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氨基酸的肾脏转运

Renal transport of amino acids.

作者信息

Silbernagl S

出版信息

Klin Wochenschr. 1979 Oct 1;57(19):1009-19. doi: 10.1007/BF01479986.

Abstract

According to recent experimental data the renal transport of amino acids (AA) is characterized as follows. 1. Kinetics: Several reabsorption systems remove AA from the tubular fluid by active transport with Michaelis-Menten type kinetics. Passive diffusion does play only a relatively small role in reabsorption, but determines the pump leak steady state concentration at the end of the tubule. 2. Stereospecificity: Except for aspartate the naturally occurring L-analogs show a much larger affinity to the transport "carriers" than the D-isomers do. 3. Specificity: Separate transport mechanisms exist for a) the "acidic" AA (Glu and Asp); b) the "dibasic" AA (Arg, Lys, Orn); c) cystine/cystine; d) the "imino" acids (Pro, OH-Pro and other N-substituted AA); e) the beta- and gamma-AA (beta-Ala, GABA, Taurine); f) all other "neutral" AA. For the group (d) and maybe also for (b) and glycine additional low capacity/high affinity systems exist. 4. Localization: Except for glycine and taurine under normal conditions more than 80% of the filtered load are reabsorbed within the first third of the proximal tubule. At an elevated load the rest of the proximal tubule (including pars recta) but not the distal nephron is included into the reabsorptive process. AA are also taken up from the peritubular blood. 5. Energy sources: At least the main part of AA uptake at the brushborder membrane is dependent from a transmembranal Na+-gradient which in turn is established by the ATP driven Na+-pumps at the basolateral side of the cell (Secondary active transport or co-transport of AA). 6. Biochemistry: The biochemical nature of the AA-"carriers" is unknown. The recent hypothesis than a "gamma-glutamyl cycle" plays a major role in this context has been disproved to great extent. 7. Peptides: Oligopeptides (Angiotensin, Gluthathion) filtered at the glomerulum are hydrolyzed by brushborder peptidases within the tubule lumen. The splitting products, the free constituent amino acids, are reabsorbed subsequently by their respective transport systems.

摘要

根据最近的实验数据,氨基酸(AA)的肾脏转运具有以下特点。1. 动力学:几种重吸收系统通过具有米氏动力学类型的主动转运从肾小管液中清除氨基酸。被动扩散在重吸收中仅起相对较小的作用,但决定了肾小管末端的泵漏稳态浓度。2. 立体特异性:除天冬氨酸外,天然存在的L-类似物对转运“载体”的亲和力远大于D-异构体。3. 特异性:存在单独的转运机制用于:a)“酸性”氨基酸(谷氨酸和天冬氨酸);b)“碱性”氨基酸(精氨酸、赖氨酸、鸟氨酸);c)胱氨酸/半胱氨酸;d)“亚氨基酸”(脯氨酸、羟脯氨酸和其他N-取代氨基酸);e)β-和γ-氨基酸(β-丙氨酸、γ-氨基丁酸、牛磺酸);f)所有其他“中性”氨基酸。对于组(d),可能还有组(b)和甘氨酸,存在额外的低容量/高亲和力系统。4. 定位:在正常情况下,除甘氨酸和牛磺酸外,超过80%的滤过量在近端小管的前三分之一内被重吸收。在负荷增加时,近端小管的其余部分(包括直部)但不包括远端肾单位参与重吸收过程。氨基酸也从肾小管周围血液中摄取。5. 能量来源:至少在刷状缘膜处氨基酸摄取的主要部分依赖于跨膜Na+梯度,而该梯度又由细胞基底外侧的ATP驱动的Na+泵建立(氨基酸的继发性主动转运或协同转运)。6. 生物化学:氨基酸“载体”的生物化学性质尚不清楚。最近关于“γ-谷氨酰循环”在此过程中起主要作用的假说在很大程度上已被否定。7. 肽:在肾小球滤过的寡肽(血管紧张素、谷胱甘肽)在肾小管腔内被刷状缘肽酶水解。水解产物,即游离的组成氨基酸,随后通过各自的转运系统被重吸收。

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