Hydroxyproline ingestion and urinary oxalate and glycolate excretion

Hydroxyproline ingestion and urinary oxalate and glycolate excretion
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DOI:
10.1038/sj.ki.5001906
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发表时间:
2006-12-01
影响因子:
19.6
通讯作者:
Holmes, R. P.
Holmes, R. P.
中科院分区:
医学1区
文献类型:
--
作者:
Knight, J.;Jiang, J.;Holmes, R. P.

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内源性草酸盐合成是草酸钙结石形成和原发性高尿酸相关肾损害的重要因素。虽然草酸盐的主要前体被认为是乙醛酸,但在人体中导致乙醛酸合成的途径并没有很好的定义。羟脯氨酸是胶原蛋白的组成氨基酸,是潜在的乙醛酸前体。我们研究了膳食中来源于明胶的羟脯氨酸对尿草酸和乙醇酸排泄的贡献。在控制草酸盐饮食上比较了对摄入30 g明胶或乳清蛋白的反应。测定10 g明胶负荷的代谢时程以及对不同明胶负荷的反应。明胶饮食组的尿乙醇酸排泄量是乳清饮食组的5.3倍,尿草酸排泄量高出43%。在5和10 g明胶负荷下观察到血浆羟脯氨酸和尿草酸盐和乙醇酸盐的显著变化,但在1和2 g负荷下未观察到。将这些结果外推至每日预期胶原蛋白周转和羟脯氨酸摄入量表明,羟脯氨酸代谢贡献了20-50%的经尿液排泄的乙醇酸和5-20%的源自内源性合成的尿草酸。我们的研究结果还表明,肾脏吸收了大量的羟脯氨酸和乙醇酸,它们在该组织中代谢为草酸盐值得进一步考虑。
Endogenous synthesis of oxalate is an important contributor to calcium oxalate stone formation and renal impairment associated with primary hyperoxaluria. Although the principal precursor of oxalate is believed to be glyoxylate, pathways in humans resulting in glyoxylate synthesis are not well defined. Hydroxyproline, a component amino acid of collagen, is a potential glyoxylate precursor. We have investigated the contribution of dietary hydroxyproline derived from gelatin to urinary oxalate and glycolate excretion. Responses to the ingestion of 30 g of gelatin or whey protein were compared on controlled oxalate diets. The time course of metabolism of a 10 g gelatin load was determined as well as the response to varying gelatin loads. Urinary glycolate excretion was 5.3-fold higher on the gelatin diet compared to the whey diet and urinary oxalate excretion was 43% higher. Significant changes in plasma hydroxyproline and urinary oxalate and glycolate were observed with 5 and 10 g gelatin loads, but not 1 and 2 g loads. Extrapolation of these results to daily anticipated collagen turnover and hydroxyproline intake suggests that hydroxyproline metabolism contributes 20-50% of glycolate excreted in urine and 5-20% of urinary oxalate derived from endogenous synthesis. Our results also revealed that the kidney absorbs significant quantities of hydroxyproline and glycolate, and their metabolism to oxalate in this tissue warrants further consideration.