Cobalamina – Wikipedia

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Vitamin b twelfth , O Cobalamina , is a red, crystalline, hygroscopic, photosensitive and highly soluble in water substance. It was isolated and characterized following a series of research on pernicious anemia. In 1926 it was discovered that in the liver there is a factor capable of taking care of this pathology and it was isolated and crystallized in 1948. The structure of vitamin B twelfth It was clarified in 1956.

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It is made up of an electric ring (consisting of 4 pyrrolic rings and three metinic bridges) with a cobalt atom coordinated by four nitrogen atoms. Cobalt also presents two perpendicular coordination links compared to the ring plan. The first of them settles with a molecule of 5.6 dimetylbenzimidazole linked, in turn, to a 3-phosphate rebuk. The second link is established with different functional groups (-r) which can be:

The metabolically active forms are the Metil- and the 5′-deossiadenosilcobalamine. Cianocobalamin is an artifact that is formed during the extraction processes as Papain is used, protease that is activated by the addition of CN-. Hydroxicobalamin is the natural form with which vitamin is usually taken.

In the stomach, the acidic environment and pepsin detach cobalamine from the proteins to which it is associated, and then bind to the cobalophillin (also called salivic polypeptide r binder or apocorrine), a burgopruen secreted in saliva. Later, in the duodenum, the action of the proteases produced by the pancreas determines the separation between cobalophillin and cobalamin, this favored by an alkaline environment. Finally, cobalamine is linked to the intrinsic factor, a glycoprotein issued by the parietal cells of the stomach, with the mediation of a falling receptor and a pH of about 6.5.

The intrinsic vitamin-facators complex is recognized by a specific receptor (megaline-cubiline complex) located on the Aleo entities, which binds them and through a process of endocytosis allows their transport inside the cell. The vesicle thus trained reaches the opposite part of the enterocity and, merging with the Basulations membrane, free everything outside. During this process, cobalaminism detaches itself from the intrinsic factor (perhaps by the action of the lysosomial vesicles) and once outside it is linked by two transport proteins that bring vitamin to the tissues: the transcobalamin I and the transcobalamin II. The complex that is formed with these proteins is recognized by a specific receptor that allows the entry of vitamin into the cells, once again for endocytosis.

The cobalt atom (an otherwise extremely toxic element for the organism) in hydroxicobalamin is in the state of oxidation +3. To obtain the active form, a Flavoprotein Reductase intervenes, using Nadh, which reduces the cobalt first to +2 and then to +1. Under this state of oxidation, cobalt can be linked to the C5 of an ATP molecule, displacing the three phosphate groups, and give rise to the 5-deossiadenosilcobalaminine.

In the form of deoxiadenosilcobalamine, vitamin B twelfth intervenes in two processes:

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In the form of methylcobalamine intervenes in this reaction:

Interestingly, this reaction is one of the few in which vitamin B contact come in contact twelfth and folic acid. If this reaction does not take place, the transformation of methyltetrahydrofolato into tetrahydrofolato, with consequent accumulation of the first compound is blocked. The decrease in tetrahydrofolato and its derivative methylentetrahydrofulated determines a block of enzymes that need these two compounds. This involves a dysfunction of the Metabolic Streets producing purines and single -nophosphate dexossitimidine.

Since the reactions affected by the 5-deossiadenosilcobalaminine intervene in the metabolism of fatty acids it is believed that their blocking can mainly affect the neuronal membranes and this would explain the very frequent neurological involvement in case of vitamin B deficiency twelfth [2] .

Differential diagnosis : megaloblastic anemia induced by the deficiency of vitamin B12 can also be caused by a deficit of folic acid. The triggering cause must be ascertained the megaloblastic anemia to avoid the risk of a progression/irreversibility of the neurological symptoms associated with the deficiency of vitamin B12, but not of folic acid (the administration of 0.1 mg/day of folic acid induces remission of symptoms of anemia in patients with vitamin B12 deficit and, vice versa, 10 µg/day of vitamin B12 in patients with folic acid deficit). In some cases, supplementation with high doses of folic acid instead of improving the clinical symptoms of anemia has caused their worsening [3] : in foods and supplements the dose of folic acid should not exceed the amount of 1 000 µg/day [4] . Other possible causes of macrocytosis (larger red blood cells than normal, which are also found as a characterizing element in megaloblastic anemia) include alcoholism, cirrhosis of liver, hypothyroidism, myelodysplastic syndromes, aplastic anemia, iatrogenic (antiviral and antineoplastic cytotoxic drugs), pregnancy.

Monitoring levels of vitamin B12 : check the serum levels of vitamin B12 after a month from the start of the treatment and in case of each variation, therefore at intervals of 3-6 months. Vitamin B12 levels lower than 200 pg/ml are considered indicative of a vitamin deficit. High levels of homocysteine ​​and methylmalonic acid can also be indicative of hypovitaminosis from vitamin B12. Homocistein increases in case of low levels of vitamin B12 (> 13 µmol/l), but since it also suffers from other factors (vitamin B6 and folic acid) is an unprotected marker. Metilmalonic acid is a more specific marker because its conversion to acetylcoa depends directly on vitamin B12: in the event of a shortage of vitamin the serum levels of methylmalonic acid increase (> 0.4 µmol/l) [5] . However, if the high levels of methylmalonic acid are still accompanied by high levels of malonic acid, this can also indicate the often neglected metabolic disease [6] of the combined Malonica and methylmalonica aciduria (cmamma) [7] .

Oral contraceptives : Patients who use oral contraceptives may show a lowering of plasma levels of vitamin B12 (278 vs. 429 pg/ml respectively women who use or do not use oral contraceptives) [8] . In healthy women, however, the use of oral contraceptives does not make the supplementation of vitamin B12 necessary [9] .

Malarattia tiroid autoimmune (AITD) : patients with autoimmune thyroiditis have an increased risk of developing pernicious anemia (anemia caused by reduced absorption of vitamin B12) compared to the population in general. In a clinical study, the prevalence of pernicious anemia, in patients with low levels of vitamin B12 (≤133 prosecutor/l) and high levels of gastrine, was 31% [ten] .

Gastric anomalies associated with pernicious anemia : In patients with pernicious anemia, increased gastrin levels (16.5% of cases), reduction in pepsinogen I (22% of cases), acloridia (29% of cases) and presence of antibodies to gastric parietal cells may occur. (23% of cases) [11] . Gastrin levels are often high (> 1,000 pg/ml) for non -control by the hydrochloric acid, whose production in the stomach is reduced/absent for gastric atrophy.

Vegan diet : The people who follow vegan diets with complete abolition of meat, fish, eggs and milk must take supplements containing vitamin B12 or added foods (cereals enriched with vitamin B12) to avoid developing hypovitaminosis. Children breastfed by women who follow a vegan diet are particularly at risk of going to the lack of vitamin B12 within a few months of birth with severe consequences on physical and neurological development [twelfth] [13] [14] .

Energy supplements : supplementation with vitamin B12 was not strengthened the physical performance in subjects with adequate dietary intake of vitamin [15] .

Animal foods contain this vitamin in adequate quantities. In particular, the foods that contain the most are liver, molluscs and some types of fish. For this reason, for those who choose a completely vegan diet, the use of vitamin B supplements is strongly advisable to twelfth , or take products such as soy milk, burger and vegetable yogurt (in some of these products it is written on the package if they contain the B twelfth ).
In nature the synthesis of vitamin B twelfth It takes place only by microorganisms (some archeers and bacteria) [16] [17] [18] . The cyanobacteria improperly called blue algae (Spirulina, Klamath) instead produce inactive analogues (pseudo B twelfth ) [19] , while certain algae acquire vitamin B twelfth from the symbiotic relationship with bacteria [20] .
In the human intestine there are cobalamic synthesizing bacteria. These bacteria are located in areas where the intrinsic factor does not come, so the absorption of the latter is negligible, albeit not zero [21] .

A deficiency of vitamin B twelfth The parietal cells of the stomach or by resection of the parts of this organ that secrete intrinsic factor (cardiacs and fund) are mostly occurred following interesting pathological processes.

Cobalamin deficit can also take place due to chronic pathologies against the intestine, such as Crohn’s disease, and causes the appearance of pernicious anemia, a disease characterized by: megaloblastic anemia and nervous system disorders. In these cases, it is always important to evaluate the concentration of cobalamin and folic acid as the lack of the latter also causes a picture of megaloblastic anemia, however without nervous interest. The addition of folic acid in a pernicious anemia situation improves the anemic framework but has no effect on the disturbances of the nervous system which, on the contrary, continue to worsen.

It has been seen that the intake of high quantities of vitamin C (> 1 g) can, over time, generate carenial states of cobalamin. This occurs in that, in high doses, vitamin C, in the presence of iron, can be oxidant and form free radicals that damage cobalamina and the intrinsic factor.

In case of high doses of vitamin B twelfth (in the form of cyanocobalamin) the excess quantity is eliminated with the urine, without causing toxic accumulation effects [22] [23] . Although it was believed that the assumption of quantities greater than 200 µg could present toxicity risks [24] , in clinical trials the administration of 400 µg for 40 months and 1 000 µg for 5 years has not been associated with adverse effects [23] .

  1. ^ Sigma Aldrich; rev. of 03.12.2012, referred to Cianocobalamine
  2. ^ Vitamin B12 (cobalamin) da Pharmamedix . are pharmamedix.com . URL consulted on December 21, 2014 .
  3. ^ Johnson M.A., Nutr. Rev., 2007, 65, 451
  4. ^ Institute of Medicine, Food and Nutrition Board – Dietary Reference Intake, 1998, Washington DC, National Academy Press
  5. ^ Klee G.G., Clin. Chem., 2000, 46, 1277
  6. ^ ( IN ) NIH Intramural Sequencing Center Group, Jennifer L Sloan e Jennifer J Johnston, Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria , in Nature Genetics , vol. 43, n. 9, 2011-09, pp. 883–886, DOI: 10.1038/NG.908 .
  7. ^ Monique G. M. de Sain-van der Velden, Maria van der Ham e Judith J. Jans, A New Approach for Fast Metabolic Diagnostics in CMAMMA , vol. 30, Springer Berlin Heidelberg, 2016, pp. 15–22, DOI: 10,1007/8904_2016_531 , ISBN 978-3-662-53680-3.
  8. ^ Lussana F. et al., Thromb. Res., 2003, 112 (1-2), 37
  9. ^ Mooij P.N. et al., Contraception 1991, 44 (3), 277
  10. ^ Ness-Abramof R. et al., Am. J. Med. Sci., 2006, 332 (3), 119
  11. ^ Juncà J. et al., EUR. J. Haematol., 2006, 77 (6), 518
  12. ^ Kaiser L., Allen L.H., J. Am. Diet. Assoc., 2008, 108, 553
  13. ^ Von Schenck U. et al., Arch. Dis. Childhood, 1997, 77, 137
  14. ^ Filmato audio The dark side of the vegan diet . are YouTube . URL consulted on October 15, 2017 .
  15. ^ Lukaski H.C., Nutrition, 2004, 20, 632
  16. ^ ( IN ) Ely, Raux, H. L. Schuber and M. J. Wore. Biosynthesis of cobalamin (vitamin B twelfth ): a bacterial conundrum . Cellular and Molecular Life Sciences , Volume 57, Numbers 13-14 (2000): Pages 1880-1893; DOI: 10.1007/PL00000670.
  17. ^ ( IN ) Marjorie A. Darken. Production of vitamin B twelfth by microorganisms and its occurrence in plant tissues . The Botanical Review , Volume 19, Number 2 (1953): Pages 99-130; DOI: 10.1007/BF02861845.
  18. ^ ( IN ) J.-h. Marcens, H. Barg, M.J. Wars, D. Jahn. Microbial production of vitamin B twelfth . Applied Microbiology and Biotechnology , 2002; Volume 58: Pages 275–285; DOI: 10.1007/s00253-001-0902-7
  19. ^ ( IN ) Stephen Walsh. Algae and B twelfth Filed l’11 maggio 2012 in Internet Archive.. Published online: 7 June 2002. ( IT ) Translation The Caring Di Luciana Baroni.
  20. ^ ( IN ) Martin T. Croft, Andrew D. Lawrence, Evelyne Raux-Deery, Martin J. Warren & Alison G. Smith. Algae acquire vitamin B twelfth through a symbiotic relationship with bacteria . Nature , 3 November 2005; Volume 438: Pages 90-93; DOI: 10.1038/nature04056; Received 18 May 2005; Accepted 15 July 2005.
  21. ^ B12 in Plant Foods . are veganhealth.org . URL consulted on 23 December 2016 (archived by URL Original November 3, 2008) .
  22. ^ ( IN ) Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline . Washington, DC: National Academy Press, 1998. (cit. in: National Institutes of Health. Dietary Supplement Fact Sheet: Vitamin B twelfth .)
  23. ^ a b ( IN ) Philip R. Liebson. Women’s Health Initiative (WHI) Dietary Trial and Norwegian Vitamin Trial (NORVIT) . Preventive Cardiology , Summer 2006; Volume 9, Issue 3: Pages 178–182. (cit. in: ( IT ) Innova et Bella, Vitamina B twelfth (Cobalamina). Toxicity . are pharmamedix.com . URL consulted on April 29, 2012 . )
  24. ^ Italian society of human nutrition, Larn. Hydrosoluble vitamins. Vitamin B12 . are sinu.it . URL consulted on April 29, 2012 (archived by URL Original January 12, 2012) .
  • Aldo Mariani Costantini, Carlo Cannella, Giovanni Tomassi. Fundamentals of human nutrition . The scientific thought publisher.

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