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水飞蓟宾和苯扎氯铵对黄嘌呤脱氢酶和黄嘌呤氧化酶可逆及不可逆形式的抑制动力学。

Kinetics of the inhibition of xanthine dehydrogenase and of the reversible and irreversible forms of xanthine oxidase by silibinin and bendazac.

出版信息

Environ Toxicol Pharmacol. 1996 Jul 15;1(4):279-84. doi: 10.1016/1382-6689(96)00021-X.

DOI:10.1016/1382-6689(96)00021-X
PMID:21781693
Abstract

Xanthine oxidase exists in vivo predominantly as a NAD(+)-dependent dehydrogenase form (xanthine dehydrogenase) which can be transformed into oxygen-dependent oxidase forms as a result of sulfhydryl oxidation (reversible xanthine oxidase) or proteolysis (irreversible xanthine oxidase). Xanthine oxidase has been hypothesized to be a potential source of oxygen-derived free radicals during reperfusion of ischemic tissues. Xanthine dehydrogenase was purified from rat liver and converted into reversible xanthine oxidase by heating at 37 °C and into irreversible xanthine oxidase by proteolysis with trypsin. Silibinin and bendazac are compounds used in therapeutics and to which free radical scavenging properties were ascribed. The effects of the compounds silibinin and bendazac on the different forms of the enzyme were studied. Silibinin inhibited all the forms of the enzyme but bendazac inhibited only reversible and irreversible xanthine oxidase. The inhibitions seem to be mixed non-competitive-competitive. The authors discuss the hypothesis that selective inhibitors of xanthine oxidase, preventing the interruption of uric acid formation, may have some advantage over the inhibitors of both xanthine dehydrogenase and xanthine oxidase in the treatment and prevention of situations such as ischemia and reperfusion syndromes.

摘要

黄嘌呤氧化酶在体内主要以 NAD(+)依赖的脱氢酶形式(黄嘌呤脱氢酶)存在,由于巯基氧化(可逆黄嘌呤氧化酶)或蛋白水解(不可逆黄嘌呤氧化酶),可以转化为依赖氧的氧化酶形式。黄嘌呤氧化酶被假设为缺血组织再灌注期间氧自由基的潜在来源。黄嘌呤脱氢酶从大鼠肝脏中纯化,并通过在 37°C 下加热转化为可逆黄嘌呤氧化酶,通过胰蛋白酶蛋白水解转化为不可逆黄嘌呤氧化酶。水飞蓟宾和苯扎氯铵是用于治疗的化合物,并被归因于自由基清除特性。研究了化合物水飞蓟宾和苯扎氯铵对酶的不同形式的影响。水飞蓟宾抑制所有形式的酶,但苯扎氯铵仅抑制可逆和不可逆黄嘌呤氧化酶。抑制似乎是混合的非竞争-竞争性。作者讨论了这样一种假设,即选择性黄嘌呤氧化酶抑制剂可防止尿酸形成中断,在治疗和预防缺血和再灌注综合征等情况时,可能比同时抑制黄嘌呤脱氢酶和黄嘌呤氧化酶的抑制剂具有一些优势。

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1
Kinetics of the inhibition of xanthine dehydrogenase and of the reversible and irreversible forms of xanthine oxidase by silibinin and bendazac.水飞蓟宾和苯扎氯铵对黄嘌呤脱氢酶和黄嘌呤氧化酶可逆及不可逆形式的抑制动力学。
Environ Toxicol Pharmacol. 1996 Jul 15;1(4):279-84. doi: 10.1016/1382-6689(96)00021-X.
2
Changes in the xanthine dehydrogenase/xanthine oxidase ratio in the rat kidney subjected to ischemia-reperfusion stress: preventive effect of some flavonoids.缺血再灌注应激大鼠肾脏中黄嘌呤脱氢酶/黄嘌呤氧化酶比值的变化:某些黄酮类化合物的预防作用
Res Commun Chem Pathol Pharmacol. 1992 Nov;78(2):211-8.
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[Is xanthine oxidase a universal source of superoxide radicals in ischemic and reperfusion lesions?].[黄嘌呤氧化酶是缺血及再灌注损伤中超氧阴离子自由基的普遍来源吗?]
Biull Eksp Biol Med. 1990 Jun;109(6):548-50.
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Xanthine oxidase: a critical mediator of myocardial injury during ischemia and reperfusion?黄嘌呤氧化酶:缺血再灌注期间心肌损伤的关键介质?
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Conversion of xanthine dehydrogenase to oxidase in ischemic rat tissues.缺血大鼠组织中黄嘌呤脱氢酶向氧化酶的转化。
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Metabolism of isovanillin by aldehyde oxidase, xanthine oxidase, aldehyde dehydrogenase and liver slices.异香草醛在醛氧化酶、黄嘌呤氧化酶、醛脱氢酶和肝切片中的代谢
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N-Hydroxyguanidine compound 1-(3,4-dimethoxy- 2-chlorobenzylideneamino)-3-hydroxyguanidine inhibits the xanthine oxidase mediated generation of superoxide radical.N-羟基胍化合物1-(3,4-二甲氧基-2-氯亚苄基氨基)-3-羟基胍抑制黄嘌呤氧化酶介导的超氧阴离子自由基的生成。
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The physiology of endothelial xanthine oxidase: from urate catabolism to reperfusion injury to inflammatory signal transduction.内皮黄嘌呤氧化酶的生理学:从尿酸分解代谢到再灌注损伤再到炎症信号转导
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The conversion of xanthine dehydrogenase to xanthine oxidase and the role of the enzyme in reperfusion injury.黄嘌呤脱氢酶向黄嘌呤氧化酶的转化以及该酶在再灌注损伤中的作用。
J Biochem. 1994 Jul;116(1):1-6. doi: 10.1093/oxfordjournals.jbchem.a124480.

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