Both arginine (Arg) and its precursor citrulline (Cit) have received much interest in the past two decades because of their potential effects on whole‐body nitric oxide (NO) production and augmentation of NO‐dependent signalling pathways. However, the usefulness of Arg supplementation for NO production is questionable because of its high splanchnic first pass metabolism (FPM), which limits its systemic availability. Both hepatic‐ and extrahepatic arginases critically limit the availability of Arg for the NO synthase enzymes (NOSs) and therefore, a limited amount of oral Arg can reach the systemic circulation for NO synthesis. Arg also has some undesired effects including induction of arginase activity, an increase of urea levels, a decrease of cellular uptake of Cit and decrease of recycling of Arg from Cit. In contrast, Cit has more availability as an NO precursor because of its high intestinal absorption, low FPM and high renal reabsorption. At the cellular level, co‐localization of Cit transport systems and the enzymes involved in the Cit‐Arg‐NO pathway facilitates channelling of Cit into NO. Furthermore, cells preferably use Cit rather than either intra‐ or extracellular Arg to improve NO output, especially in high‐demand situations. In conclusion, available evidence strongly supports the concept that Cit leads to higher NO production and suggests that Cit may have a better therapeutic effect than Arg for NO‐disrupted conditions.

中文翻译：

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一氧化氮内源性通量：瓜氨酸优于精氨酸

在过去的二十年中，精氨酸 (Arg) 及其前体瓜氨酸 (Cit) 都受到了广泛关注，因为它们对全身一氧化氮 (NO) 的产生和增强 NO 依赖性信号通路的潜在影响。然而，由于内脏首过代谢 (FPM) 高，限制了其全身可用性，因此补充 Arg 对 NO 生产的有用性值得怀疑。肝内精氨酸酶和肝外精氨酸酶都严重限制了 NO 合酶 (NOS) Arg 的可用性，因此，有限量的口服精氨酸可以到达全身循环以进行 NO 合成。Arg 还具有一些不良作用，包括诱导精氨酸酶活性、尿素水平增加、细胞对 Cit 的吸收减少和从 Cit 回收 Arg 的减少。相比之下，由于其高肠道吸收、低 FPM 和高肾重吸收，Cit 作为 NO 前体的可用性更高。在细胞水平上，Cit 转运系统和参与 Cit-Arg-NO 途径的酶的共定位促进了 Cit 转化为 NO。此外，细胞优选使用 Cit 而不是细胞内或细胞外 Arg 来提高 NO 输出，尤其是在高需求情况下。总之，现有证据强烈支持 Cit 导致更高 NO 产生的概念，并表明 Cit 可能比 Arg 对 NO 干扰条件具有更好的治疗效果。Cit 转运系统和参与 Cit-Arg-NO 途径的酶的共定位促进了 Cit 进入 NO 的通道。此外，细胞优选使用 Cit 而不是细胞内或细胞外 Arg 来提高 NO 输出，尤其是在高需求情况下。总之，现有证据强烈支持 Cit 导致更高 NO 产生的概念，并表明 Cit 可能比 Arg 对 NO 干扰条件具有更好的治疗效果。Cit 转运系统和参与 Cit-Arg-NO 途径的酶的共定位促进了 Cit 进入 NO 的通道。此外，细胞优选使用 Cit 而不是细胞内或细胞外 Arg 来提高 NO 输出，尤其是在高需求情况下。总之，现有证据强烈支持 Cit 导致更高 NO 产生的概念，并表明 Cit 可能比 Arg 对 NO 干扰条件具有更好的治疗效果。