Department of Biology and Interdepartmental Laboratory for Electron Microscopy, University Roma Tre, Via della Vasca Navale 79, I-00146 Roma, Italy.
Biochem Biophys Res Commun. 2011 Jul 22;411(1):185-9. doi: 10.1016/j.bbrc.2011.06.130. Epub 2011 Jun 24.
Ferrous human serum heme-albumin (HSA-heme-Fe(II)) displays globin-like properties. Here, the effect of ibuprofen and warfarin on kinetics of HSA-heme-Fe(II) nitrosylation is reported. Values of the second-order rate constant for HSA-heme-Fe(II) nitrosylation (k(on)) decrease from 6.3 × 10(6)M(-1)s(-1) in the absence of drugs, to 4.1 × 10(5)M(-1)s(-1) and 4.8 × 10(5)M(-1)s(-1), in the presence of saturating amounts of ibuprofen and warfarin, respectively, at pH 7.0 and 20.0°C. From the dependence of k(on) on the drug concentration, values of the dissociation equilibrium constant for ibuprofen and warfarin binding to HSA-heme-Fe(II) (i.e., K=3.2 × 10(-3)M and 2.6 × 10(-4)M, respectively) were determined. The observed allosteric effects could indeed reflect ibuprofen and warfarin binding to the regulatory fatty acid binding site FA2, which brings about an alteration of heme coordination, slowing down HSA-heme-Fe(II) nitrosylation. Present data highlight the allosteric modulation of HSA-heme-Fe(II) reactivity by heterotropic effectors.
亚铁人血清血红素白蛋白（HSA-heme-Fe(II)）表现出球蛋白样性质。本文报道了布洛芬和华法林对 HSA-heme-Fe(II)亚硝化为动力学的影响。在没有药物的情况下，HSA-heme-Fe(II)亚硝化为二级反应速率常数（k(on)）的值为 6.3×10(6)M(-1)s(-1)，而在 pH7.0 和 20.0°C 时，存在饱和量的布洛芬和华法林时，其值分别降低至 4.1×10(5)M(-1)s(-1)和 4.8×10(5)M(-1)s(-1)。根据 k(on)对药物浓度的依赖性，确定了布洛芬和华法林与 HSA-heme-Fe(II)结合的离解平衡常数（即 K=3.2×10(-3)M 和 2.6×10(-4)M）。观察到的变构效应确实可能反映了布洛芬和华法林与调节性脂肪酸结合位点 FA2 的结合，这导致了血红素配位的改变，从而减缓了 HSA-heme-Fe(II)的亚硝化为。目前的数据强调了变构调节剂对 HSA-heme-Fe(II)反应性的变构调节。
