IMPLICATION OF NONENZYMATIC GLYCOSYLATION AS A MODE OF DAMAGE IN DIETARY COPPER DEFICIENCY

The purpose of this study was to determine whether nonenzymatic glycos ylation of proteins (glycation) could be implicated in the defects ass ociated with dietary copper deficiency. Male, weanling Sprague-Dawley rats were fed for 5 weeks diets that were adequate (5 ppm) or deficien t in Cu (similar to 0.5 ppm). Half of each group were given daily intr aperitoneal injections of aminoguanidine, which inhibits glycation bey ond formation of the Amadori product. Copper deficiency caused cardiac enlargement, anemia, enhanced production of thiobarbituric acid react ive substances (TBARS) in the heart and enhanced percentage of glycate d hemoglobin (Hb A(1)), Aminoguanidine ameliorated the cardiac enlarge ment and anemia but had no effect on TBARS production or hemoglobin gl ycation caused by copper deficiency. The enhanced percentage of Hb A(1 ) suggests that generalized protein glycation occurs in copper-deficie nt rats, The higher TBARS production in copper deficiency indicates th at the peroxidation reported to be associated with glycation is occurr ing. The amelioration of cardiac enlargement and anemia of copper defi ciency by aminoguanidine suggests that glucose-induced cross linking o f proteins and their degradation into advanced glycosylation endproduc ts may contribute to those defects.