{"title":"寄生虫的异种生物转化系统。与相似宿主系统的相似和不同[新]。","authors":"L P Smirnov, E V Borvinskaya, I V Suhovskaya","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>The three phases system xenobiotic biotransformation in cells as prokaryotes as eukaryotes\nwas formed during the process of evolution. Clear and managed function of all three\nlinks of this system guarantee the survival of living organisms at alteration of chemical\ncomponent of environment. Oxidation, reduction or hydrolysis of xenobiotics realize in\nphase I by insertion or opening reactive and hydrophilic groups in structure of drug molecule.\nIn phase II xenobiotics or their metabolites from phase I conjugate with endogenic\ncompounds, main of there are glutathione, glucuronic acid, amino acids and sulphates.\nActive transport of substrata, metabolites and conjugates through cell lipid membranes\nspecial transport proteins carry out (phase III).\nThe system of xenobiotics biotransformation of helminths has essential differences\nfrom the same of vertebrate hosts. In particular, parasites do not reveal the activity of prime\noxidases of phase I, such as CYP or FMO, in spite of the genes of these enzymes in\nDNA. As this phenomenon displays mainly in adult helminths, living in guts of vertebrates,\nthen the hypothesis was formulated that this effect is related with adaptation to conditions\nof strong deficiency of oxygen, arise in a process of evolution (Kotze et al., 2006).\nLiterature data testify the existence in helminths of unique forms of enzymes of phase\nII, the investigation of which present doubtless interest in relation with possible role in\nadaptation to parasitic mode of life. Notwithstanding that many of helminths GST in greater\nor lesser degree similar with enzymes of M, P, S and О classes of other organisms, nevertheless\nthey have essential structural differences as compared with enzymes of hosts\nthat makes perspective the search of specific anthelminthics vaccines.\nTransport of xenobiotics is now considered phase III of biotransformation. It was\nshown that proteins of this phase (ATP binding cassette transporters (ABC ) of parasites)\nplay a key role in efflux of lipophilic xenobiotics, hydrophilic metabolites and conjugates\nand take part in forming of anthelminthics resistance. Some of these transporters, such as\nP-glycoprotein (Pgp), are important for drug resistance of helminths. In particular, a correlation\nbetween the level of expression of Pgp and resistance of S. mansoni and F. hepatica\nto widely used anthelminthics as praziquantel and triclabendazol exist.</p>","PeriodicalId":76305,"journal":{"name":"Parazitologiia","volume":"50 6","pages":"432-45"},"PeriodicalIF":0.0000,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[THE SYSTEM OF XENOBIOTICS BIOTRANSFORMATION OF HELMINTHS. RESEMBLANCE AND DIFFERENSES FROM SIMILAR HOST SYSTEMS (REWEW)].\",\"authors\":\"L P Smirnov, E V Borvinskaya, I V Suhovskaya\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The three phases system xenobiotic biotransformation in cells as prokaryotes as eukaryotes\\nwas formed during the process of evolution. Clear and managed function of all three\\nlinks of this system guarantee the survival of living organisms at alteration of chemical\\ncomponent of environment. Oxidation, reduction or hydrolysis of xenobiotics realize in\\nphase I by insertion or opening reactive and hydrophilic groups in structure of drug molecule.\\nIn phase II xenobiotics or their metabolites from phase I conjugate with endogenic\\ncompounds, main of there are glutathione, glucuronic acid, amino acids and sulphates.\\nActive transport of substrata, metabolites and conjugates through cell lipid membranes\\nspecial transport proteins carry out (phase III).\\nThe system of xenobiotics biotransformation of helminths has essential differences\\nfrom the same of vertebrate hosts. In particular, parasites do not reveal the activity of prime\\noxidases of phase I, such as CYP or FMO, in spite of the genes of these enzymes in\\nDNA. As this phenomenon displays mainly in adult helminths, living in guts of vertebrates,\\nthen the hypothesis was formulated that this effect is related with adaptation to conditions\\nof strong deficiency of oxygen, arise in a process of evolution (Kotze et al., 2006).\\nLiterature data testify the existence in helminths of unique forms of enzymes of phase\\nII, the investigation of which present doubtless interest in relation with possible role in\\nadaptation to parasitic mode of life. Notwithstanding that many of helminths GST in greater\\nor lesser degree similar with enzymes of M, P, S and О classes of other organisms, nevertheless\\nthey have essential structural differences as compared with enzymes of hosts\\nthat makes perspective the search of specific anthelminthics vaccines.\\nTransport of xenobiotics is now considered phase III of biotransformation. It was\\nshown that proteins of this phase (ATP binding cassette transporters (ABC ) of parasites)\\nplay a key role in efflux of lipophilic xenobiotics, hydrophilic metabolites and conjugates\\nand take part in forming of anthelminthics resistance. Some of these transporters, such as\\nP-glycoprotein (Pgp), are important for drug resistance of helminths. 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引用次数: 0
摘要
原核生物和真核生物在进化过程中形成了三个阶段的异种生物转化系统。这一系统的三个环节的清晰和有序的功能保证了生物在环境化学成分发生变化时的生存。异种生物的氧化、还原或水解是通过在药物分子结构中插入或打开活性基团和亲水基团来实现的。在第二相中,外源药物或其代谢产物与内源性化合物结合,主要有谷胱甘肽、葡萄糖醛酸、氨基酸和硫酸盐。通过细胞脂膜进行基质、代谢物和偶联物的主动运输,以及特殊的运输蛋白(III期)。蠕虫的异种生物转化系统与脊椎动物宿主的异种生物转化系统有本质区别。特别是,寄生虫没有显示第一阶段的原氧化酶的活性,如CYP或FMO,尽管这些酶的基因在dna中。由于这种现象主要表现在生活在脊椎动物内脏中的成年蠕虫身上,因此提出了一种假设,即这种效应与进化过程中出现的对强烈缺氧条件的适应有关(Kotze et al., 2006)。文献资料证明,在蠕虫体内存在独特形式的阶段ii酶,对这种酶的研究无疑与对寄生生活方式的可能角色不适应有关。尽管许多寄生虫的GST与其他生物的M、P、S和О类的酶或多或少相似,但与宿主的酶相比,它们具有本质的结构差异,这使得寻找特定的驱虫药疫苗成为可能。外源性药物的运输现在被认为是生物转化的第三阶段。研究表明,这一阶段的蛋白质(寄生虫的ATP结合盒转运蛋白(ABC))在亲脂外源物、亲水代谢物和偶联物的外排中起关键作用,并参与抗虫性的形成。其中一些转运体,如asp -糖蛋白(Pgp),对蠕虫的耐药性很重要。特别是,Pgp的表达水平与广泛应用于吡喹酮和三氯苯达唑等杀虫剂的曼氏s.m ansoni和肝形f.h atcato的耐药性存在相关性。
[THE SYSTEM OF XENOBIOTICS BIOTRANSFORMATION OF HELMINTHS. RESEMBLANCE AND DIFFERENSES FROM SIMILAR HOST SYSTEMS (REWEW)].
The three phases system xenobiotic biotransformation in cells as prokaryotes as eukaryotes
was formed during the process of evolution. Clear and managed function of all three
links of this system guarantee the survival of living organisms at alteration of chemical
component of environment. Oxidation, reduction or hydrolysis of xenobiotics realize in
phase I by insertion or opening reactive and hydrophilic groups in structure of drug molecule.
In phase II xenobiotics or their metabolites from phase I conjugate with endogenic
compounds, main of there are glutathione, glucuronic acid, amino acids and sulphates.
Active transport of substrata, metabolites and conjugates through cell lipid membranes
special transport proteins carry out (phase III).
The system of xenobiotics biotransformation of helminths has essential differences
from the same of vertebrate hosts. In particular, parasites do not reveal the activity of prime
oxidases of phase I, such as CYP or FMO, in spite of the genes of these enzymes in
DNA. As this phenomenon displays mainly in adult helminths, living in guts of vertebrates,
then the hypothesis was formulated that this effect is related with adaptation to conditions
of strong deficiency of oxygen, arise in a process of evolution (Kotze et al., 2006).
Literature data testify the existence in helminths of unique forms of enzymes of phase
II, the investigation of which present doubtless interest in relation with possible role in
adaptation to parasitic mode of life. Notwithstanding that many of helminths GST in greater
or lesser degree similar with enzymes of M, P, S and О classes of other organisms, nevertheless
they have essential structural differences as compared with enzymes of hosts
that makes perspective the search of specific anthelminthics vaccines.
Transport of xenobiotics is now considered phase III of biotransformation. It was
shown that proteins of this phase (ATP binding cassette transporters (ABC ) of parasites)
play a key role in efflux of lipophilic xenobiotics, hydrophilic metabolites and conjugates
and take part in forming of anthelminthics resistance. Some of these transporters, such as
P-glycoprotein (Pgp), are important for drug resistance of helminths. In particular, a correlation
between the level of expression of Pgp and resistance of S. mansoni and F. hepatica
to widely used anthelminthics as praziquantel and triclabendazol exist.