Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Nat Rev Nephrol. 2024 Dec;20(12):771-788. doi: 10.1038/s41581-024-00872-8. Epub 2024 Aug 28.
Amino acids form peptides and proteins and are therefore considered the main building blocks of life. The kidney has an important but under-appreciated role in the synthesis, degradation, filtration, reabsorption and excretion of amino acids, acting to retain useful metabolites while excreting potentially harmful and waste products from amino acid metabolism. A complex network of kidney transporters and enzymes guides these processes and moderates the competing concentrations of various metabolites and amino acid products. Kidney amino acid metabolism contributes to gluconeogenesis, nitrogen clearance, acid-base metabolism and provision of fuel for tricarboxylic acid cycle and urea cycle intermediates, and is thus a central hub for homeostasis. Conversely, kidney disease affects the levels and metabolism of a variety of amino acids. Here, we review the metabolic role of the kidney in amino acid metabolism and describe how different diseases of the kidney lead to aberrations in amino acid metabolism. Improved understanding of the metabolic and communication routes that are affected by disease could provide new mechanistic insights into the pathogenesis of kidney diseases and potentially enable targeted dietary or pharmacological interventions.
氨基酸形成肽和蛋白质,因此被认为是生命的主要组成部分。肾脏在氨基酸的合成、降解、过滤、重吸收和排泄中具有重要但未被充分认识的作用,它既能保留有用的代谢物,又能排泄氨基酸代谢产生的潜在有害和废物。肾脏转运蛋白和酶的复杂网络指导这些过程,并调节各种代谢物和氨基酸产物的竞争浓度。肾脏氨基酸代谢有助于糖异生、氮清除、酸碱代谢以及为三羧酸循环和尿素循环中间产物提供燃料,因此是体内平衡的中心枢纽。相反,肾脏疾病会影响多种氨基酸的水平和代谢。在这里,我们综述了肾脏在氨基酸代谢中的代谢作用,并描述了肾脏的不同疾病如何导致氨基酸代谢异常。更好地了解受疾病影响的代谢和通讯途径,可能为肾脏疾病的发病机制提供新的机制见解,并有可能实现针对饮食或药物的干预。