Department of Urology, Wake Forest University Medical Center, Winston-Salem, NC 27157, USA.
Metabolism. 2011 Jul;60(7):950-6. doi: 10.1016/j.metabol.2010.09.002. Epub 2010 Oct 30.
Experiments in humans and rodents using oral doses of glycine and phenylalanine have suggested that the metabolism of these amino acids contributes to urinary oxalate excretion. To better define this contribution, we have examined the primed, constant infusion of [1-(13)C(1)] phenylalanine and [1,2-(13)C(2)] glycine in the postabsorptive state in healthy adults. Subjects were infused for 5 hours, hourly urines were collected, and blood was drawn every 30 minutes. Ion chromatography/mass spectrometry was used to measure [(13)C] enrichment in urinary oxalate, glycolate, and hippurate; and the enrichment of (13)C-amino acids in plasma samples was measured by gas chromatography/mass spectrometry. Following infusion with either 6 μmol/(kg h) [1-(13)C(1)] phenylalanine or 6 μmol/(kg h) [1,2-(13)C(2)] glycine, no isotopic glycolate or oxalate was detected in urine. Based on the limits of detection of our ion chromatography/mass spectroscopy method, these data indicate that less than 0.7% of the urinary oxalate could be derived from phenylalanine catabolism and less than 5% from glycine catabolism. Infusions with high levels of [1,2-(13)C(2)] glycine, 60 μmol/(kg h), increased mean plasma glycine by 29% and the whole-body flux of glycine by 72%. Under these conditions, glycine contributed 16.0% ± 1.6% and 16.6% ± 3.2% to urinary oxalate and glycolate excretion, respectively. Experiments using cultured hepatoma cells demonstrated that only at supraphysiological levels (>1 mmol/L) did glycine and phenylalanine metabolism increase oxalate synthesis. These data suggest that glycine and phenylalanine metabolism make only minor contributions to oxalate synthesis and urinary oxalate excretion.
在人体和啮齿动物中进行的口服甘氨酸和苯丙氨酸实验表明,这些氨基酸的代谢有助于尿草酸盐的排泄。为了更好地定义这种贡献,我们在健康成年人的吸收后状态下检查了[1-(13)C(1)]苯丙氨酸和[1,2-(13)C(2)]甘氨酸的脉冲恒速输注。受试者输注 5 小时,每小时收集尿液,并每 30 分钟采集一次血液。离子色谱/质谱法用于测量尿草酸盐、乙二醇酸盐和 hippurate 中的[(13)C]丰度;并通过气相色谱/质谱法测量血浆样品中(13)C-氨基酸的丰度。在输注 6 μmol/(kg h)[1-(13)C(1)]苯丙氨酸或 6 μmol/(kg h)[1,2-(13)C(2)]甘氨酸后,尿液中未检测到同位素乙二醇酸盐或草酸盐。根据我们的离子色谱/质谱法方法的检测限,这些数据表明,尿草酸盐中只有不到 0.7%来自苯丙氨酸代谢,不到 5%来自甘氨酸代谢。输注高浓度[1,2-(13)C(2)]甘氨酸(60 μmol/(kg h))可使血浆甘氨酸水平升高 29%,甘氨酸全身通量增加 72%。在这些条件下,甘氨酸分别贡献 16.0%±1.6%和 16.6%±3.2%到尿草酸盐和乙二醇酸盐的排泄中。使用培养的肝癌细胞进行的实验表明,只有在超生理水平(>1 mmol/L)下,甘氨酸和苯丙氨酸代谢才会增加草酸盐的合成。这些数据表明,甘氨酸和苯丙氨酸代谢对草酸盐合成和尿草酸盐排泄的贡献很小。