Folate and homocysteine metabolism in copper-deficient rats.
To investigate the effect of copper deficiency on folate and homocysteine metabolism, we measured plasma, red-cell and hepatic folate, plasma homocysteine and vitamin B-12 concentrations, and hepatic methionine synthase activities in rats. Two groups of male Sprague-Dawley rats were fed semi-purified diets containing either 0. 1 mg (copper-deficient group) or 9.2 mg (control group) of copper per kg. After 6 weeks of dietary treatment, copper deficiency was established as evidenced by markedly decreased plasma and hepatic copper concentrations in rats fed the low-copper diet. Plasma, red-cell, hepatic folate, and plasma vitamin B-12 concentrations were similar in both groups, whereas plasma homocysteine concentrations in the copper-deficient group were significantly higher than in the control group (P<0.05). Copper deficiency resulted in a 21% reduction in hepatic methionine synthase activity as compared to the control group (P<0.01). This change most likely caused the increased hepatic 5-methyltetrahydrofolate and plasma homocysteine concentrations in the copper-deficient group. Our results indicate that hepatic methionine synthase may be a cuproenzyme, and plasma homocysteine concentrations are influenced by copper nutriture in rats. These data support the concept that copper deficiency can be a risk factor for cardiovascular disease.
Tamura
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T
Department of Nutrition Sciences, 218 Webb Bldg., University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. tamurat@uab.edu
Hong
K H
KH
Mizuno
Y
Y
Johnston
K E
KE
Keen
C L
CL
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism; D000818:Animals; D003300:Copper / Q000097:blood / Q000172:deficiency*; D004912:Erythrocytes / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism*; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013763:Tetrahydrofolates / Q000378:metabolism; D014805:Vitamin B 12 / Q000097:blood
D013763:Tetrahydrofolates; D006710:Homocysteine; D003300:Copper; D005492:Folic Acid; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D014805:Vitamin B 12