苯扎贝特和氯贝酸对人亚铁血红蛋白一氧化氮衍生物光谱性质的影响。

Effect of bezafibrate and clofibric acid on the spectroscopic properties of the nitric oxide derivative of ferrous human hemoglobin.

作者信息

Ascenzi P, Coletta M, Desideri A, Polizio F, Bertollini A, Santucci R, Amiconi G

机构信息

Department of Pharmaceutical Chemistry and Technology, University of Turin, Italy.

出版信息

J Inorg Biochem. 1992 Oct 1;48(1):47-53. doi: 10.1016/0162-0134(92)80052-w.

DOI:10.1016/0162-0134(92)80052-w

PMID:1326599

Abstract

The effect of bezafibrate (BZF) and clofibric acid (CFA) on the spectroscopic (EPR and absorbance) properties of the nitric oxide derivative of ferrous human hemoglobin (HbNO) has been investigated quantitatively. In the presence of BZF and CFA, the X-band EPR spectra and the absorption spectra in the Soret region of HbNO display the same basic characteristics described in the presence of inositol hexakisphosphate (IHP) and 2, 3-diphosphoglycerate (2,3-DPG). Next, in the presence of these allosteric effectors, the oxygen affinity for ferrous human hemoglobin (Hb) is reduced. These findings indicate that BZF and CFA, as already reported for IHP and 2, 3-DPG, induce the stabilization of a low affinity conformation of the ligated hemoprotein (i.e., HbNO). Values of the apparent equilibrium constant for BZF and CFA binding to HbNO (K) are 1.5(+/- 0.2) x 10(-2) M and 2.8(+/- 0.3) x 10(-2) M, respectively, at pH 7.0 (in 0.1 M N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid]/NaOH buffer system plus 0.1 M NaCl) and 20 degrees C. The results reported here represent clearcut evidence for BZF and CFA specific (i.e., functionally relevant) binding to a ligated derivative of Hb (i.e., HbNO).

摘要

已对苯扎贝特（BZF）和氯贝酸（CFA）对人亚铁血红蛋白（Hb）的一氧化氮衍生物（HbNO）光谱性质（电子顺磁共振和吸光度）的影响进行了定量研究。在BZF和CFA存在的情况下，HbNO的X波段电子顺磁共振光谱和索雷特区域的吸收光谱显示出与肌醇六磷酸（IHP）和2,3 - 二磷酸甘油酸（2,3 - DPG）存在时所描述的相同基本特征。其次，在这些变构效应剂存在的情况下，人亚铁血红蛋白（Hb）对氧气的亲和力降低。这些发现表明，BZF和CFA如同已报道的IHP和2,3 - DPG一样，诱导连接的血红蛋白（即HbNO）低亲和力构象的稳定。在pH 7.0（于0.1 M N - [2 - 羟乙基]哌嗪 - N' - [2 - 乙磺酸]/NaOH缓冲体系加0.1 M NaCl）和20℃条件下，BZF和CFA与HbNO结合的表观平衡常数（K）值分别为1.5（±0.2）×10⁻² M和2.8（±0.3）×10⁻² M。此处报道的结果为BZF和CFA与Hb的连接衍生物（即HbNO）的特异性（即功能相关）结合提供了明确证据。