Carbon monoxide (CO) has been firmly established as an endogenous signaling molecule with a variety of pathophysiological and pharmacological functions, including immunomodulation, organ protection, and circadian clock regulation, among many others. In terms of its molecular mechanism(s) of action, CO is known to bind to a large number of hemoproteins with at least 25 identified targets, including hemoglobin, myoglobin, neuroglobin, cytochrome c oxidase, cytochrome P450, soluble guanylyl cyclase, myeloperoxidase, and some ion channels with dissociation constant values spanning the range of sub-nM to high μM. Although CO’s binding affinity with a large number of targets has been extensively studied and firmly established, there is a pressing need to incorporate such binding information into the analysis of CO’s biologic response in the context of affinity and dosage. Especially important is to understand the reservoir role of hemoglobin in CO storage, transport, distribution, and transfer. We critically review the literature and inject a sense of quantitative assessment into our analyses of the various relationships among binding affinity, CO concentration, target occupancy level, and anticipated pharmacological actions. We hope that this review presents a picture of the overall landscape of CO’s engagement with various targets, stimulates additional research, and helps to move the CO field in the direction of examining individual targets in the context of all of the targets and the concentration of available CO. We believe that such work will help the further understanding of the relationship of CO concentration and its pathophysiological functions and the eventual development of CO-based therapeutics.

中文翻译：

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一氧化碳信号传导：在结合亲和力、浓度和生物反应的背景下检查其与各种分子靶标的结合

一氧化碳 (CO) 已被牢固地确立为一种内源性信号分子，具有多种病理生理学和药理学功能，包括免疫调节、器官保护和生物钟调节等。就其作用分子机制而言，已知CO可与大量血红素蛋白结合，并具有至少25个已确定的靶标，包括血红蛋白、肌红蛋白、神经红蛋白、细胞色素c氧化酶、细胞色素P450、可溶性鸟苷酸环化酶、髓过氧化物酶、一些离子通道的解离常数值涵盖亚纳摩尔级到高微米级M. 尽管 CO 与大量靶标的结合亲和力已得到广泛研究并得到牢固确立，但迫切需要将此类结合信息纳入亲和力和剂量背景下 CO 生物反应的分析中。尤其重要的是了解血红蛋白在二氧化碳储存、运输、分配和转移中的储存作用。我们批判性地回顾了文献，并将定量评估的意义融入到我们对结合亲和力、CO浓度、目标占据水平和预期药理作用之间的各种关系的分析中。我们希望这篇综述能够描绘出 CO 与各种目标合作的总体情况，激发更多的研究，