体内
肌红蛋白
化学
血红蛋白
血红素蛋白
一氧化碳
离体
可溶性鸟苷酰环化酶
生物物理学
鸟苷酸环化酶
血红素
体外
生物化学
细胞生物学
作者
Wen Lu,Xiaoxiao Yang,Binghe Wang
标识
DOI:10.1016/j.bcp.2022.115041
摘要
The endogenous signaling roles of carbon monoxide (CO) have been firmly established at the pathway level. For CO’s molecular mechanism(s) of actions, hemoproteins are generally considered as possible targets. Importantly, soluble guanylyl cyclase (sGC) is among the most widely referenced molecular targets. However, the affinity of CO for sGC (K d : 240 μM) is much lower than for other highly abundant hemoproteins in the body, such as myoglobin (K d : 29 nM) and hemoglobin (K d : 0.7 nM-4.5 μM), which serve as CO reservoirs. Further, most of the mechanistic studies involving sGC activation by CO were based on in-vitro or ex-vivo studies using CO concentrations not readily attenable in vivo and in the absence of hemoglobin as a competitor in binding. As such, whether such in-vitro/ex-vivo results can be directly extrapolated to in-vivo studies is not clear because of the need for CO to be transferred from a high-affinity binder (e.g., hemoglobin) to a low-affinity target if sGC is to be activated in vivo . In this review, we discuss literature findings of sGC activation by CO and the experimental conditions; examine the myths in the disconnect between the low affinity of sGC for CO and the reported activation of sGC by CO; and finally present several possibilities that may lead to additional studies to improve our understanding of this direct CO-sGC axis, which is yet to be convincingly established as playing generally critical roles in CO signaling in vivo .
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