采用密度泛函理论(DFT)对P450酶活性中心铁卟啉Cpd I催化二乙基亚硝胺(NDEA)代谢活化的反应机理进行了研究.结果表明,Cpd I催化NDEA羟基化的过程包含氢抽提反应和回弹反应2个步骤.其中,氢抽提反应为控速步骤,氢自由基从NDEA转移到铁卟啉...采用密度泛函理论(DFT)对P450酶活性中心铁卟啉Cpd I催化二乙基亚硝胺(NDEA)代谢活化的反应机理进行了研究.结果表明,Cpd I催化NDEA羟基化的过程包含氢抽提反应和回弹反应2个步骤.其中,氢抽提反应为控速步骤,氢自由基从NDEA转移到铁卟啉的Fe O上,是典型的氢原子传递(HAT)过程;紧接着铁卟啉上的羟基经历无能垒的反应过程回弹到NDEA自由基上,形成羟基化代谢产物.NDEA羟基化过程中高自旋态(HS)和低自旋态(LS)均参与反应,整个羟基化过程呈现明显的双态反应性(TSR).研究比较了NDEA分子侧链上Cα—H和Cβ—H羟基化反应的差异,得到Cα—H和Cβ—H羟基化所需跨越的能垒分别为57.7/57.7 k J/mol(LS/HS)和76.4/74.3 k J/mol(LS/HS),表明Cα—H比Cβ—H更易于在P450作用下发生羟基化;此外,Cβ—H羟基化所需克服的能垒并未过高,使得Cβ—H羟基化在生理条件下完全也有可能发生.本研究为深入揭示亚硝胺经代谢活化导致癌症的作用机制提供了可靠的理论依据.展开更多
A total of 32 cases of aseptic femoral head necrosis were treated with long needle combined with herbal medicines. Huantiao (GB 30), Weizhong (BL 40), Chengshan (BL 57), etc. were punctured with 3 cun, 7 cun, and 2.5 ...A total of 32 cases of aseptic femoral head necrosis were treated with long needle combined with herbal medicines. Huantiao (GB 30), Weizhong (BL 40), Chengshan (BL 57), etc. were punctured with 3 cun, 7 cun, and 2.5 chi, long thick needles. Herbal medicines used were Danggui (当归 Radix Angelicae Sinensis), Huangqi (黄芪 Radix Astragali seu Hedysari), Gouji (狗脊 Rhizoma Cibotii), etc.. Following 2 months to 3 years’ treatment, of the 32 cases, 16 were cured, 10 had remarkable improvement, 5 experienced improvement in the symptoms and signs and one failed in the treatment.展开更多
文摘采用密度泛函理论(DFT)对P450酶活性中心铁卟啉Cpd I催化二乙基亚硝胺(NDEA)代谢活化的反应机理进行了研究.结果表明,Cpd I催化NDEA羟基化的过程包含氢抽提反应和回弹反应2个步骤.其中,氢抽提反应为控速步骤,氢自由基从NDEA转移到铁卟啉的Fe O上,是典型的氢原子传递(HAT)过程;紧接着铁卟啉上的羟基经历无能垒的反应过程回弹到NDEA自由基上,形成羟基化代谢产物.NDEA羟基化过程中高自旋态(HS)和低自旋态(LS)均参与反应,整个羟基化过程呈现明显的双态反应性(TSR).研究比较了NDEA分子侧链上Cα—H和Cβ—H羟基化反应的差异,得到Cα—H和Cβ—H羟基化所需跨越的能垒分别为57.7/57.7 k J/mol(LS/HS)和76.4/74.3 k J/mol(LS/HS),表明Cα—H比Cβ—H更易于在P450作用下发生羟基化;此外,Cβ—H羟基化所需克服的能垒并未过高,使得Cβ—H羟基化在生理条件下完全也有可能发生.本研究为深入揭示亚硝胺经代谢活化导致癌症的作用机制提供了可靠的理论依据.
文摘A total of 32 cases of aseptic femoral head necrosis were treated with long needle combined with herbal medicines. Huantiao (GB 30), Weizhong (BL 40), Chengshan (BL 57), etc. were punctured with 3 cun, 7 cun, and 2.5 chi, long thick needles. Herbal medicines used were Danggui (当归 Radix Angelicae Sinensis), Huangqi (黄芪 Radix Astragali seu Hedysari), Gouji (狗脊 Rhizoma Cibotii), etc.. Following 2 months to 3 years’ treatment, of the 32 cases, 16 were cured, 10 had remarkable improvement, 5 experienced improvement in the symptoms and signs and one failed in the treatment.
