Vitamin cobalt deficiency

Cobalt is one of twenty-seven known elements essential to humans (28) (see Mineral NUTRIENTS). It is an integral part of the cyanocobalamin [68-19-9] molecule, ie, vitamin B 2> only documented biochemically active cobalt component in humans (29,30) (see Vitamins, VITAMIN Vitamin B 2 is not synthesized by animals or higher plants, rather the primary source is bacterial flora in the digestive system of sheep and cattle (8). Except for humans, nonmminants do not appear to requite cobalt. Humans have between 2 and 5 mg of vitamin B22, and deficiency results in the development of pernicious anemia. The wasting disease in sheep and cattle is known as bush sickness in New Zealand, salt sickness in Florida, pine sickness in Scotland, and coast disease in AustraUa. These are essentially the same symptomatically, and are caused by cobalt deficiency. Symptoms include initial lack of appetite followed by scaliness of skin, lack of coordination, loss of flesh, pale mucous membranes, and retarded growth. The total laboratory synthesis of vitamin B 2 was completed in 65—70 steps over a period of eleven years (31). The complex stmcture was reported by Dorothy Crowfoot-Hodgkin in 1961 (32) for which she was awarded a Nobel prize in 1964. 

Co deficit Everywhere Low content of Co in Podsoluvisols, Podzols, Arenosols and Histosols. The average Co content in plant species is < 5 ppb The decrease of Co content in tissues decrease of vitamin BJ2 in liver (tr.—130 ppm), in tissue (tr.—0.05 ppm), in milk (tr.—3 ppm). Synthesis of vitamin Bi2 and protein is weakened. Cobalt-deficiency and Bj2 vitamin-deficiency. The number of animal diseases is decreasing in raw sheep —cattle — pigs and horses. Low meat and wool productivity and reproduction... 

Cu + Co deficit Especially in Swamp ecosystems Low content of Cu and Co in Podsoluvisols, Podzols, Arenosols and Histosols. Declining contents of Cu and Co in forage species (Cu from 3 to 0.7 ppm, Co < 5 ppb) Depressed synthesis of BJ2 vitamin and oxidation ferments. Cobalt-deficiency and B12 vitamin-deficiency complicated by Cu deficiency. The prevalent diseases of sheep and cattle... 

I, Co, Cu deficit Various mountain regions Carpathian, Caucasian, Crimea, Tien-Shan, etc Mountain soils Endemic increase of thyroid gland and endemic goiter, Cobalt-deficiency and B12 vitamin-deficiency... 

The need to include a variety of minerals in experimental diets has already been mentioned this was especially stressed (1920-1930) by Boyd-Orr, the director of the Rowett Institute for Animal Nutrition in Scotland. Increasingly refined food sources led to the identification of large numbers of trace elements (e.g., Cu, Mn, Mo, Zn) whose importance in the diet was suggested from hydroponic experiments with plant seedlings. Cobalt is an example of such a trace element. Vitamin Bj2 is synthesized by bacteria in the rumens of sheep and cattle but is absent from their fodder. In Australia, sheep feeding on cobalt-deficient pastures failed to thrive because vitamin B12 could no longer be made. 

Vitamin B12 is a very complex molecule that contains an atom of cobalt. Pernicious anemia is a vitamin B12 deficiency disease. Vitamin B12 is a... 

The human body contains only about 1.5 mg of cobalt, almost all of it is in the form of cobalamin, vitamin B12. Ruminant animals, such as cattle and sheep, have a relatively high nutritional need for cobalt and in regions with a low soil cobalt content, such as Australia, cobalt deficiency in these animals is a serious problem. This need for cobalt largely reflects the high requirement of the microorganisms of the rumen (paunch) for vitamin B12. All bacteria require vitamin B12 but not all are able to synthesize it. For example, E. coli lacks one enzyme in the biosynthetic... 

Cohall is present in vitamin Bi to Ihe extent of about 4ci-. Lack of cobalt in tlie soil and feedstuffs prevents tuniinants from synthesizing all of the vilamin B j for their needs. Thus, cobalt can be added to feedstuffs as the chloride, sulfate, oxide, nr carbonate. Excessive cobalt intakes are toxic, causing a reduction in feed intake and body weight, accompanied by emaciation, anemia, debility, and elevated levels of cobull in the liver. It is of interest to note that clinical coball tnxiciiy closely resembles clinical cobalt deficiency. 

Factors which tend to decrease the availability of this vitamin include (1) cooking losses, since the vitamin is heat labile (2) cobalt deficiency in ruminants (3) intestinal malabsorption or parasites (4) lack of intrinsic factor (5) intestinal disease (6) aging (7) vegetarian diet (8) excretion... 

Cobalt 1-5 mg 3 iig Vitamin Bl2 Part of Vitamin B12, erythropoiesis Vitamin BJ2 deficiency only, because of diet or failure to absorb Unknown... 

Van Vleet JF, Boon GD, Ferrans VJ. 1981. Induction of lesions of selenium-vitamin E deficiency in ducklings fed silver, copper, cobalt, tellurium, cadmium, or zinc Protection by selenium. Am J Vet Res 42 1206-1217. 

Ruminant animals obtain their B12 from bacterial synthesis that takes place in the rumen. As a result, these animals may suffer from vitamin B12 deficiency when they are grazed on cobalt-deficient pastures because the rumen bacteria will be unable to produce the vitamin. 

Answer One of the enzymes necessary for the conversion of propionate to oxaloacetate is methylmalonyl-CoA mutase (see Fig. 17-11). This enzyme requires as an essential cofactor the cobalt-containing coenzyme B12, which is synthesized from vitamin B12. A cobalt deficiency in animals would result in coenzyme B12 deficiency. 

Essential for the formation of vitamin B12 and synthesis of red blood cells. Without it pernicious anaemia follows. Not found in vegetables but it is present in milk, eggs, cheese, meat and liver. Vegetarians must be aware of their possible cobalt deficiency and remedy this... 

Vtamin A supplementation, 564-565 Vitamin B(, 493, 541-542 aminotranK/ei ase, 209 assessmenl of status, 546-550 biochcinistry, 542-545 cardiovascular disease and, 553 homocysteine and, 550-554 homocysbnuria, 550,554 toxidty, 550 water solubility, 27 Vitamin Bs deficiency, 545-546 Vitamin supplements, 551 Vitamin Bu, 493,507, 516 absorption, 81-82 assessment of status, 522-524 biocbemistry, 516-517 chemical structure, 517 Cobalt and, 4t homocystBine and, 553 Vitamin Bij dehdency, 517-524 causes of, 518-522 elderly population, 521,553 folate deficiency and, 507, 511-312, 518 hematologic signs, 513... 

One of the biochemical adverse effects of nitric oxide is inactivation of vitamin B12, with subsequent potentiation of folate deficiency (19). This effect is mediated by irreversible oxidation of the cobalt residue in vitamin B12 to its Co++ and Co forms. This leads to a reduction in methionine synthetase activity, with downstream effects on DNA synthesis. Previous studies have identified five patients with unsuspected vitamin B12 deficiency who developed subacute combined degeneration of the spinal cord following inhalation anesthesia with nitrous oxide... 

Cobalt is found in vitamin Bn, its only apparent biological site. The vitamin is a cyano complex, but a methyl or methylene group replaces CN in native enzymes. Vitamin-Bi2 deficiency causes the severe disease of pernicious anemia in humans, which indicates the critical role of cobalt. The most common type of reaction in which cobalamin enzymes participate results in the reciprocal exchange of hydrogen atoms if they are on adjacent carbon atoms, yet not with hydrogen in solvent water ... 

Lon anemia (Fe deficiency) in humans is common, but is due to low availability to plants rather than low amounts in the soil. Molybdenum deficiency, which prevents microbial nitrogen fixation, and cobalt deficiency in Australian sheep that prevents rumen bacteria from synthesizing vitamin B12, have been reported in Australia. Phosphate deficiency that led to weak bones in grazing animals was reported in Norway. 

Ruminants require cobalt for the bacterial biosynthesis of vitamin B12 in the first stomach. Cobalt-deficient sheep or cattle show diminished feed intakes and weight loss. In cows, milk production declines and the fre-... 

When ruminants are confined to cobalt-deficient pastures it may be several months before any manifestations of pine occur because of body reserves of vitamin... 

Figure 5.3. Growth of vitamin Bn-depleted and vitamin Bn-deficient cells ofP. shermanii in different redox environments. A wild-type cells deprived of cobalt (residual vitamin B about 10 pg/g) were grown in the absence of cobalt (1), under argon gas (2) or in the presence of C0CI2 6H2O at 3 mg/1 (3). In 3, the fmal level of vitamin B12 was 1500 pg/g. B vitamin Bi2-deficient mutant cells were grown in the absence of cobalt (1), but in the presence of 0.03% each of the following reduced glutathione (2), sodium thiosulfate (3), cysteine (4), methionine (5) or tryptone (6). From Iordan et al. (1984).

Vitamin Bn-deficient cells contained about 30-45% less DNA than cells with physiological levels of the vitamin (Vorobjeva and Iordan, 1976 Iordan, 1992). The DNA content in these cells increased by up to 80% when AdoCbl was added to cultures growing in cobalt-ffee medium (Iordan et al., 1983) (Table 5.1). Strains with a potential capacity for high corrinoid synthesis demonstrated a more significant stimulation by exogenous AdoCbl than strains with low synthetic capacity (Fig. 5.7). However, P. acnes represented an exception to this rule it responded weakly to the addition of AdoCbl, despite having a high potential for vitamin Bn synthesis. 

Other natural habitats of propionic acid bacteria are represented by cheese and silage. If one recalls that there are at least 10 bacterial cells in 1 g of cheese, then it becomes clear that bacteria lead a cobalamin-deficient existence. The same is true of bacteria that live in silage, where the cobalamin content is about 0.1 to 2.0 xg per 100 g (Smith and Marston, 1970). In the rumen of ruminants, where cobalt is limited, the cobalamin content is in the range of 0.14-0.41 ng/ml (Dryden et al., 1962). It is clear that these bacteria live at a very low cobalamin level. Therefore, the conclusion is obvious—most propionic acid bacteria lead a vitamin B -deficient mode of life in nature, although they can readily attain high levels of corrinoids under favorable conditions. 

Analysis of the results concerning the DNA synthesis in vitamin Bn-deficient cells allowed us to conclude that a vitamin Bn-independent system may operate in these cells. This system has been investigated in a series of studies (Iordan et al., 1986 Iordan, 1992 Iordan and Petukhova, 1995). After a number of passages in a medium carefully depleted of cobalt (which simulated natural habitats) the cells of P. shermanii contained less than 2 iig of cobalamins per g biomass. These cells, adapted to the vitamin B -free medium, are referred to as vitamin B -depleted cells. The synthesis and activities of ribonucleotide reductase (RNR) were compared in vitamin B -replete (Bi2 ), Bu-deficient and Bn-depleted cells. 

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