Hepatic alanine-glyoxylate aminotransferase activity and oxalate metabolism in vitamin B6 deficient rats
Hepatic alanine-glyoxylate aminotransferase activity and oxalate metabolism in vitamin B6 deficient rats
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DOI：
10.1016/s0022-5347(05)63992-4
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发表时间：
2003-02-01
影响因子：
6.6
通讯作者：
Ogawa, Y
中科院分区：
文献类型：
--
作者：
Nishijima, S;Sugaya, K;Ogawa, Y
目的：尿草酸在草酸钙结石的形成中起重要作用，约50%~60%的尿草酸来源于乙醛的内源性代谢。乙醛酸在肝脏中被丙氨酸-乙醛酸氨基转移酶酶促转化为甘氨酸，维生素B6作为辅酶起着关键作用。因此，我们评估了维生素B6缺乏大鼠肝脏丙氨酸乙醛转氨酶活性和草酸代谢。材料和方法：雄性Wistar大鼠12只，喂养正常饲料和维生素B6缺乏饲料。结果：维生素B6缺乏组大鼠尿中草酸/肌酐、乙醇酸/肌酐、甘氨酸/肌酐、甘氨酸/肌酐比值明显高于对照组，甘氨酸/肌酐、柠檬酸/肌酐比值显著低于对照组。维生素B6缺乏大鼠肝组织丙氨酸乙醛转氨酶活性及其mRNA水平显著低于对照组。结论：维生素B6缺乏不仅降低丙氨酸乙醛转氨酶活性，而且下调肝细胞丙氨酸乙醛转氨酶基因表达，导致高草酸尿症和高乙醇酸尿症，继发草酸前体代谢受损。在维生素B6缺乏症中，高草酸尿伴低柠檬酸尿症也可能导致草酸钙结石的形成。
Purpose: Urinary oxalate has an important role in the formation of calcium oxalate stone and approximately 50% to 60% of urinary oxalate is derived from the endogenous metabolism of glyoxylate. Glyoxylate is enzymatically converted to glycine by alanine-glyoxylate aminotransferase in the liver and vitamin B6 has a key role as a coenzyme. Therefore, we evaluated hepatic alanine-glyoxylate aminotransferase activity and oxalate metabolism in vitamin B6 deficient rats.Materials and Methods: A total of 12 male Wistar rats were fed a control or a vitamin B6 deficient diet. After 4 weeks creatinine, oxalate, glycolate, glycine and citrate in the urine, and alanine-glyoxylate aminotransferase activity and its mRNA level in the liver were measured.Results: Urinary oxalate-to-creatinine and glycolate-to-creatinine ratios were significantly higher in vitamin B6 deficient rats than in control rats but urinary glycine-to-creatinine and citrate-to-creatinine ratios were significantly lower. Hepatic alanine-glyoxylate aminotransferase activity and its mRNA level were significantly lower in vitamin B6 deficient rats than in control rats.Conclusions: Vitamin B6 deficiency not only decreased alanine-glyoxylate aminotransferase activity, but also down-regulated alanine-glyoxylate aminotransferase gene expression by hepatocytes and led to hyperoxaluria and hyperglycolic aciduria secondary to impaired metabolism of oxalate precursors. Hyperoxaluria with hypocitruria may also contribute to calcium oxalate stone formation in vitamin B6 deficiency.