Cationic amino acid transporters and their modulation by nitric oxide in cardiac muscle cells.
Cationic amino acid transporters and their modulation by nitric oxide in cardiac muscle cells.
复制标题
心肌细胞中的阳离子氨基酸转运蛋白及其一氧化氮的调节。
DOI：
10.1007/s12551-021-00870-1
复制
发表时间：
2021
影响因子：
--
通讯作者：
Peluffo,RDaniel
中科院分区：
文献类型：
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作者：
Peluffo,RDaniel
阳离子氨基酸转运蛋白（CATs）在向细胞内一氧化氮合酶（NOS）提供底物L-精氨酸中起核心作用，NOS是负责合成一氧化氮（NO）的酶。在心脏中，心肌细胞产生的NO对心肌收缩力具有不同的甚至相反的作用，这取决于其产生的亚细胞位置。大约十年前，使用生物物理和生物化学方法的组合，我们发现并表征了在心肌细胞质膜中同时起作用的高亲和力和低亲和力CAT。后来，我们报道了NO对心脏CATs活性的负反馈调节。以这种方式，发现NO通过调节可用作NOS底物的L-精氨酸的量来调节其自身的生物合成。我们最近解决了这种NO调节低亲和力高容量CAT-2A的分子决定因素。本文综述了L-精氨酸转运蛋白的一些生物物理和生化特征及其与心肌生理和病理的潜在关系。
Cationic amino acid transporters (CATs) play a central role in the supply of the substrate L-arginine to intracellular nitric oxide synthases (NOS), the enzymes responsible for the synthesis of nitric oxide (NO). In heart, NO produced by cardiac myocytes has diverse and even opposite effects on myocardial contractility depending on the subcellular location of its production. Approximately a decade ago, using a combination of biophysical and biochemical approaches, we discovered and characterized high- and low-affinity CATs that function simultaneously in the cardiac myocyte plasma membrane. Later on, we reported a negative feedback regulation of NO on the activity of cardiac CATs. In this way, NO was found to modulate its own biosynthesis by regulating the amount of L-arginine that becomes available as NOS substrate. We have recently solved the molecular determinants for this NO regulation on the low-affinity high-capacity CAT-2A. This review highlights some biophysical and biochemical features of L-arginine transporters and their potential relation to cardiac muscle physiology and pathology.