|B|12}} to be acquired via food or vitamins. Cyanocobalamin is also used to perform the [[Schilling test]] to check ability to absorb vitamin {{chem|B|12}}.

Cyanocobalamin is also produced in the body (and then excreted via urine) after intravenous [[hydroxycobalamin]] is used to treat [[cyanide poisoning]].

==Side effects==
Possible side effects of cyanocobalamin injection include allergic reactions such as [[hives]], difficult breathing; redness of the face; swelling of the arms, hands, feet, ankles or lower legs; extreme thirst; and [[diarrhea]]. Less-serious side effects may include headache, dizziness, leg pain, [[itching]], or [[rash]].

Treatment of [[megaloblastic anemia]] with concurrent vitamin {{chem|B|12}} deficiency using {{chem|B|12}} vitamers (including cyanocobalamin), creates the possibility of [[hypokalemia]] due to increased [[erythropoiesis]] (red blood cell production) and consequent cellular uptake of [[potassium]] upon anemia resolution. When treated with cyanocobalamin, patients with [[Leber's disease]] may develop serious [[optic atrophy]], possibly leading to blindness.

==Chemistry==
Vitamin {{chem|B|12}} is the "generic descriptor" name for any [[vitamer]]s of vitamin {{chem|B|12}}. Animals, including humans, can convert cyanocobalamin to any one of the active vitamin {{chem|B|12}} compounds.

Cyanocobalamin is one of the most widely manufactured [[vitamer]]s in the vitamin {{chem|B|12}} family (the family of chemicals that function as {{chem|B|12}} when put into the body), because cyanocobalamin is the most air-stable of the {{chem|B|12}} forms. It is the easiest to purify after it is produced by [[bacterial fermentation]]. It can be obtained as dark red crystals or as an amorphous red powder. Cyanocobalamin is [[hygroscopic]] in the [[anhydrous]] form, and sparingly soluble in water (1:80). It is stable to [[autoclaving]] for short periods at {{convert|121|C|F}}. The vitamin {{chem|B|12}} [[coenzymes]] are unstable in light. After consumption the cyanide [[ligand]] is replaced by other groups ([[adenosyl]], [[methyl]]) to produce the biologically active forms. The [[cyanide]] is converted to [[thiocyanate]] and excreted by the kidney.

===Chemical reactions===
[[File:Various reduced forms of Cyanocobalamin.jpg|thumb|Reduced forms of Cyanocobalamin, with a Co(I) (top), Co(II) (middle), and Co(III) (bottom)]]
In the cobalamins, [[cobalt]] normally exists in the trivalent state, Co(III). However, under reducing conditions, the cobalt center is reduced to Co(II) or even Co(I), which are usually denoted as {{chem|B|12r}} and {{chem|B|12s}}, for reduced and super reduced, respectively.

{{chem|B|12r}} and {{chem|B|12s}} can be prepared from cyanocobalamin by controlled potential reduction, or chemical reduction using [[sodium borohydride]] in alkaline solution, [[zinc]] in [[acetic acid]], or by the action of [[thiols]]. Both {{chem|B|12r}} and {{chem|B|12s}} are stable indefinitely under oxygen-free conditions. {{chem|B|12r}} appears orange-brown in solution, while {{chem|B|12s}} appears bluish-green under natural daylight, and purple under artificial light.

{{chem|B|12s}} is one of the most nucleophilic species known in aqueous solution. This property allows the convenient preparation of cobalamin analogs with different [[substituents]], via [[nucleophilic]] attack on [[alkyl halide]]s and vinyl halides.

For example, cyanocobalamin can be converted to its analog cobalamins via reduction to {{chem|B|12s}}, followed by the addition of the corresponding [[alkyl halides]], [[acyl halides]], [[alkene]] or [[alkyne]]. [[Steric hindrance]] is the major limiting factor in the synthesis of the {{chem|B|12}} coenzyme analogs. For example, no reaction occurs between [[neopentyl]] chloride and {{chem|B|12s}}, whereas the secondary alkyl halide analogs are too unstable to be isolated. This effect may be due to the strong coordination between [[benzimidazole]] and the central cobalt atom, pulling it down into the plane of the [[corrin]] ring. The [[trans effect]] determines the polarizability of the Co–C bond so formed. However, once the [[benzimidazole]] is detached from cobalt by quaternization with [[methyl iodide]], it is replaced by {{chem|H|2|O}} or [[hydroxyl]] ions. Various secondary alkyl halides are then readily attacked by the modified {{chem|B|12s}} to give the corresponding stable cobalamin analogs. The products are usually extracted and purified by phenol-methylene chloride extraction or by column chromatography.

Cobalamin analogs prepared by this method include the naturally occurring coenzymes [[methylcobalamin]] and [[cobamamide]], and other cobalamins that do not occur naturally, such as vinylcobalamin, carboxymethylcobalamin and cyclohexylcobalamin. This reaction is under review for use as a catalyst for [[chemical dehalogenation]], organic reagent and photosensitized catalyst systems.

==Production==
Cyanocobalamin is commercially prepared by [[bacterial fermentation]]. Fermentation by a variety of [[microorganism]]s yields a mixture of [[methylcobalamin]], [[hydroxocobalamin]] and [[adenosylcobalamin]]. These compounds are converted to cyanocobalamin by addition of [[potassium cyanide]] in the presence of [[sodium nitrite]] and heat. Since multiple species of ''[[Propionibacterium]]'' produce no [[exotoxin]]s or [[endotoxin]]s and have been granted [[GRAS]] status (generally regarded as safe) by the [[United States Food and Drug Administration]], they are the preferred bacterial fermentation organisms for vitamin {{chem|B|12}} production.

Historically, the physiological form was initially thought to be cyanocobalamin. This was because [[hydroxocobalamin]] produced by bacteria was changed to cyanocobalamin during purification in [[activated charcoal]] columns after separation from the bacterial cultures (because [[cyanide]] is naturally present in activated charcoal). Cyanocobalamin is the form in most pharmaceutical preparations because adding cyanide stabilizes the molecule.

The total world production of vitamin B<sub>12</sub>, by four companies (the French Sanofi-Aventis and three Chinese companies) in 2008 was 35 tonnes.

== Metabolism ==
The two bioactive forms of vitamin {{chem|B|12}} are [[methylcobalamin]] in [[cytosol]] and [[adenosylcobalamin]] in [[mitochondria]]. Multivitamins often contain cyanocobalamin, which is presumably converted to bioactive forms in the body. Both methylcobalamin and adenosylcobalamin are commercially available as supplement pills. The [[MMACHC]] gene product catalyzes the decyanation of cyanocobalamin as well as the dealkylation of alkylcobalamins including methylcobalamin and adenosylcobalamin. This function has also been attributed to [[Cyanocobalamin reductase (cyanide-eliminating)|cobalamin reductases]]. The MMACHC gene product and cobalamin reductases enable the interconversion of cyano- and alkylcobalamins.

Cyanocobalamin is added to fortify nutrition, including baby milk powder, breakfast cereals and [[energy drinks]] for humans, also animal feed for poultry, swine and fish. Vitamin {{chem|B|12}} becomes inactive due to [[hydrogen cyanide]] and [[nitric oxide]] in cigarette smoke. Vitamin {{chem|B|12}} also becomes inactive due to [[nitrous oxide]] {{chem|N|2|O}} commonly known as laughing gas, used for [[anaesthesia]] and as a recreational drug. Vitamin {{chem|B|12}} becomes inactive due to microwaving or other forms of heating.

=== In the cytosol ===
[[Methylcobalamin]] and [[5-methyltetrahydrofolate]] are needed by [[methionine synthase]] in the [[methionine]] cycle to transfer a methyl group from [[5-methyltetrahydrofolate]] to [[homocysteine]], thereby generating [[tetrahydrofolate]] (THF) and [[methionine]], which is used to make [[SAMe]]. [[SAMe]] is the universal methyl donor and is used for [[DNA methylation]] and to make [[lipid bilayer|phospholipid]] [[cell membrane|membranes]], [[choline]], [[sphingomyelin]], [[acetylcholine]], and other [[neurotransmitters]].

=== In mitochondria ===
[[File:Odd-chain FA oxydation.png|thumb|upright|Vitamin {{chem|B|12}} [[adenosylcobalamin]] in [[mitochondrion]]—cholesterol and protein metabolism]]

The enzymes that use {{chem|B|12}} as a built-in cofactor are [[methylmalonyl-CoA mutase]] ([[Protein Data Bank|PDB]] 4REQ) and [[methionine synthase]] ([[Protein Data Bank|PDB]] 1Q8J).

The metabolism of [[propionyl-CoA]] occurs in the mitochondria and requires Vitamin {{chem|B|12}} (as [[adenosylcobalamin]]) to make [[succinyl-CoA]]. When the conversion of propionyl-CoA to succinyl-CoA in the mitochondria fails due to Vitamin {{chem|B|12}} deficiency, elevated blood levels of [[methylmalonic acid]] (MMA) occur. Thus, elevated blood levels of [[homocysteine]] and MMA may both be indicators of [[vitamin B12 deficiency|vitamin {{chem|B|12}} deficiency]].

[[Adenosylcobalamin]] is needed as [[cofactor (biochemistry)|cofactor]] in [[methylmalonyl-CoA mutase]]—MUT enzyme. Processing of cholesterol and protein gives [[propionyl-CoA]] that is converted to [[methylmalonyl-CoA]], which is used by [[methylmalonyl-CoA mutase|MUT enzyme]] to make [[succinyl-CoA]]. Vitamin {{chem|B|12}} is needed to prevent anemia, since making [[porphyrin]] and [[heme]] in [[mitochondria]] for producing hemoglobin in red blood cells depends on [[succinyl-CoA]] made by vitamin {{chem|B|12}}.

=== Absorption and transport ===
Inadequate absorption of vitamin {{chem|B|12}} may be related to [[coeliac disease]]. Intestinal absorption of vitamin {{chem|B|12}} requires successively three different protein molecules: [[haptocorrin]], [[intrinsic factor]] and [[transcobalamin II]].

== See also ==
* [[Methylcobalamin]]
* [[Hydroxocobalamin]]
* [[Adenosylcobalamin]]
* [[Cobalamin biosynthesis]]

{{-}}

== References ==
{{reflist|refs=

<ref name=PMC2809139>{{cite journal | vauthors = Quadros EV | title = Advances in the understanding of cobalamin assimilation and metabolism | journal = British Journal of Haematology | volume = 148 | issue = 2 | pages = 195–204 | date = January 2010 | pmid = 19832808 | pmc = 2809139 | doi = 10.1111/j.1365-2141.2009.07937.x }}</ref>

<ref name="MechB12">{{cite book | vauthors = Dolphin D | title = [205] Preparation of the reduced forms of vitamin B12 and of some analogs of the vitamin B12 coenzyme containing a cobalt-carbon bond. | chapter = [205] Preparation of the reduced forms of vitamin B12 and of some analogs of the vitamin B12 coenzyme containing a cobalt-carbon bond | series = Methods in Enzymology | date = January 1971 | volume = 18 | pages = 34–52 | publisher = Academic Press | veditors = McCormick DB, Wright LD | doi = 10.1016/S0076-6879(71)18006-8 | isbn = 9780121818821 }}</ref>

<ref name="InnoCatalyst">{{cite journal | vauthors = Brodie JD | title = On the mechanism of catalysis by vitamin B12 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 62 | issue = 2 | pages = 461–467 | date = February 1969 | pmid = 5256224 | pmc = 277821 | doi = 10.1073/pnas.62.2.461 | doi-access = free | bibcode = 1969PNAS...62..461B }}</ref>

<ref name="Catalysis">{{cite journal|vauthors=Shimakoshi H, Hisaeda Y|url=http://www.tciamerica.com/tcimail/backnumber/article/138drE.pdf|title=Environmental-friendly catalysts learned from Vitamin {{chem|B|12}}-dependent enzymes|page=2|journal=Tcimail|volume=128}}{{Dead link|date=January 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>

<ref name=Riaz>{{cite journal|vauthors=Riaz M, Ansari ZA, Iqbal F, Akram M|title=Microbial production of vitamin B12 by methanol utilizing strain of Pseudomonas specie|journal=Pak J. Biochem. Mol. Biol|year=2007|volume=40|pages=5–10|url=https://pu-pk.academia.edu/MuhammadAkram/Papers/83315/Microbial_production_of_vitamin_B12_by_methanol_utilizing_strain_of|access-date=31 October 2017|archive-date=25 April 2012|archive-url=https://web.archive.org/web/20120425162917/http://pu-pk.academia.edu/MuhammadAkram/Papers/83315/Microbial_production_of_vitamin_B12_by_methanol_utilizing_strain_of|url-status=dead}}</ref>

<ref name = herbert>{{cite journal | vauthors = Herbert V | title = Vitamin B-12: plant sources, requirements, and assay | journal = The American Journal of Clinical Nutrition | volume = 48 | issue = 3 Suppl | pages = 852–858 | date = September 1988 | pmid = 3046314 | doi = 10.1093/ajcn/48.3.852 }}</ref>



<ref name=umm>[https://web.archive.org/web/20070514204818/http://www.umm.edu/altmed/drugs/cyanocobalamin-033700.htm Cyanocobalamin]. University of Maryland Medical Center</ref>



<ref name=Sides2>{{cite web|title=Cyanocobalamin Injection|url=https://www.nlm.nih.gov/medlineplus/druginfo/meds/a605007.html|website=MedlinePlus|access-date=4 July 2015|archive-url=https://web.archive.org/web/20150419093329/https://www.nlm.nih.gov/medlineplus/druginfo/meds/a605007.html|archive-date=19 April 2015}}</ref>

<ref name=Anemia>{{cite web|title=Clinical Vitamin B12 Deficiency. Managing Patients|url=https://www.cdc.gov/ncbddd/b12/patients.html|website=Centers for Disease Control and Prevention|access-date=4 July 2015|archive-url=https://web.archive.org/web/20150426052222/http://www.cdc.gov/ncbddd/b12/patients.html|archive-date=26 April 2015}}</ref>

<ref name=blind>{{cite web|title=Vitamin B12|url=https://www.nlm.nih.gov/medlineplus/druginfo/natural/926.html|website=MedlinePlus|access-date=4 July 2015|archive-url=https://web.archive.org/web/20150405050708/https://www.nlm.nih.gov/medlineplus/druginfo/natural/926.html|archive-date=5 April 2015}}</ref>

<ref name=Hannibal>{{cite journal | vauthors = Hannibal L, Kim J, Brasch NE, Wang S, Rosenblatt DS, Banerjee R, Jacobsen DW | title = Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product | journal = Molecular Genetics and Metabolism | volume = 97 | issue = 4 | pages = 260–266 | date = August 2009 | pmid = 19447654 | pmc = 2709701 | doi = 10.1016/j.ymgme.2009.04.005 }}</ref>

<ref name=Watanabe>{{cite book | vauthors = Watanabe F, Nakano Y | title = Vitamins and Coenzymes Part K | chapter = Purification and characterization of aquacobalamin reductases from mammals | series = Methods in Enzymology | volume = 281 | pages = 295–305 | year = 1997 | pmid = 9250994 | doi = 10.1016/S0076-6879(97)81036-1 | isbn = 9780121821821 }}</ref>

<ref name="Quadros">{{Cite book |last=Quadros |first=E. V. |url=https://www.degruyter.com/document/doi/10.1515/9783111510828-118/html |title=Interconversion of cobalamins in human lymphocytes in vitro and the influence of nitrous oxide on synthesis of cobalamin coenzymes |last2=Jackson |first2=Beverley |last3=Hoffbrand |first3=A. V. |last4=Linnell |first4=J. C. |date=8 October 2019 |work=Vitamin B12, Proceedings of the Third European Symposium on Vitamin B12 and Intrinsic Factor. |publisher=De Gruyter |isbn=978-3-11-151082-8 |pages=1045–1054 |language=en |doi=10.1515/9783111510828-118}}</ref>

<ref name=DSM-fortify>{{cite web|title=DSM in Food, Beverages & Dietary Supplements|url=http://www.dsm.com/markets/foodandbeverages/en_US/products/vitamins/vitamin-b12.html |publisher=DSM|access-date=2 March 2015}}</ref>

<ref name=Watanabe2>{{cite journal | vauthors = Watanabe F, Abe K, Fujita T, Goto M, Hiemori M, Nakano Y | title = Effects of Microwave Heating on the Loss of Vitamin B(12) in Foods | journal = Journal of Agricultural and Food Chemistry | volume = 46 | issue = 1 | pages = 206–210 | date = January 1998 | pmid = 10554220 | doi = 10.1021/jf970670x | s2cid = 23096987 }}</ref>

<ref name=4REQ>{{cite journal | vauthors = Mancia F, Evans PR | title = Conformational changes on substrate binding to methylmalonyl CoA mutase and new insights into the free radical mechanism | journal = Structure | volume = 6 | issue = 6 | pages = 711–720 | date = June 1998 | pmid = 9655823 | doi = 10.1016/S0969-2126(98)00073-2 | doi-access = free }}</ref>

<ref name=1Q8J>{{cite journal | vauthors = Evans JC, Huddler DP, Hilgers MT, Romanchuk G, Matthews RG, Ludwig ML | title = Structures of the N-terminal modules imply large domain motions during catalysis by methionine synthase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 11 | pages = 3729–3736 | date = March 2004 | pmid = 14752199 | pmc = 374312 | doi = 10.1073/pnas.0308082100 | doi-access = free | bibcode = 2004PNAS..101.3729E }}</ref>

}}

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[[Category:B vitamins]]
[[Category:Organocobalt compounds]]
[[Category:Cofactors]]
[[Category:Vitamin B12]]
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