Genetic metabolic polymorphisms and the risk of cancer: a review of the literature

The purpose of this paper is to systematically analyse the design and results of epidemiological studies on the association between various types of cancer (lung, bladder, breast, colon, stomach) and four genetically-based metabolic polymorphisms, involved in the metabolism of several carcinogens (glutathione-S-transferase M1, debrisoquine hydroxylase, N acetyltransferase, aryl hydrocarbon hydroxylase). These inherited polymorphisms usually cause modifications in the quality or quantity of the relevant enzymes. Such enzymes are involved in the activation/inactivation of known carcinogens and seem to modify the extent to which carcinogens interact with DNA in target tissues. Two enzymes, debrisoquine hydroxylase and aryl hydrocarbon hydroxylase, activate procarcinogens to carcinogens (phase I enzymes). The other two, glutathione-S-transferase M1 and N-acetyltransferase, mainly detoxity carcinogenic substances (phase II enzymes). Because of their role as host factors (modulating the action of carcinogens), it has been hypothesized that subjects presenting a specific phenotype for such polymorphisms could be at a greater risk of developing various types of cancer. A number of epidemiological studies have investigated such associations, often with discordant results. We examine and discuss the design of the studies, and present a meta-analysis of the available data.     

CaM BP－10对NAD激酶的抑制效应

ＮＡＤ激酶在光合作用等植物生理过程中起重要作用。ＮＡＤ激酶的激活依赖于钙离子和钙调素（ＣａｌｍＯｄｕｌｉｎ,ＣａＭ）．从植物中分离得到的一种新的ＣａＭ结合蛋白ＣａＭＢＰ－１０（ＢＰ－１０）明显抑制ＮＡＤ激酶的激活活性,抑制作用可被ＣａＭ所克服．动力学研究表明,抑制效应是ＢＰ－１０与ＣａＭ之间特异性相互作用的结果。实验证实ＢＰ－１０对ＮＡＤ激酶活性起着重要调节作用．     

Two Phenol Sulfotransferase Species from One cDNA: Nature of the Differences

A phenol sulfotransferase from rat liver (EC 2.8.2.9), expressed inEscherichia colifrom a single cDNA, was purified as two separable but catalytically active proteins. The proteins appeared to be identical to each other and to the natural liver sulfotransferase by comparison of their amino acid constitution, amino-terminal end group, and interaction with a polyclonal antibody raised against the liver enzyme. Each of the recombinant forms, α and β, catalyzed the sulfuryl group transfer from 4-nitrophenylsulfate to an acceptor phenol, a reaction in which 3′-phospho-adenosine 5′-phosphate (PAP) is a necessary intermediate. Only form β, however, catalyzes the physiological transfer of a sulfuryl group from 3′-phosphoadenosine 5′-phosphosulfate (PAPS) to the free phenol. Evidence is presented that sulfotransferase α, but not β, has 1 mol of PAP tightly bound per enzyme dimer. The ability to utilize PAPS as a sulfate donor could be altered: form α could be treated and purified as form β to acquire the ability to use PAPS, whereas form β was treated by extended incubation with PAP, lost its ability to use PAPS, and was purified as form α.     

Phospholipid surface density determines the partitioning and permeability of acetic acid in DMPC:cholesterol bilayers

Relationships between the permeability coefficient (P_HA) and partition coefficient (K _m/w) of acetic acid and the surface density of DMPC:cholesterol bilayers have been investigated. Permeability coefficients were measured in large unilamellar vesicles by NMR line broadening. Bilayer surface density, , was varied over a range of 0.5–0.9 by changing cholesterol concentration and temperature. The temperature dependence of P_HA for acetic acid exhibits Arrhenius behavior with an average apparent activation energy (E _a ) of 22±3 kcal/mole over a cholesterol mole fraction range of 0.00–0.40. This value is much greater than the enthalpy change for acetic acid partitioning between bulk decane and water (H° = 4.8±0.8 kcal/mole) and the calculated E _a (= 8.0 kcal/mole) assuming a bulk phase permeability model which includes the enthalpy of transfer from water to decane and the temperature dependence of acetic acid's diffusion coefficient in decane. These results suggest that dehydration, previously considered to be a dominant component, is a minor factor in determining E _a . Values of 1n P_HA decrease linearly with the normalized phospholipid surface density with a slope of = -12.4±1.1 (r = 0.90). Correction of P_HA for those temperature effects considered to be independent of lipid chain order (i.e., enthalpy of transfer from water to decane and activation energy for diffusion in bulk hydrocarbon) yielded an improved correlation ( = -11.7±0.5 (r = 0.96)). The temperature dependence of K_m/w is substantially smaller than that for P_HA and dependent on cholesterol composition. Values of 1n K_m/w decrease linearly with the surface density with a slope of = -4.6±0.3 (r = 0.95), which is 2.7-fold smaller than the slope of the plot of 1n P_HA vs. . Thus, chain ordering is a major determinant for molecular partitioning into and transport across lipid bilayers, regardless of whether it is varied by lipid composition or temperature.This work was supported by grants from Glaxo, INTERx/Merck, and University of Utah Research Committee.     

薏苡胚乳传递细胞的超微结构

传粉后１０ ｄ,薏苡（Ｃｏｉｘ ｌａｃｒｙｍ ａ－ｊｏｂｉＬ．）颖果基部胚乳最外层传递细胞具长而多的壁内突,第二层细胞的壁内突较第一层的短而少,均具瓣裂的细胞核、丰富的线粒体、粗糙内质网、核糖体、产生小泡的高尔基体及与壁内突质膜相连的、含深色物质的囊泡。线粒体分布于壁内突附近或其间。授粉后２５ ｄ,第一、二层细胞壁内突发达,几乎充满了细胞,但细胞器可见。第四层传递细胞具树枝状及网状的壁内突,大量线粒体、具质体膜的淀粉粒、脂体存在壁内突附近或壁内突的间隙内。高尔基体常见,仅见很少的片段内质网。第五层传递细胞具短的壁内突、较大的淀粉粒及许多小蛋白质体。两个时期的第一、二层细胞内均未观察到胞间连丝。授粉后２５ ｄ,第四层及以上的传递细胞的细胞壁和呈网状的壁内突均含有胞间连丝。还讨论了各种细胞器的作用及各层传递细胞的功能     

Three-dimensional structure prediction of the NAD binding site of proton-pumping transhydrogenase from Escherichia coli

A three-dimensional structure of the NAD site of Escerichia coli transhydrogenase has been predicted. The model is based on analysis of conserved residues among the transhydrogenases from five different sources, homologies with enzymes using NAD as cofactors or substrates, hydrophilicity profiles, and secondary structure predictions. The present model supports the hypothesis that there is one binding site, located relatively close to the N-terminus of the α-subunit. The proposed structure spans residues α145 to α287, and it includes five β-strands and five α-helices oriented in a typical open twisted α/β conformation. The amino acid sequence following the GXGXXG dinucleotide binding consensus sequence (residues α172 to α177) correlates exactly to a typical fingerprint region for ADP binding βαβ folds in dinucleotide binding enzymes. In the model, aspartic acid α195 forms hydrogen bonds to one or both hydroxyl groups on the adenosine ribose sugar moiety. Threonine α196 and alanine α256, located at the end of βB and βD, respectively, create a hydrophobic sandwich with the adenine part of NAD buried inside. The nicotinamide part is located in a hydrophobic cleft between αA and βE. Mutagenesis work has been carried out in order to test the predicted model and to determine whether residues within this domain are important for proton pumping directly. All data support the predicted structure, and no residue crucial for proton pumping Was detected. Since no three-dimensional structure of transhydrogenase has been solved, a well based tertiary structure prediction is of great value for further experimental design in trying to elucidate the mechanism of the energy-linked proton pump. © 1995 Wiley-Liss, Inc.     

Nuclear migration advances in fungi

Nuclear migration encompasses three areas: separation of daughter nuclei during mitosis, congress of parental nuclei before they fuse during fertilization, and positioning of nuclei in interphase cells. This review deals primarily with interphase nuclear migration, which is crucial for events as disparate as vertebrate embryonic development and growth of fungal mycelia. Mutants of Aspergillus nidulans, Neurospora crassa and Saccharomyces cerevisiae have been particularly informative, and a detailed molecular analysis of this process is now well under way.     

钙调神经磷酸酶在胍变性过程中活力及构象变化的比较

钙调神经磷酸酶（ＣａＮ）在盐酸胍溶液中的内源荧光、远紫外ＣＤ谱及剩余活力的变化提示：ＣａＮ的酶活力在胍浓度为０．５ｍｏｌ／Ｌ左右可完全丧失,同时伴有内源荧光强度的下降,３３３ｎｍ最大发射峰的红移（提示了色氨酸和酪氨酸残基的暴露）。比较不同胍浓度下牛脑ＣａＮ的失活与整体构象变化,表明酶的失活先于整体构象变化。在０．６ｍｏｌ／Ｌ胍溶液中,内源荧光变化的动力学过程只能测出一相,而酶失活的动力学过程为快、慢两相,快相动力学速度常数比整体构象变化速度常数大１－２个数量级,慢相失活速度常数与整体构象变化速度常数相近。提示低浓度胍可引起该酶的完全失活,活性部位的空间构象比整个酶分子的构象更易受到变性剂的扰乱。     

药用野生稻GBSS基因的系统发育及组织特异性表达

淀粉作为主要的碳水化合物在储藏能量方面发挥至关重要的作用。颗粒结合型淀粉合酶(GBSS)与直链淀粉的合成息息相关。尽管该酶的编码基因已在许多栽培植物中被分离和确定, 但有关它们在作物野生近缘种中的序列分歧和表达的研究却相对较少。该研究以药用野生稻(Oryza officinalis)为研究对象, 定性和定量地分析了GBSS编码基因的序列特点、与其它植物同源基因的进化关系以及在叶和种子中的表达情况。系统发育分析表明, 该酶在禾本科植物中分别由GBSSI和GBSSII基因编码。在药用野生稻中, 这2种基因所编码蛋白的氨基酸序列一致性为62%, 并且它们在不同器官内呈现时空分化表达, 其中GBSSI在种子中超强表达, GBSSII则主要在叶片表达。