Submitted to: International Symposium on Metal Ions in Biology and Medicine
Publication Type: Proceedings
Publication Acceptance Date: May 7, 2000
Publication Date: May 31, 2000
Citation: Nielsen, F.H., Yokoi, K., Uthus, E.O. 2000. Marginal dietary pyridoxine and supplemental dietary homocystine and methionine affect the response of the rat to nickel deprivation. Proceedings of the 6th International Symposium on Metal Ions in Biology and Medicine, San Juan, Puerto Rico, May 7-10, 2000. 6:524-527. Interpretive Summary: Previous studies in our laboratory have shown that the response of rats to nickel deprivation is altered by vitamin B12, folic acid and pyridoxine (B6) deficiency. All of these vitamins influence the metabolism of homocysteine, a form of amino acid which has been associated with heart disease when amounts in blood are increased. Thus, an experiment was conducted to ascertain whether high intakes homocystine (an amino acid composed of two homocysteine molecules), and methionine (an amino acid that can be converted into homocysteine in the body), could be used as dietary stressors to enhance or alter the signs of nickel deprivation and thereby provide clues as to whether nickel has a biochemical function that could indicate that this element is of nutritional importance to humans. Because vitamin B6 is important in the metabolism of homocysteine, feeding deficient amounts of this vitamin was also used as a dietary stressor. Findings were obtained which showed that high dietary homocystine and methionine and low dietary vitamin B6 affect the response of rats to nickel deprivation. The findings also indicated several possible sites where nickel is biochemically important. Further study of these possibilities is still needed to ascertain more specifically the nutritional importance of nickel, but the findings in the present study support the concept that nickel is an essential nutrient whose lack could affect lipid and protein metabolism in higher animals and humans.
Technical Abstract: Previous studies in our laboratory have shown that the response of rats to nickel (Ni) deprivation is altered by vitamin B12, folic acid, and pyridoxine (B6) deficiency. All of these vitamins influence the metabolism of homocysteine. Thus, an experiment was conducted to ascertain whether the reduced form of homocysteine, or homocystine (Hcy), and the in vivo precursor of homocysteine, methionine (Met), could be used as dietary stressors to enhance or alter the signs of Ni deprivation and thereby provide clues as the biochemical function of Ni in higher animals. Because B6 is important in the metabolism of homocysteine, it was also included as a dietary stressor. The experiment was a 2 x 2 x 3 factorially arranged with Ni supplemented at 0 and 1 mg/kg diet, B6 supplemented at 0 and 7.5 mg/kg diet, and dietary amino acid supplements of none, 10 g/kg Hcy and 10 g/kg Met. The basal diet contained about 8 ng Ni, 1.8 mg B6 and 4.7 g of Met per kg. An interaction between Ni and sulfur amino acid supplementation affected plasma pyridoxal 5'-phosphate (PLP) and triglyceride concentration, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Both ALT and AST activities were decreased in Ni-deficient, and increased in Ni-supplemented rats in response to amino acid supplementation. Nickel deficiency increased plasma triglyceride concentrations. This increase was most evident in rats supplemented with Met or Hcy because the amino acid supplements increased plasma triglyceride concentrations in Ni-deficient rats. The findings show that rats fed Ni in amounts found in natural diets respond differently than rats fed very low amounts of Ni when fed diets high in sulfur amino acids and low in B6. Thus, Ni most likely is of nutritional importance.