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终末期肾病中的谷氨酰胺动力学与蛋白质周转

Glutamine kinetics and protein turnover in end-stage renal disease.

作者信息

Raj Dominic S C, Welbourne Tomas, Dominic Elizabeth A, Waters Debra, Wolfe Robert, Ferrando Arny

机构信息

Division of Nephrology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131-5271, USA.

出版信息

Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E37-46. doi: 10.1152/ajpendo.00240.2004. Epub 2004 Jul 20.

Abstract

Alanine and glutamine constitute the two most important nitrogen carriers released from the muscle. We studied the intracellular amino acid transport kinetics and protein turnover in nine end-stage renal disease (ESRD) patients and eight controls by use of stable isotopes of phenylalanine, alanine, and glutamine. The amino acid transport kinetics and protein turnover were calculated with a three-pool model from the amino acid concentrations and enrichment in the artery, vein, and muscle compartments. Muscle protein breakdown was more than synthesis (nmol.min(-1).100 ml leg(-1)) during hemodialysis (HD) (169.8 +/- 20.0 vs. 125.9 +/- 21.8, P < 0.05) and in controls (126.9 +/- 6.9 vs. 98.4 +/- 7.5, P < 0.05), but synthesis and catabolism were comparable pre-HD (100.7 +/- 15.7 vs. 103.4 +/- 14.8). Whole body protein catabolism decreased by 15% during HD. The intracellular appearance of alanine (399.0 +/- 47.1 vs. 243.0 +/- 34.689) and glutamine (369.7 +/- 40.6 vs. 235.6 +/- 27.5) from muscle protein breakdown increased during dialysis (nmol.min(-1).100 ml leg(-1), P < 0.01). However, the de novo synthesis of alanine (3,468.9 +/- 572.2 vs. 3,140.5 +/- 467.7) and glutamine (1,751.4 +/- 82.6 vs. 1,782.2 +/- 86.4) did not change significantly intradialysis (nmol.min(-1).100 ml leg(-1)). Branched-chain amino acid catabolism (191.8 +/- 63.4 vs. -59.1 +/- 42.9) and nonprotein glutamate disposal (347.0 +/- 46.3 vs. 222.3 +/- 43.6) increased intradialysis compared with pre-HD (nmol.min(-1).100 ml leg(-1), P < 0.01). The mRNA levels of glutamine synthase (1.45 +/- 0.14 vs. 0.33 +/- 0.08, P < 0.001) and branched-chain keto acid dehydrogenase-E2 (3.86 +/- 0.48 vs. 2.14 +/- 0.27, P < 0.05) in the muscle increased during HD. Thus intracellular concentrations of alanine and glutamine are maintained during HD by augmented release of the amino acids from muscle protein catabolism. Although muscle protein breakdown increased intradialysis, the whole body protein catabolism decreased, suggesting central utilization of amino acids released from skeletal muscle.

摘要

丙氨酸和谷氨酰胺是从肌肉释放的两种最重要的氮载体。我们通过使用苯丙氨酸、丙氨酸和谷氨酰胺的稳定同位素,研究了9名终末期肾病(ESRD)患者和8名对照者的细胞内氨基酸转运动力学和蛋白质周转情况。氨基酸转运动力学和蛋白质周转是根据动脉、静脉和肌肉隔室中的氨基酸浓度和富集情况,用三池模型计算得出的。在血液透析(HD)期间(169.8±20.0对125.9±21.8,P<0.05)以及在对照者中(126.9±6.9对98.4±7.5,P<0.05),肌肉蛋白质分解超过合成(nmol·min⁻¹·100 ml腿部⁻¹),但在HD前合成和分解代谢相当(100.7±15.7对103.4±14.8)。HD期间全身蛋白质分解代谢下降了15%。透析期间,肌肉蛋白质分解产生的丙氨酸(399.0±47.1对243.0±34.689)和谷氨酰胺(369.7±40.6对235.6±27.5)的细胞内出现量增加(nmol·min⁻¹·100 ml腿部⁻¹,P<0.01)。然而,丙氨酸(3468.9±572.2对3140.5±467.7)和谷氨酰胺(1751.4±82.6对1782.2±86.4)的从头合成在透析期间没有显著变化(nmol·min⁻¹·100 ml腿部⁻¹)。与HD前相比,透析期间支链氨基酸分解代谢(191.8±63.4对-59.1±42.9)和非蛋白质谷氨酸处置(347.0±46.3对222.3±43.6)增加(nmol·min⁻¹·100 ml腿部⁻¹,P<0.01)。HD期间肌肉中谷氨酰胺合成酶(1.45±0.14对0.33±0.08,P<0.001)和支链酮酸脱氢酶-E2(3.86±0.48对2.14±0.27,P<0.05)的mRNA水平升高。因此,HD期间通过增加肌肉蛋白质分解代谢中氨基酸的释放来维持细胞内丙氨酸和谷氨酰胺的浓度。尽管透析期间肌肉蛋白质分解增加,但全身蛋白质分解代谢下降,提示骨骼肌释放的氨基酸被中枢利用。

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