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The NuGOwiki Metabolite Database is a joint initiative of NuGO and HMDB
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| Vitamin B12 | ||||||
|---|---|---|---|---|---|---|
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| Chemical Name | Vitamin B12 | |||||
| Chemical Formula | C63H89CoN14O14P | |||||
| CAS Number | 68-19-9 | |||||
| Chemical Information | HMDB00607 | |||||
| Biochemical Taxonomy |
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| Functional Taxonomy | Not Available | |||||
| Nutritional Taxonomy | Not Available | |||||
| Metabolic Pathways | Not Available | |||||
| Biofluid Location |
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| Tissue Location |
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| Normal Biofluid Concentrations |
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| Normal Tissue Concentrations | Not Available | |||||
| Diseases / Conditions Related to Nutrition |
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| Other (Monogenic Disorders) | Not Available | |||||
| Abnormal Biofluid Concentrations |
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| Abnormal Tissue Concentrations | Not Available | |||||
| Physiological Processes | Not Available | |||||
| Authors: | |
| Affiliations: |
Contents |
Introduction
guidelines
[from wikipedia] Vitamin B-12, known also as vitamin B12 (or commonly B12 or B-12 for short), is a collection of cobalt and corrin-ring molecules which are defined by their particular vitamin function in the body. All of the substrate cobalt-corrin molecules from which B-12 is made must be synthesized by bacteria. However, after this synthesis is complete, the body has a limited power to convert any form of B-12 to another, by means of enzymatically removing certain prosthetic chemical groups from the cobalt atom.
Cyanocobalamin is one such compound that is metabolized to a vitamin in this B complex. However, this form of B-12 does not occur in nature normally, but is a byproduct of the fact that other forms of B-12 are avid binders of cyanide (-CN) which they pick up in the process of activated charcoal purification of the vitamin after it is made by bacteria in the commercial process. Since the cyanocobalamin form of B-12 is deeply red colored, easy to crystallize, and is not sensitive to air-oxidation, it is typically used as a form of B-12 for food additives and in many common multivitamins. However, this form is not perfectly synonymous with B-12, inasmuch as many subtances have B-12 vitamin activity and can properly be labeled vitamin B-12, but cyanocobalamin is just one of them. (Thus, all cyanocobalmin is vitamin B-12, but not all vitamin B-12 is cyanocobalamin). [1]
Vitamin B-12 is important for the normal functioning of the brain and nervous system and for the formation of blood. It is normally involved in the metabolism of every cell of the body, especially affecting the DNA synthesis and regulation but also fatty acid synthesis and energy production. However, many (though not all) of the effects of functions of B-12 can be replaced by sufficient quantities of folate(another B vitamin), since B-12 is used to regenerate folate in the body. Most "B-12 deficient symptoms" are actually folate deficient symptoms, since they include all the effects of pernicious anemia and megaloblastosis, which are due to poor synthesis of DNA when the body does not have a proper supply of folate for the production of thymine. When sufficient folate is available, all known B-12 functions save those connected with homocysteine, normalize
B12 is the most chemically complex of all the vitamins. B12's structure is based on a corrin ring, which, although similar to the porphyrin ring found in heme, chlorophyll, and cytochrome, has two of the pyrrole rings directly bonded. The central metal ion is Co (cobalt). B12 cannot be made by plants or by animal<span class="plainlinks"irritable bowel syndrome/span> as the only type of organisms that have the enzymes required for the synthesis of B12 are bacteria and archaea. Higher plants do not concentrate vitamin B 12 from the soil and so are a poor source of the substance as compared with animal tissues. Vitamin B12 is naturally found in foods including meat (especially liver and shellfish), eggs, and milk products.
Biological Function
guidelines
[from wikipedia]
Functions
Coenzyme B-12's reactive C-Co bond participates in two types of enzyme-catalyzed reactions:
- Rearrangements in which a hydrogen atom is directly transferred between two adjacent atoms with concomitant exchange of the second substituent, X, which may be a carbon atom with substituents, an oxygen atom of an alcohol, or an amine.
- Methyl (-CH3) group transfers between two molecules.
In humans, only two coenzyme B-12-dependent enzymes are known:
- MUT which uses the AdoB-12 form and reaction type 1 to catalyze a carbon skeleton rearrangement (the X group is -COSCoA). MUT's reaction converts MMl-CoA to Su-CoA, an important step in the extraction of energy from proteins and fats (for more see MUT's reaction mechanism). This functionality is always lost in vitamin B-12 deficiency, and can be measured clinically as an increased methylmalonic acid (MMA) level. Unfortunately, an elevated MMA, though sensitive to B-12 deficiency, is probably overly sensitive, and not all who have it actually have B-12 deficiency. For example, MMA is elevated in 90-98% of patients with B-12 deficiency; however 25-20% of patients over the age of 70 have elevated levels of MMA, yet 25-33% of them do not have B-12 deficiency. For this reason, MMA is not routinely recommended in the elderly. The "gold standard" test for B-12 deficiency continues to be low blood levels of the vitamin. The MUT function, however, remains the one B-12 function which cannot be restored with folate supplementation, and which is necessary for myelin synthesis (see mechanism below) and certain other functions of the central nervous system. Other functions of B-12 related to DNA, as well as elevated homocysteine levels (see below) can often be corrected with supplementation with the vitamin folic acid.
In a vitamin B12-dependent MUT reaction, methionine is subsequently converted to S-adenosyl-methionine. S-adenosyl-methionine is necessary for methylation of myelin sheath phospholipids. In a second reaction dependent on MUT, B-12 is used to convert methylmalonyl coenzyme A into succinyl coenzyme A. Failure of this second reaction to occur results in elevated levels of methylmalonic acid. Excessive methylmalonic acid will prevent normal fatty acid synthesis, or it will be incorporated into fatty acid itself rather than normal malonic acid. If this abnormal fatty acid subsequently is incorporated into myelin or if the methylation of the myelin sheath phospholipids fails to occur, the resulting myelin will be too fragile, and demyelination will occur. The result is subacute combinded degeneration of central nervous system and spinal cord.
- MTR, a methyl transfer enzyme, which uses the MeB-12 and reaction type 2 to catalyze the conversion of the amino acid Hcy into Met (for more see MTR's reaction mechanism) This functionality is lost in vitamin B-12 deficiency, and can be measured clinically as an increased homocysteine level in vitro. Increased homocysteine can also be caused by a Folic Acid folate deficiency, since B-12 helps to regenerate folate, and thus decrease the need for it in the diet. There is some controversy over whether it is the reduced availability of methionine, or the reduced availability of THF (produced in the conversion of homocysteine to methionine) that is responsible for the reduced availability of 5,10-methylene-THF. In any case, 5,10-methylene-THF is involved in the synthesis of thymine, and hence reduced availability of 5,10-methylene-THF results in problems with DNA synthesis, and ultimately in ineffective production of blood cells, and also in intestinal wall cells which are responsible for absorption, in the once-dreaded and fatal disease, pernicious anemia. All of these effects, including the anemia of pernicious anemia, resolve if sufficient folate is at hand, making this best known function of B-12 (the one involved with DNA synthesis and restoration of cell-division and anemia) actually a facultative function which is mediated by folate.
On the other hand, the absolutely B-12 dependent MUT reaction (mentioned first) is now the one with the most important secondary effects, now that folic acid is being added to fortify flour in many countries (so that folate deficiency is now more rare), and now that folate-sensitive tests for anemia and erythrocyte size are routinely done in even simple medical test clinics (so these biochemical effects are more often directly detected). In the MUT reaction, the transmethylating agent S-adenosylmethionine (SAMe) is produced, which is involved in the synthesis of myelin, necessary for normal nerve function. Methylmalonic acid (MMA), produced when B-12 is deficient and MUT is inactive, is also a myelin destabalizer, as noted. These reasons explain why B-12 deficiency causes neuropathies, even if folic acid is present in good supply and anemia is not present. In addition, SAMe is involved in the manufacture of certain neurotransmitters, catecholamines and in brain metabolism. These neurotransmitters are important for maintaining mood, possibly explaining why depression is associated with B-12 deficiency.
Catabolism
Diseases / Conditions Related to Nutrition
guidelines <p>
- Vitamin B12 Deficiency
- Pernicious Anemia
- Megaloblastic Anemia
- Anemia
- Cervical Cancer
- Adenocarcinoma
- Homozygous sickle cell disease
Associated decreased protein/metabolite profile
Associated increased protein/metabolite profile
Other (Monogenic) Disorders
Nutritional Information
Markers of homeostasis and / or health
| Category | Markers | sign yes/no/? | I/D | S/I | ref | score |
| inflammation, immune response | CRP / hsCRP | Yes
No | D
D | S
I | 4
4 | 2 |
| fibrinogen | Yes
No | D
D | S
I | 4
4 | 2 | |
| Albumin | ||||||
| White blood cell count | No
Yes | ?
I | S
I | 4
4 | 2 | |
| TNF-alpha | ||||||
| Il-6 | ||||||
| Il1-beta | ||||||
| Il-10 | ||||||
| Prostaglandin F2alpha | ||||||
| Prostaglandin E1 (PGE1) | ||||||
| Prostaglandin E2 (PGE2) | ||||||
| Thromboxane B2 | ||||||
| Nitric Oxide (NO) | ||||||
| Serum Amyloid A (SAA) | ||||||
| NfkB | ||||||
| alpha1-antichymotrypsin | ||||||
| oxidative stress | 8(OH)-DG | |||||
| F2-isoprostanes | ||||||
| 8-iso-prostaglandin F2alpha | ||||||
| oxidized LDL | ||||||
| SOD | ||||||
| TBARS | ||||||
| myeloperoxidase | ||||||
| nitrotyrosine | ||||||
| Metabolic stress | diastolic BP | |||||
| systolic BP | ||||||
| total cholesterol | No
No | S
S & I | 5
8 | 2 | ||
| LDL | Yes & No (!)
No No | I
? ? | I
S S & I | 8
8 8 | 2 | |
| HDL | ||||||
| HDL/TC | ||||||
| triglycerides | No | S & I | 8 | 2 | ||
| homocysteine | Yes (!!)
Yes (!!!) Yes Yes No Yes Yes Yes Yes Yes No | D
I I I ? I I I I I ? | S
S S S I S S I S S I | 1
3 7 9 9 13 14 10 15 17 17 | 2
3 3 3 3 3 3 3 3 3 3 | |
| tPA/PAI-1 | ||||||
| Fibrin fragment D-dimer | ||||||
| Factor VIIa | ||||||
| sICAM | No | ? | S & I | 4 | 2 | |
| Monocyte chemotactic protein 1 (MCP1) | ||||||
| fasting glucose | ||||||
| fasting insulin | ||||||
| OGTT | ||||||
| insulin tolerance test | ||||||
| HbA1c | ||||||
| fructosamine |
(!) No in men, yes in women; (!!) marker = MMA; (!!!) marker = vitamin B12 status
Determinants of status
| Category | Determinants of status | sign yes/no/? help | independent of intake yes/no/? |
| general | gender | No (ref 1)
Yes (ref 5) | ?
? |
| age (adults) | Yes (ref 1)
No (ref 2) No (ref 5) No (ref 6) Yes (ref 7) Yes (ref 15) | Yes
? ? ? ? ? | |
| age (children) | Yes (ref 13) | ? | |
| ethnicity | Yes (ref 5) | ? | |
| physiological status | polymorphisms | Yes (ref 18) | ? |
| pregnancy | |||
| lactation | |||
| menopause | |||
| physical fitness | |||
| gut flora | |||
| anthropometric variables | body weight | ||
| BMI | No (ref 11) | ? | |
| waist circumference | |||
| fat free mass | |||
| Lifestyle variables | smoking | Yes (ref 8)
No (ref 12) | ?
? |
| physical activity | No (ref 5) | ? | |
| alcohol use | |||
| medication use (incl. contraceptive pill) | |||
| stress |
References
- Bates, CJ, Schneede J, Mishra G, Prentice A, Mansoor MA. Relationshio between methylmalonic acid, homocysteine, vitamin B12 intake and status and socio-economic indices, in a subset of participants in the Britisch National Diet and Nutrition Survey of people aged 65 y and over. Eur J Clin Nutr 2003; 57: 349-357.
- Ducros V et al.. Zinc supplementation does not alter plasma homocysteine, vitamin B12 and red blood cell folate concentrations in French elderly subjects. J of Trace Elements in Medicine and Biology. 2008, doi :10.1016/j.jtemb.2008.08.003.
- Fakhrzadeh H et al.. Total plasma homocysteine, folate, and vitamin B12 status in healthy Iranian adults : the Tehran homocysteine survey (2003/2004) / a cross-sectional population based study. BMC Public Health 2006 ; 6 : 29.
- Folsom AR, Desvarieux M, Nieto FJ, Boland LL, Ballantyne CM, Chambless LE. B vitamin status and inflammatory markers. Atherosclerosis 2003;169:169-74.
- Ford ES, Giles WH. Serum vitamins, carotenoids, and angina pectoris: findings from the National Health and Nutrition Examination Survey III. Ann Epidemiol 2000;10:106-16.
- Forster S and Gariballa A. Age as a determinant of nutritional status: a cross sectional study. Nutriotnal Journal 2005; 4: 28.
- Ganji V, Kafai MR. Demographic, health, lifestyle, and blood vitamin determinants of serum total homocysteine concentrations in the third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr 2003;77:826-33.
- Hooper PL et al.. Vitamins, lipids and lipoproteins in a healthy elderly population. Internat J of Vit Nutr Res 1983; 53: 412-419.
- Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH, Selhub J. Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr 2001;73:613-21.
- Klerk M, Verhoef P, Verbruggen B et al. Effect of homocysteine reduction by B-vitamin supplementation on markers of clotting activation. Thromb Haemost 2002;88:230-5.
- McNeill G, Vyvyan J, Peace H et al. Predictors of micronutrient status in men and women over 75 years old living in the community. Br J Nutr 2002;88:555-61.
- Northrop-Clewes CA, Thurnham DI. Monitoring micronutrients in cigarette smokers. Clin Chim Acta 2007;377:14-38.
- Papandreou D et al.. Total serum homocysteine, folate and vitamin B12 in a Greek school age population. Clinical Nutrition 2006; 25: 797-802.
- Refsum H, Nurk E, Smith AD et al. The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease. J Nutr 2006;136:1731S-40S.
- Refsum H et al.. Holotranscobalamin and total transcobalamin in human plasma: determination, determinants and reference values in healthy adults. Clinical Chemistry 2006; 52: 129-137.
- Requejo AM et al.. Folate and vitamin B12 status in a group of preschool children. Int J Vit Nutr Res 1997; 67 (3): 171-175.
- Selhub J, Jacques PF, Bostom AG, Wilson PW, Rosenberg IH. Relationship between plasma homocysteine and vitamin status in the Framingham study population. Impact of folic acid fortification. Public Health Rev 2000;28:117-45.
- Verkleij-Hagoort AC, van Driel LM, Lindemans J et al. Genetic and lifestyle factors related to the periconception vitamin B12 status and congenital heart defects: a Dutch case-control study. Mol Genet Metab 2008;94:112-9.