Differential down-regulation and induction responses of testicular steroidogenic cytochromes P-450(cscc) and P-450(C17α) to human choriogonadotropin

Evidence is presented that the regulation of the cytochrome P-450(C17) of the steroid-17-monooxygenase and of the cytochrome P-450(cscc) of the cholesterolmonooxygenase by human choriogonadotropin (hCG)in vivo is mediated by differential mechanisms in the adult rat testis. An initial down-regulation of the cytochrome P-450(C17) but not of the P-450(cscc) can be demonstrated. Furthermore, induction of the cytochrome P-450(cscc) requires exposure to higher hCG doses (3270 of the maximal induction rate of 43.7 pmol/(testis x d) are achieved with 4 IU hCG/single dose) than induction of the P-450(C17) (59% of the maximal induction rate of 48.4 pmol/(testis x d) with 4 IU hCG/single dose), Finally, induction ofcytochrome P-450(cscc) starts faster after initiation of hCG treatment than induction of P-450(C 17).     

昆虫细胞色素P450研究:P450基因

细胞色素P450广泛存在于生物界,它因参与许多外来物质和内源性物质的代谢而具有十分重要的作用［1－5］细胞色素P450的研究大约有50多年的历史[3]。60年代的工作主要是对这一血红素蛋白的生物化学和生物物理学特征的了解以及膜结合P450酶系的酶学功能[3]。70年代的研究集中在细胞色素P450酶系的分离纯化及其活性的重组。纯化P450的成功证明了许多P450在物理学和酶学特征方面的不同,也为制备抗体及利用抗体来确定某种P450的存在与数量以及抑制特定P450的酶活性提供了手段,使进一步阐明P450的反应机制成为可能。80年代分子生物学技术的…     

Metabolism of anabolic steroids by recombinant human cytochrome P450 enzymes: Gas chromatographic–mass spectrometric determination of metabolites

Metabolism of steroid hormones with anabolic properties was studied in vitro using human recombinant CYP3A4, CYP2C9 and 2B6 enzymes. The enzyme formats used for CYP3A4 and CYP2C9 were insect cell microsomes expressing human CYP enzymes and purified recombinant human CYP enzymes in a reconstituted system. CYP3A4 enzyme formats incubated with anabolic steroids, testosterone, 17α-methyltestosterone, metandienone, boldenone and 4-chloro-1,2-dehydro-17α-methyltestosterone, produced 6β-hydroxyl metabolites identified as trimethylsilyl (TMS)-ethers by a gas chromatography–mass spectrometry (GC–MS) method. When the same formats of CYP2C9 were incubated with the anabolic steroids, no 6β-hydroxyl metabolites were formed. Human lymphoblast cell microsomes expressing human CYP2B6 incubated with the steroids investigated produced traces of 6β-hydroxyl metabolites with testosterone and 17α-methyltestosterone only. We suggest that the electronic effects of the 3-keto-4-ene structural moiety contribute to the selectivity within the active site of CYP3A4 enzyme resulting in selective 6β-hydroxylation.     

Fungal cytochrome P450 sterol 14α-demethylase (CYP51) and azole resistance in plant and human pathogens

Azoles have been applied widely to combat pathogenic fungi in medicine and agriculture and, consequently, loss of efficacy has occurred in populations of some species. Often, but not always, resistance was found to result from amino acid substitutions in the molecular target of azoles, 14α-sterol demethylase (CYP51 syn. ERG11). This review summarizes CYP51 function, evolution, and structure. Furthermore, we compare the occurrence and contribution of CYP51 substitutions to azole resistance in clinical and field isolates of important fungal pathogens. Although no crystal structure is available yet for any fungal CYP51, homology modeling using structures from other origins as template allowed deducing models for fungal orthologs. These models served to map amino acid changes known from clinical and field isolates. We conclude with describing the potential consequences of these changes on the topology of the protein to explain CYP51-based azole resistance. Knowledge gained from molecular modeling and resistance research will help to develop novel azole structures.     

19,20-EpDPE, a bioactive CYP450 metabolite of DHA monoacyglyceride, decreases Ca²⁺ sensitivity in human pulmonary arteries

The aim of this study was to investigate the effect of docosahexaenoic acid monoacylglyceride (MAG-DHA) on human pulmonary arterial tone. Tension measurements on pulmonary arterial tissues demonstrated that MAG-DHA reduced U-46619-induced tone, which is highly sensitive to the H-1152 inhibitor. Results also showed that MAG-DHA treatments decreased RhoA activity levels, which in turn inactivated the Rho-kinase pathway, leading to a reduction in U-46619-induced Ca(2+) sensitivity of permeabilized pulmonary artery smooth muscle cells. According to the mechanical responses assessing U-46619-induced Ca(2+) sensitivity in the absence or presence of 3 μM MAG-DHA, MAG-DHA plus 1 μM N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide (MS-PPOH, a cytochrome P-450 epoxygenase inhibitor) and 300 nM 19,20-epoxydocosapentaenoic acid (a cytochrome P-450 epoxygenase-dependent DHA metabolite), our data suggest that the MAG-DHA is metabolized in a bioactive epoxymetabolite. This epoxyeicosanoid in turn decreases active tone and Ca(2+) sensitivity of smooth muscles cells through an inhibition of the Rho-kinase pathway. Together, these data provide primary evidence regarding the mode of action of MAG-DHA in human pulmonary arteries and suggest that this compound may be of pharmacological interest in patients with pulmonary hypertension to generate intracellular bioactive metabolites.     

植物细胞色素P450

对植物细胞色素P450(CYP450)基因的分离,植物CYP450在苯丙烷类物质、芥子油苷及IAA和萜类等物质的生物合成中的功能,以及对天然生物合成与人工合成物质的解毒功能等研究进展作了简要的综述。指出分离植物细胞色素P450基因,并对其生物学功能进行分析以及植物细胞色素P450降解除草剂的机制及其在环境生物修复等方面的应用是今后一段时间内植物CYP450领域的研究热点。     

家蝇P-450基因研究进展

较细致地介绍了近年来家蝇P-450基因的研究进展,总结了目前已克隆的8个家蝇P-450基因在同源性、遗传多态性、基因结构、基因的表达与调控等方面的特点。     

昆虫细胞色素P450的研究:P450基因的进化

80年代分子生物学方法被用于分离和鉴定特定P450的CDNA或基因组克隆［‘］,至今已知的P450基因包括70个基因家族、127个亚家族的40O多个,基因序列的数量还在迅速增加I’］。不同P450间的进化关系在一些综述中都有涉及［”’,‘］,本文介绍这一主题的一些主要观点,重点放在P450功能的进化及其机制。亚细胞色素P450的基本特征及其分类与命名所有细胞色素P450具有一非共价结合的血红素和环绕高度保守的半跳氨酸的一段26氨基残基的保守序列,这一半跳氨酸提供血红素铁的第5个配体（ligand）。当血红素铁接受电子被还原后再与CO结合产…     

Paleopediatrics: Or when did human infants really become human?

Modern human children take about twice as long as their closest biological relative, the chimpanzee, to mature. One standard explanation for the evolution of “delayed maturation” at an early stage of human evolution is that it provided the time necessary for immature individuals to learn complex skills, most notably those relating to tool-making abilities. However, after comparing dental maturational profiles of early hominids from South Africa (who apparently did make and use stone tools) (Susman [1994] Science 265:1570–1573) to those of extant humans and chimpanzees, we find no evidence to document an association between “delayed maturation” and tool-making abilities in the early stages of human evolution. This also suggests that the assumed association between prolonged childhood dependency and other behaviors often associated with the advent of tool-making such as cooperative hunting, food sharing, home bases, sexual division of labor, etc., is also suspect. Instead, we must look for other, or additional, selective pressures for the evolution of “delayed maturation,” which may postdate the australopithecine radiation. © 1995 Wiley-Liss, Inc.     

昆虫细胞色素P450研究:P450酶系的可诱导性

细胞色素Ｐ４５０酶系是生物体中的一类重要的代谢酶系,它的一个重要特征是它的可诱导性［１］。自Ｂｒｏｗｎ等［２］发现一定的化合物可以促进ＭＦＯ的活性以来,诱导现象得到深入细致地研究,并成为了解Ｐ４５０分子遗传学的工具［３］。诱导是指通过暂时的、加速合成产生正常水平以上的附加蛋白的现象［４］。昆虫中诱导现象的首篇报道是ＡｇｏｓｉｎａｎｄＤｉｎａｍａｒｃａ［５］,他们发现施用ＤＤＴ于侵扰锥猎蝽Ｔｒｉａｔｏｍａｉｎｆｅｓｔａｎｓ（Ｋｌｎｇ）这种吸血昆虫时,昆虫的ＮＡＤＰ含量上升,后来Ｍｏｒｅｌｌｏ［６］…     

细胞色素P450的多样性

细胞色素Ｐ４５０的多样性＊邱星辉冷欣夫（中国科学院动物研究所,北京１０００８０）关键词细胞色素Ｐ４５０多样性细胞色素Ｐ４５０是一类以还原态与ＣＯ结合后在波长４５０ｎｍ处有吸收峰的含血红素的单链蛋白质［１～３］。它于１９５８年被发现以来,就引起了人们的...     

细胞色素P-450研究概况

肝细胞色素P-450是人及动物体内,代谢内源性及外源性化合物的一族酶,其氧化药物的机制已被进一步阐明,并发现P-450虽可使大多数外源性化合物代谢解毒,但也与某些药物的毒性作用以及化学致癌有关。现已证明,肝内有多种形式的P-450,分别为不同的诱导剂所诱导。它们在光谱特性、底物特异性以及催化反应等方面有明显的区别,并证明酶的诱导是由特定基因调节的。此外,近年来多种P-450的分离分析方法也有了一定的提高。     

细胞色素P-450研究概况

肝细胞色素P-450是人及动物体内,代谢内源性及外源性化合物的一族酶,其氧化药物的机制已被进一步阐明,并发现P-450虽可使大多数外源性化合物代谢解毒,但也与某些药物的毒性作用以及化学致癌有关。现已证明,肝内有多种形式的P-450,分别为不同的诱导剂所诱导。它们在光谱特性、底物特异性以及催化反应等方面有明显的区别,并证明酶的诱导是由特定基因调节的。此外,近年来多种P-450的分离分析方法也有了一定的提高。     

细胞色素P450与肿瘤

本文综棕了细胞色素Ｐ４５０同工酶与致癌物代谢、与抗癌药的相互作用以及化的关系,并对调控Ｐ４５０同工酶以防治肿瘤的策略进行了论述。由于Ｐ４５０同工酶具有多态性、工物特异性及可诱导性的特点,在调控Ｐ４５０同工酶以防治肿瘤的问题上,针对不同人群、不同疾病状况及不同用药方案可能需采取抑制或诱导的不同策略。     

What makes us human?

The sequence of chimpanzee chromosome 22 is starting to help us to define the set of genetic attributes that are unique to humans, but interpreting the biological consequences of these remains a major challenge.     

Meta-operation conflict resolution for human–human interaction in collaborative feature-based CAD systems

Conflicts resolution is one of the key issues in maintaining consistency and in supporting smooth human–human interaction for real-time collaborative systems. This paper presents a novel approach of meta-operation conflict resolution for feature-based collaborative CAD system. Although commutative replicated data type (CRDT) is an emerging technique for conflict resolution, it is not capable of resolving conflicts among meta operations for 3D CAD systems. By defining 3 types of meta operations, this work extends CRDT capability to meta operation conflict resolution from 1D to 3D applications. The paper defines the dependency, casuality, conflict and compatible relations specific for 3D collaborative CAD systems. The conflicts of feature-based operations are automatically detected by tracking topological entity changes with the assistance of a persistent data structure, topological entity structure tree (\(TES\_Tree\)). An efficient commutativity-based confliction combination method is proposed to preserve the design intention of each user in a transparent way and maintains the eventual consistent state of the system. The proposed methods are tested in a prototype system with case studies, time complexity analysis and correctness proof.     

Glycopeptides from human κ-chains

Glycopeptides have been isolated from tryptic digests of kappa-type light chains separated from human myeloma proteins obtained from the serum of two patients, Car and Rai. The glycopeptides are derived from the variable region of the chain in both cases, but from different sections. On the basis of homology it is deduced that glycopeptide from Car, kappaI type, is derived from position 25-31 whereas that from Rai, kappaII type, is from position 62-77, their sequences being respectively Ala-Ser-Gln-Asn-Ile-Ser and Phe-Ser-Gly-Ser-Gly-Ser-Gly(Thr,Asp)Phe-Thr-Leu-Asx-Ile-Ser-Arg. The significance of the results is discussed in connexion with the nature of the attachment site of carbohydrate to protein.