Cobalt

I.  Physiological Role

1. Component of vitamin B₁₂
   1. Co occupies a unique position among the trace elements. It is an integral part of a vitamin for animals which are dependent upon the symbiotic activities of their Gl microorganisms for their supply of the vitamin.
2. Vitamin B₁₂ dependent enzymes:
   1. MethylmalonyI-CoA mutase
      1. Propionyl CoA  ®  Methylmalonyl Co-A  ®  Succinyl Co A
         Propionic acid, the primary gluconeogenic substrate in fed ruminants, is metabolized solely by the methylmalonate pathyway in the liver
   2. Methyltetrahydrofolate homocysteine methyltransferase
      1. (Following from J. Anim. Sci. 65:1702, 1987) (see FASEB J. 4:1450, 1990):
         1. Catalyzes the transfer of a methyl group from N⁵-methyltetrahydrofolate to homocysteine, producing tetrahydrofolate and methionine
         2. Indirect relationship of reduced activity of 5-methyltetrahydrofolate homocysteine methyltransferase during Co deficiency to increased urinary formiminoglutamate output
         3. Steps inhibited by deficiency are indicated by open arrows:
         4. Vitamin B₁₂'s methyl group transfer activity is essential for a normal functioning nervous system
3. Vitamin B₁₂ is necessary for normal hemopoiesis by facilitating the cyclic metabolism of folic acid which is essential for thymidine and thus DNA synthesis

II.  Tissue Distribution

1. Co is widely distributed throughout the body but concentrations are generally higher in kidney, liver and bone than in other tissues
2. Liver should contain at least 0.3 ppm vitamin B₁₂ in fresh tissue to be considered adequate
3. Liver Co concentration is an unreliable criterion of vitamin B₁₂ status of ruminants
   1. Liver Co concentration can be increased by massive doses without increasing B₁₂ synthesis
   2. Ruminants fed Co-deficient diets can be maintained in health by vitamin B₁₂ injections
4. (From Am. J. Clin. Nutr. 18:176-184, 1966)
   1. Ewes were fed a Co deficient diet for 2 weeks then dosed daily with ⁶⁰COCl₂ for 5 days
   2. They were slaughtered 3 wk after cessation of feeding 60Co when urinary 1 Co was negligible
   3. Approximately 95% of the total 6-Co in liver was associated with cyanocobalamin (vitamin B₁₂)
      1. Ionic ⁶⁰Co content was only 2.5 - 3.6% of total 60Co in liver and 6.4 - 7.9% in muscle
      2. This was part of an investigation in which sheep were used to      synthesize ⁶⁰Co-labeled vitamin B₁₂ for use in other research

III.  Absorption and Excretion of Co

1. Although amounts and sites of Co absorption have been determined, absorption of vitamin B₁₂ rather than Co should be considered
   1. Nonruminants have a dietary requirement for B₁₂ but no Co
   2. Ruminants have a dietary requirement for Co, but their metabolic requirement is for B₁₂ rather than Co
      1. Co functions primarilyy as a component of B₁₂
      2. B₁₂ is produced by rumen microorganisms rather than in tissues of the host animals
      3. Co need not be absorbed as such since B12 is produced in the rumen

IV.  Interactions with Other Nutritional Factors

1. Silicofluoride in water can inhibit rumen organisms which synthesize B₁₂. This can condition a Co (vitamin B12 deficiency in cattle
2. Co infused with other salts or organic compounds:
   1. Reduces absorption of Na, K, P, glucose, glycine and water
   2. Elevates absorption of Ca
   3. Increases secretion of Na into the intestinal lumen.
3. High dietary Mo (200 ppm) reduces ruminal synthesis of B₁₂
4. Excess Co reduces Fe absorption, but utilization of Cu and Fe in
   Co deficient ruminants can be improved by supplemental Co. (Co appears to share with Fe at least part of the same intestinal mucosal transport system.) Fe deficiency and other conditions which increase Fe absorption also increase Co absorption (Am. J. Dig. Dis. 21:305, 1976)
5. Injected B12 or oral Co will help prevent Cu deficiency in cattle even though Co does not appear to modify the reduced liver Cu when Mo is excessive
6. Ruminants receiving adequate Co are less susceptible to Se toxicosis (B₁₂
   functions in formation of dimethyl selenide and other excretory products of Se)

V.  Dietary Requirements for Co

1. Nonruminants have no known dietary requirement for Co by itself but require dietary B₁₂
   1. Supplemental vitamin B₁₂
   2. Products of animal origin - meat, milk, eggs for humans
   3. Vegetables, fruits and grains contain B₁₂ only if contaminated by animal feces
   4. Nonruminants may get some benefit from microbial synthesis of B₁₂ if allowed access to feces
2. Ruminants require dietary Co (0.1 ppm in DM)
   1. Microorganisms in the rumen synthesize vitamin B12 from Co (Rumen contents may contain 10 mg B₁₂/g DM)
   2. B12 is much less effective when given orally than when given parenterally to ruminants
      1. Absorption of B₁₂ by ruminants is low (<3%)
      2. Total B₁₂ activity in rumen contents may be 10-20 x greater than true B₁₂ activity
      3. Rumen microorganisms may convert dietary or rumen B₁₂ to Co- containing B12-1ike molecules with no physiological function for the host

VI.  Source of Co for ruminants

1. Natural feeds except in Co deficient areas
2. Co in trace mineralized salt. Co oxide, Co carbonate an dco sulfate are effective for ruminants
3. Fertilization of pasture with about 140 g Co sulfate per acre will usually last up to 3 years
   1. Extractable Co in soil has predictive value for vitamin B₁₂ status of lambs born to ewes receiving home grown feed (TEMA 6, p 473, 1988)
4. Spraying of plant foliage
5. Slow release Co bullets in reticulum (see TEMA 6, pages 639 & 669, 1988)

VII.  Co Deficiency

1. Nonruminants
   1. Co deficiency has not been seen in nonruminants
   2. Horses thrive on pastures where cattle or sheep could not survive
   3. Pernicious anemia results from impaired absorption of B₁₂ due to a lack of Castle's intrinsic factor in the stomach lining
      1. a.            Intrinsic factor is found in stomach lining
      2. b.            Pernicious anemia patients have been treated with scrapings from pig stomach lining
2. Ruminants
   1. Withdrawal of Co from diet results in a marked drop in B₁₂ activity in rumen contents
      1. No obvious impairment of physiological function until liver B₁₂ falls below 0.15 ppm (normal liver B₁₂ is 0.2-0.3 ppm)
      2. First clinical symptoms of Co deficiency appear when blood B₁₂ falls from normal range, of 1-3 m/l to 0.3 mg/l or less)
   2. Clinical symptoms of deficiency
      1. Listlessness
      2. Gradual, then rapid loss of appetite and weight
      3. Reduced milk production
      4. Rough hair coat; wool with Iow breaking strength
      5. Anemia resulting in pale skin and mucous membranes
      6. Emaciation, muscle incoordination, stumbling gait, death
   3. Biochemical changes
      1. Depletion of vitamin B₁₂ stores in liver and kidney
      2. Low plasma glucose and alkaline phosphatase
      3. Fatty degeneration of the liver
      4. Hemosiderosis of the spleen
      5. Low hematocrit and hemoglobin levels
         1. Erythropoiesis can be restored by folic acid treatment, which has no effect otherwise, suggesting the anemia is secondary
      6. Urinary output of methylmalonic acid increases 5-12 times
         1. B₁₂ is an essential cnmp~nent of methylmalonyl CoA mutase
         2. Ruminants are dependent on gluconeogenesis from propionate
         3. Urinary loss of its primary metabolite, methylamalmic acid, can have serious physiological consequences
         4. Livers of Co deficient animals can metabolize malate and succinate normally but cannot convert propionate to succinate
      7. Urinary output of formino glutamic acid may be elevated 30X

VIII.  Excess Co

1. Dietary Co levels considered excessive:
   1. >20 ppm for cattle and >50 ppm for sheep
   2. Toxic levels appear to be at least 200 times the requirement for ruminants so toxicosis is less likely than deficiency
   3. Co toxicity may occur accidently when Co is used in salt licks, in mixed rations, or applied to pastures
2. Toxic signs in ruminants
   1. Fatty infiltration of liver
   2. Slight pulmonary edema
   3. Congestion
   4. Anorexia and decreased gain
   5. Petechial to ecchymotic hemorrhages in small intestine
3. >200 ppm is considered excessive for swine
   1. Above 400 ppm, anorexia, decreased gain, stiff legs, humped back, incoordination, muscular tremors
4. > 5 ppm for chickens is considered excessive
   1. No adverse effects at 4.7 ppm
   2. At 50 ppm dietary Co, emaciation, debility, inanition, death
5. Signs of Co toxicity in nonruminants
   1. Polycythemia (in addition to symptoms listed above)

COBALT REFERENCES

• Croom, W.J., Jr., A. H. Rakes, A. C. Linnerud, G. A. Duchorme, and J. M. Elliot. 1981. Vitamin B12 administration for milk fat synthesis in lactating dairy cows fed a low fiber diet. J. Dairy Sci. 64:1555-1560
• Daugherty, M.S., M.L. Galyean, D.M. Hallford, and J.H. Hagemann. 1986. Vitamin B₁₂ and monensin effects on performance, liver and serum vitamin B12 concentrations and activity of propionate metabolizing hepatic enzymes in feedlot lambs. J. Anim. Sci. 62:452
• Frobish, R.A., and C.L. Davis. 1977. Theory involving propionate and vitamin B12 in the low-fat syndrome. J. Dairy Sci. 60:268
• Heyssel, R.M., R.C. Bozian, W.J. Darby, and M.C. Bell. 1966. Vitamin B12 turnover in man. The assimulation of vitamin B12 from natural foodstuff by man and estimates of minimal daily dietary requirements. Am. J. Clin. Nutr. 18:176-184
• Mills, C.F. 1987. Biochemical and physiological indicators of mineral status in animals: copper, cobalt and zinc. J. Anim. Sci. 65:1702-1711
• Peters, J.P. and J.M. Elliot. 1983. Effect of vitamin B12 status on performance of the lactating ewe and gluconeogenesis from propionate. J. Dairy Sci. 66:1917-1925
• Stebbins, R.S., and G. Lewis. 1983. Urinary forminoglutamic acid in lambs. Vet Rec. 112:328. TEMA 6, 1988. pages 397, 473, 535, 639, 669
• Quirk, M.F. and B.W. Norton. 1982. The effects of cobalt supplementation on pregnant heifers on lactation and calf growth. Proc. Aust. Soc. Anita. Prod. 14:293-296

Cobalt — Co (atomic number 27)

Humans need cobalt almost only as the center atom of vitamin B12. Loose cobalt salts are not a substitute for B12.

Vitamins, Major Elements, Trace Elements, Toxic Elements

Vitamins

Vitamin A	Vitamin B1 (Thiamin)	Vitamin B2 (Riboflavin)	Vitamin B3 (Niacin)
Vitamin B5 (Pantothenic Acid)	Vitamin B6	Vitamin B12	Vitamin C
Vitamin D	Vitamin E	Vitamin K	Biotin
Folic Acid

Major Elements

Calcium	Magnesium	Phosphorus	Sodium, Potassium, Chloride
Sulfur (Sulfer)

Trace Elements

Boron	Chromium	Cobalt	Copper
Fluorine	Iodine	Iron	Manganese
Molybdenum	Nickel (Nickle)	Selenium	Silicon
Tin	Vanadium	Zinc	Ultra Trace

Toxic Elements

Aluminum	Arsenic	Cadmium	Lead
Mercury