Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-10T09:32:36.220Z Has data issue: false hasContentIssue false

Cobalt-vitamin B12 deficiency causes accumulation of odd- numbered, branched-chain fatty acids in the tissues of sheep

Published online by Cambridge University Press:  09 March 2007

D. G. Kennedy
Affiliation:
1Veterinary Sciences Division, Department of Agriculture for Northern Ireland, Stormont, Berfast BT4 3SD, Northern Ireland
S. Kennedy
Affiliation:
1Veterinary Sciences Division, Department of Agriculture for Northern Ireland, Stormont, Berfast BT4 3SD, Northern Ireland
W. J. Blanchflower
Affiliation:
1Veterinary Sciences Division, Department of Agriculture for Northern Ireland, Stormont, Berfast BT4 3SD, Northern Ireland
J. M Scott
Affiliation:
2Trinity College, Dublin, Republic of Ireland
D. G. Weir
Affiliation:
2Trinity College, Dublin, Republic of Ireland
A. M. Molloy
Affiliation:
2Trinity College, Dublin, Republic of Ireland
P. B. Young
Affiliation:
1Veterinary Sciences Division, Department of Agriculture for Northern Ireland, Stormont, Berfast BT4 3SD, Northern Ireland
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Nine 5-month-old lambs were randomly allocated to two groups and were fed on either a Co-deficient whole-barley diet (n 5), or the same diet supplemented with Co (n 4). The lambs were fed on their respective diets for 28 weeks. Plasma vitamin B12 concentrations fell below the lower limit of normality after 6 weeks, and plasma methylmalonic acid (MMA) concentrations rose above the upper limit of normality after 10 weeks. However, plasma MMA concentrations fell to near normal levels towards the end of the experiment suggesting that diagnosis of more severe Co deficiency based on determination of plasma MMA concentrations may be of limited value. Analysis of tissue samples collected at slaughter revealed a marked reduction in the vitamin B12 concentration and the activity of methylmalonyl-CoA mutase (EC 5.4.99.2) in the tissues taken from the Co-deficient sheep, by comparison with the controls. Although tissue concentrations of MMA in the Co-deficient animals were not significantly different from those of the controls, we did detect increased concentrations of branched-chain fatty acids. This suggested that misincorporation of MMA, but not propionic acid, into fatty acids had occurred. The Co-deficient lambs did not develop any neurological signs, suggesting that accumulation of branched-chain fatty acids may not be involved in the development of neurological lesions.

Type
Interactions between vitamins and lipid metabolism
Copyright
Copyright © The Nutrition Society 1994

References

REFERENCES

Bergman, E. N., Roe, W. E. & Kon, K. (1966). Quantitative aspects of propionate metabolism and gluconeogenesis in sheep. American Journal of Physiology 211, 793799.CrossRefGoogle ScholarPubMed
Blanchflower, W. J., Cannavan, A. & Kennedy, D. G. (1990). Determination of trace amounts of cobalt in feed grains and forages by solvent extraction and graphite furnace atomic absorption spectrometry. Analyst 115, 13231325.CrossRefGoogle ScholarPubMed
Duncan, W. R. H., Morrison, R. & Garton, G. A. (1981). Effects of cobalt deficiency in pregnant and post- parturient ewes and their lambs. British Journal of Nutrition 46, 331344.CrossRefGoogle ScholarPubMed
Folch, J., Lees, M. & Sloane-Stanley, G. M. (1957). A simple method for the isolation and purification of total lipids from animal tissues. Journal of Biologica1 Chemistry 226, 497509.CrossRefGoogle ScholarPubMed
Frenkel, E. P. (1973). Abnormal fatty acid metabolism in peripheral nerves of patients with pernicious anemia. Journal of Clinical Investigation 52, 12371245.CrossRefGoogle ScholarPubMed
Frenkel, E. P., Kitchens, R. L. & Johnston, J. M. (1973). The effect of vitamin B12 deprivation on the enzymes of fatty acid synthesis. Journal of Biological Chemistry 248, 75407546.CrossRefGoogle ScholarPubMed
Kennedy, D. G., Blanchflower, W. J., Scott, J. M., Weir, D. G., Molloy, A. M., Kennedy, S. & Young, P. B. (1992 a). Cobalt-vitamin B-12 deficiency decreases methionine synthase activity and phospholipid methylation in the sheep. Journal of Nutrition 122, 13861390.CrossRefGoogle ScholarPubMed
Kennedy, D. G., Blanchflower, W. J., Young, P. B. & Davidson, W. B. (1992 b). Development and application of an α-face specific radioimmunoassay for vitamin B12. Biological Trace Element Research 35, 153156.CrossRefGoogle ScholarPubMed
Kennedy, D. G., Cannavan, A., Molloy, A., O'Harte, F., Taylor, S. M., Kennedy, S. & Blanchflower, W. J. (1990 a). The activity of methylmalonyl CoA mutase (EC 5.4.99.2) and methionine synthetase ( EC 2.1.1.13) in the tissues of cobalt-vitamin B12 deficient sheep. British Journal of Nutrition 64, 721732.CrossRefGoogle ScholarPubMed
Kennedy, D. G., O'Harte, F. P. M., Blanchflower, W. J. & Rice, D. A. (1990 b). Development of a specific radioimmunoassay for vitamin B12 and its application in the diagnosis of cobalt deficiency in sheep. Veterinary Research Comniunications 14, 255265.CrossRefGoogle ScholarPubMed
Kennedy, D. G., OHarte, F. P. M., Blanchflower, W. J. & Rice, D. A. (1991 a). Sequential changes in propionate metabolism during the development of cobalt/vitamin B12 deficiency in sheep. Biological Trace Element Research 28, 233241.CrossRefGoogle ScholarPubMed
Kennedy, D. G., Young, P. B., McCaughey, W. J., Kennedy, S. & Blanchflower, W. J. (1991 b). Rumen succinate production may ameliorate the effects of cobalt-vitamin B-12 deficiency on methylmalonyl CoA mutase in sheep. Journal of Nutrition 121, 12361242.CrossRefGoogle ScholarPubMed
Kishimoto, Y., Williams, M., Moser, H. W., Hignite, C. & Biermann, K. (1973). Branched-chain and odd- numbered fatty acids and aldehydes in the nervous system of a patient with deranged vitamin B12 metabolism. Journal of Lipid Research 14, 69 77.CrossRefGoogle Scholar
Kovachy, R. J., Copley, S. D. & Allen, R. H. (1983). Recognition, isolation and characterization of rat liver D-methylmalonyl Coenzyme A hydrolase. Journal of Biological Chemistry 258, 1141511421.CrossRefGoogle ScholarPubMed
McMurray, C. H., Blanchflower, W. J., Rice, D. A. & McLoughlin, M. F. (1986). Sensitive and specific gas chromatographic method for the determination of methylmalonic acid in the plasma and urine of ruminants. Journal of Chromatography Biomedical Applications 378, 201207.CrossRefGoogle ScholarPubMed
Marston, H. R. (1970). The requirement of sheep for cobalt or for vitamin B12. British Journal of Nutririon 24, 615633.CrossRefGoogle ScholarPubMed
Millar, K. R. & Lorentz, P. P. (1979). Urinary methylmalonic acid as an indicator of the vitamin B12 status of grazing sheep. New Zealand Veterinary Journal 27, 9092.CrossRefGoogle ScholarPubMed
O'Harte, F. P. M., Kennedy, D. G., Blanchflower, W. J. & Rice, D. A. (1989). Methylmalonic acid in the diagnosis of cobalt deficiency in barley fed lambs. British Journal of Nutrition 62, 729738.CrossRefGoogle ScholarPubMed
Ramsey, R. B., Scott, T. & Banik, N. L. (1977). Fatty acid composition of myelin isolated from the brain of a patient with cellular deficiency of co-enzyme forms of vitamin B-12. Journal of Neurological Science 34, 221232.CrossRefGoogle Scholar
Scaife, J. R., Wahle, K. W. J. & Carton, G. A. (1978). Utilization of methylmalonate for the synthesis of branched-chain fatty acids by preparations of chicken liver and sheep adipose tissue. Biochemical Journal 176, 799804.CrossRefGoogle ScholarPubMed
Smith, R. M., Osborne-White, W. S. & Russell, G. R. (1969). Methylmalonic acid and Coenzyme A concentrations in the livers of pair-fed vitamin B12-deficient and vitamin B12-treated sheep. Biochemical Journal 112, 703707.CrossRefGoogle Scholar
Ulvund, M. J. (1990). Ovine White Liver Disease (OWLD). Vitamin B12 and methyl malonic acid estimations in blood. Acta Vererinuriae Scandinaviae 31, 267275.CrossRefGoogle ScholarPubMed
Weir, D. G., Keating, S., Molloy, A., McPartlin, J., Kennedy, S., Blanchflower, W. J., Kennedy, D. G., Rice, D. A. & Scott, J. M. (1988). Methylation deficiency causes vitamin B12 associated neuropathy in the pig. Journal of Neurochemistry 51, 19491952.CrossRefGoogle ScholarPubMed