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다량의 엽산 보충이 비타민 $B_{12}$가 결핍된 쥐의 엽산 대사과정에 미치는 영향
민혜선,최준호,Min, Hye-Seon,Choe, Joon-Ho 생화학분자생물학회 1993 한국생화학회지 Vol.26 No.8
비타민 $B_{12}$의 결핍으로 인해 엽산의 생화학적인 기능이 저하되는 기작을 조사하기 위하여 비타민 $B_{12}$가 결핍된 흰쥐에게 다량의 엽산을(200mg/kg 식이) 공급한 후 간에 있어서의 엽산의 함량, non-methyl folate의 함량, pteroyl-polyglutamate 직쇄길이의 분포상태를 분석하였다. 뇨중 다량의 methylmalonic acid를 배설하는, 비타민 $B_{12}$가 심하게 결핍된 쥐에게 다량의 엽산을 보충시켰을 때 간내의 엽산함량은 정상치를 회복하였으나, 히스티딘의 산화속도를 통해 측정되는 엽산의 생화학적 기능은 회복되지 않았다. 간장내 non-methyl folate의 함량도 엽산보충에 의해 정상수준으로 증가되었으므로 non-methyl folate의 절대 함량이 엽산의 생화학적인 활성을 결정하는 주된 요인이 아닌 것으로 나타났다. 엽산의 polyglutamate 직쇄의 분포는 다량의 엽산보충에 의해 다소 짧아졌으나, 대부분 5개 이상의 glutamate를 결함하고 있는 것으로 나타났으므로 비타민 $B_{12}$가 결핍된 쥐의 히스티딘의 산화속도가 낮은 원인이 엽산의 polyglutamate 직쇄길이가 짧아지는데에 기인하지 않음을 알 수 있었다. 이 결과로부터 $H_4$PteGlu/5-methyl-$H_4$ PteGlu의 비율이 polyglutamate 직쇄분포보다 엽산의 생화학적 기능을 변화시키는 더 중요한 요인으로 보인다. Effect of supplementation of high levels of folate (200 mg of folate per kg of diet) to vitamin $B_{12}$-deficient rats was studied. Increased total liver folate levels were observed in the vitamin $B_{12}$-deficient rats supplemented with high levels of folate although folate supplementation had no significant effect on normalizing the rate of histidine oxidation and the urinary formiminoglutamate excretion. Supplementation of high levels of folate to vitamin $B_{12}$-deficient rats increased hepatic non-methyl folate levels to normal or supranormal levels and shifted the polyglutamate chain distribution of folate derivatives slightly decreased. However, penta- and hexa-glutamate derivatives of non-methyl folates were found predominantly in the liver of both vitamin $B_{12}$-deficient and vitamin $B_{12}$-supplemented rats in this study. Thus the absolute hepatic levels of total folate or $H_4$PteGlu were not strictly related with the rate of histidine oxidation and the low rate of histidine oxidation in vitamin $B_{12}$-deficient rats supplemented with high levels of folate were not due to the reduced length of polyglutamate chain of folate derivatives. These data suggest that the ratio of $H_4$PteGlu/5-methyl-$H_4$PteGlu may be the more important factor in modifying folate functions and the methyl folate trap may not be circumvented by supplementation of high levels of folate in vitamin $B_{12}$-deficient animals.
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다량의 엽산 보충이 비타민 B12가 결핍된 쥐의 엽산 대사과정에 미치는 영향
민혜선,최준호 ( Hye Seon Min,Joon Ho Choe ) 생화학분자생물학회 1993 BMB Reports Vol.26 No.8
Effect of supplementation of high levels of folate (200 ㎎ of folate per ㎏ of diet) to vitamin B_(12)-deficient rats was studied. Increased total liver folate levels were observed in the vitamin B_(12)-deficient rats supplemented with high levels of folate although folate supplementation had no significant effect on normalizing the rate of histidine oxidation and the urinary formiminoglutamate excretion. Supplementation of high levels of folate to vitamin B_(12)-deficient rats increased hepatic non-methyl folate levels to normal or supranormal levels and shifted the polyglutamate chain distribution of folate derivatives slightly decreased. However, penta- and hexa-glutamate derivatives of non-methyl folates were found predominantly in the liver of both vitamin B_(12)-deficient and vitamin B_(12)-supplemented rats in this study. Thus the absolute hepatic levels of total folate or H₄PteGlu were not strictly related with the rate of histidine oxidation and the low rate of histidine oxidation in vitamin B_(12)-deficient rats supplemented with high levels of folate were not due to the reduced length of polyglutamate chain of folate derivatives. These data suggest that the ratio of H₄PteGlu/5-methyl-H₄PteGlu may be the more important factor in modifying folate functions and the methylfolate trap may not be circumvented by supplementation of high levels of folate in vitamin B_(12)-deficient animals.
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