生物体砷代谢及其相关酶与蛋白的研究概况

砷在自然界分布广泛,主要以砷化物的形式存在,具有较强毒性。可通过多种途径进入人类的生活环境引起健康危害,砷代谢过程涉及到复杂的酶促或非酶促反应过程,近年来以砷代谢为突破口的砷中毒发病机制探索成为新的研究热点,本文就有关砷在生物体内代谢方面的研究做一综述,以期有助于慢性砷中毒作用机制的研究。     

饥荒造成的营养不良对成年后患代谢综合征的影响

研究生命早期因食物短缺造成的营养不良对成年后患代谢综合征（Metabolic syndrome,MS）的影响．探讨成年人慢性病的起因．为制订妇女儿童营养改善政策提供科学依据．对2005—2008年上半年重庆医科大学附属第一医院体检中心体检资料进行整群抽样．选出14917例样本．将三年自然灾害（1959～1961年）出生的研究对象3650例（G2组）作为受灾害影响人群,将灾害之前（1955～1957年）出生的4497例体检人群（G1组）和灾害之后（1963～1965年）6770例体检人群作为未受灾害影响人群（G3组）,比较3组人群体质指数、血糖值、血压值及血脂值4项MS各分项判断指标．运用SAS9．1分析MS发生情况．G1组检出MS463例,占G1组总人数的10．30％：G2组检出MS403例,占G2组总人数的11．04％：G3组检出MS609侧．占G3组总人数的9．00％．组间比较有统计学意义．男性检出MS1326例．患病率为14．06％．女性检出MS149例,患病率为2．72％．饥荒造成的机体早期营养不良与成年后患MS有关,对MS影响严重程度依次为血脂紊乱〉体质指数超标〉血压超标〉血糖超标．且男性比女性受影响显著,差异有统计学意义．故在选择孕妇、乳母以及婴幼儿饮食上,科学的供给和合理的配比显得尤为重要．可以借以提高整体人群的生存质量．     

代谢酶的非经典功能及代谢感知

代谢是基本的生命活动,代谢网络以代谢酶和代谢物为中心,为细胞的生命活动提供物质和能量基础。一方面,代谢酶发挥经典的功能,催化不同代谢通路中的代谢物,并受到严密调控,维持代谢稳态。另一方面,近年来国内外的研究,包括我们研究团队的工作证实了某些代谢酶和代谢物还可发挥非经典的兼有功能(moonlighting functions),参与信号通路调控和/或作为一个信号分子,对代谢进行更精细的调控,在机体的生理和病理过程中发挥关键作用。     

生命活动中信息传递的形态

阐述了生命活动过程中信息传递的形态,强调了信息传递与生命活动的关系,说明了生命活动是以一定的信息传递形态方式进行的。     

自噬与代谢及代谢性疾病

细胞自噬是真核生物中一种高度保守的代谢过程,可以清除受损的细胞器,降解糖原、脂类、蛋白质等生物大分子物质供细胞重新利用,对维持细胞内代谢平衡有重要意义。自噬障碍常被发现与代谢性疾病相关,如酸性麦芽糖酶缺乏症、肥胖和神经退行性疾病等。该文就近年来关于自噬与代谢及代谢性疾病的研究作一综述。     

基于真实情境的"人体代谢废物的排出"的专题复习

以"人体代谢废物的排出"的专题复习为例,创设"肾脏疾病患者的诊断和治疗及肾病预防方法"这一真实情境,培养学生应用知识解决实际问题的能力.同时,借助病理学中肾脏的异常结构,培养学生的生命观念和科学思维.     

基于代谢流量分布信息理解大肠杆菌中异柠檬酸裂解酶调节因子的代谢调控作用

基因的表达受不同的转录调节因子调节。大肠杆菌中的异柠檬酸裂解酶调节因子(IclR)能够抑制编码乙醛酸支路酶的aceBAK操纵子的表达。本研究基于代谢物的13C同位体物质分布来定量解析代谢反应,主要研究了iclR基因在大肠杆菌生理和代谢中的作用。大肠杆菌iclR基因缺失突变株的生长速率、糖耗速率和乙酸的产量相对于原始菌株都有所降低,但菌体得率略有增加。通过代谢途径的流量比率分析发现基因缺失株的乙醛酸支路得到了激活,33%的异柠檬酸流经了乙醛酸支路;戊糖磷酸途径的流量变小,使得CO2的生成量减少。同时,乙醛酸支路激活,但草酰乙酸形成磷酸烯醇式丙酮酸的流量基本不变,说明磷酸烯醇式丙酮酸-乙醛酸循环没有激活,没有过多的碳原子在磷酸烯醇式丙酮酸羧化激酶反应中以CO2形式排出,从而确保了菌体得率。葡萄糖利用速率的降低、乙酰辅酶A的代谢效率提高等使得iclR基因敲除菌的乙酸分泌较原始菌株有所降低。     

槲皮素代谢的研究进展

槲皮素（quercetin)及其衍生物是膳食成分中最常见的类黄酮物质之一,也是一些中草药的有效成分,具有清除自由基,抑制炎症反应,抗癌防癌等多种生物活性,日益成为国内外研究的热点,本文综述了近几年国外有关槲皮素及其衍生物代谢方面的研究,包括其吸收形式,吸收部位和吸收机制,以及在体内各器官的转化,运输和排泄等。     

一张适用于总结物质代谢途径的代谢联络图

介绍了一张适用于总结物质代谢途径之间相互联系的代谢联络图。通过此图可让学生对营养物质代谢、能量代谢及其彼此之间的联系有一个整体的认识,还可显现出各条代谢途径间的枢纽性物质,以总结归纳这些物质的来源和去路,并在分子水平上阐明与代谢有关的某些疾病的原因。     

代谢调衡饮对代谢综合征胰岛素抵抗的影响

目的:初步探讨代谢调衡饮对代谢综合征胰岛素抵抗的影响。方法:将60例代谢综合征患者随机分为试验组和对照组,对照组口服卡托普利和二甲双胍,试验组在此基础上加服代谢调衡饮,疗程3个月。结果:两组各个时间点的血糖和HbA1c与治疗前相比,均有显著下降(P<0.01);显著降低空腹、糖负荷后0.5h、1h、2h、3h胰岛素水平(P<0.01),与对照组相比,试验组降低糖负荷后0.5h胰岛素水平更具优势(P<0.01);明显降低HOMA-IR,升高ISI。结论:代谢调衡饮对于改善代谢综合征患者的胰岛素抵抗具有一定疗效。     

On the observable transition to living matter

In recent developments in chemistry and genetic engineering, the humble researcher dealing with the origin of life finds her(him)self in a grey area of tackling something that even does not yet have a clear definition agreed upon. A series of chemical steps is described to be considered as the life-nonlife transition, if one adheres to the minimalistic definition: life is self-reproduction with variations. The fully artificial RNA system chosen for the exploration corresponds sequence-wise to the reconstructed initial triplet repeats, presumably corresponding to the earliest protein-coding molecules. The demonstrated occurrence of the mismatches (variations) in otherwise complementary syntheses ("self-reproduction"), in this RNA system, opens an experimental and conceptual perspective to explore the origin of life (and its definition), on the apparent edge of the origin.     

Applications of a parametric model for informative censoring

In this article, we explore the use of a parametric model (for analyzing survival data) which is defined to allow sensitivity analysis for the presence of informative censoring. The dependence between the failure and the censoring processes is expressed through a parameter delta and a general bias function B(t, theta). We calculate the expectation of the potential bias due to informative censoring, which is an overall measure of how misleading our results might be if censoring is actually nonignorable. Bounds are also calculated for quantities of interest, e.g., parameter of the distribution of the failure process, which do not depend on the choice of the bias function for fixed delta. An application that relates to systematic lupus erythematosus data illustrates how additional information can result in reducing the uncertainty on estimates of the location parameter. Sensitivity analysis on a relative risk parameter is also explored.     

From prebiotic chemistry to cellular metabolism--the chemical evolution of metabolism before Darwinian natural selection

It is generally assumed that the complex map of metabolism is a result of natural selection working at the molecular level. However, natural selection can only work on entities that have three basic features: information, metabolism and membrane. Metabolism must include the capability of producing all cellular structures, as well as energy (ATP), from external sources; information must be established on a material that allows its perpetuity, in order to safeguard the goals achieved; and membranes must be able to preserve the internal material, determining a selective exchange with external material in order to ensure that both metabolism and information can be individualized. It is not difficult to understand that protocellular entities that boast these three qualities can evolve through natural selection. The problem is rather to explain the origin of such features under conditions where natural selection could not work. In the present work we propose that these protocells could be built by chemical evolution, starting from the prebiotic primordial soup, by means of chemical selection. This consists of selective increases of the rates of certain specific reactions because of the kinetic or thermodynamic features of the process, such as stoichiometric catalysis or autocatalysis, cooperativity and others, thereby promoting their prevalence among the whole set of chemical possibilities. Our results show that all chemical processes necessary for yielding the basic materials that natural selection needs to work may be achieved through chemical selection, thus suggesting a way for life to begin.     

Direct measurement of oxidative metabolism in the living brain by microdialysis: a review

This review summarizes microdialysis studies that address the question of which compounds serve as energy sources in the brain. Microdialysis was used to introduce ¹⁴C-labeled glucose, lactate, pyruvate, glutamate, glutamine, and acetate into the interstitial fluid of the brain to observe their metabolism to ¹⁴CO₂. Although glucose uptake from the systemic system supplies the carbon source for these compounds, compounds synthesized from glucose by the brain are subject to recycling including complete metabolism to CO₂. Therefore, the brain utilizes multiple compounds in its domain to provide the energy needed to fulfill its function. The physiological conditions controlling metabolism and the contribution of compartmentation into different brain regions, cell types, and subcellular spaces are still unresolved. The aconitase inhibitor fluorocitrate, with a lower inhibition threshold in glial cells, was used to identify the proportion of lactate and glucose that was oxidized in glial cells versus neurons. The fluorocitrate data suggest that glial and neuronal cells are capable of utilizing both lactate and glucose for energy metabolism.     

Flexible hazard regression modeling for medical cost data

The modeling of lifetime (i.e. cumulative) medical cost data in the presence of censored follow-up is complicated by induced informative censoring, rendering standard survival analysis tools invalid. With few exceptions, recently proposed nonparametric estimators for such data do not extend easily to handle covariate information. We propose to model the hazard function for lifetime cost endpoints using an adaptation of the HARE methodology (Kooperberg, Stone, and Truong, Journal of the American Statistical Association, 1995, 90, 78-94). Linear splines and their tensor products are used to adaptively build a model that incorporates covariates and covariate-by-cost interactions without restrictive parametric assumptions. The informative censoring problem is handled using inverse probability of censoring weighted estimating equations. The proposed method is illustrated using simulation and also with data on the cost of dialysis for patients with end-stage renal disease.     

On invariant property in population statistics

Concept of aging is developed to yield a relationship between life spans and the velocity of aging. The mathematical analysis shows that the mean extent of the advancement of aging throughout one’s life is conserved, or equivalently, the product of the mean life span, T, and the mean rate of aging, , is constant, . The result is in harmony with our experiences: it accounts for the unlimited replicability of tumor cells, and predicts the prolonged life spans of hibernating hamsters according to the equation, (T_χ=0 is a constant and χ denotes the total fraction of hibernation periods), in accordance with the Lyman and co-workers experiment. Comparing the present result and the empirical relationship between life spans of various mammals and basal metabolic rates, it is suggested that the mean rate of aging is intimately connected with the mean basal metabolic rate. With the help of this information, we inquire the reason of the difference in mean life spans between women and men, the result showing that the relative mean life span of women to men is T_women/T_men ≅ 1.08 for various nations, which is close to the corresponding relative value of the basal metabolic rate. The present analysis suggests, however, that this relationship between life spans and basal metabolic rates must be treated with caution.     

The effect of ethanol on zinc and copper metabolism in rats

Studies performed on adult female rats over a period of 10 weeks indicated that the consumption of alcohol (20% v/v) did not appear to disturb the zinc or copper balance, nor did it adversely affect tissue zinc or copper levels, even in zinc-restricted animals. On the contrary, higher plasma zinc levels were consistently observed in animals receiving alcohol together with the experimental diets.     

Predicting metabolic biomarkers of human inborn errors of metabolism

Early diagnosis of inborn errors of metabolism is commonly performed through biofluid metabolomics, which detects specific metabolic biomarkers whose concentration is altered due to genomic mutations. The identification of new biomarkers is of major importance to biomedical research and is usually performed through data mining of metabolomic data. After the recent publication of the genome‐scale network model of human metabolism, we present a novel computational approach for systematically predicting metabolic biomarkers in stochiometric metabolic models. Applying the method to predict biomarkers for disruptions of red‐blood cell metabolism demonstrates a marked correlation with altered metabolic concentrations inferred through kinetic model simulations. Applying the method to the genome‐scale human model reveals a set of 233 metabolites whose concentration is predicted to be either elevated or reduced as a result of 176 possible dysfunctional enzymes. The method's predictions are shown to significantly correlate with known disease biomarkers and to predict many novel potential biomarkers. Using this method to prioritize metabolite measurement experiments to identify new biomarkers can provide an order of a 10‐fold increase in biomarker detection performance.     

On the Origin of Metabolic Pathways

The heterotrophic theory of the origin of life is the only proposal available with experimental support. This comes from the ease of prebiotic synthesis under strongly reducing conditions. The prebiotic synthesis of organic compounds by reduction of CO₂ to monomers used by the first organisms would also be considered an heterotrophic origin. Autotrophy means that the first organisms biosynthesized their cell constituents as well as assembling them. Prebiotic synthetic pathways are all different from the biosynthetic pathways of the last common ancestor (LCA). The steps leading to the origin of the metabolic pathways are closer to prebiotic chemistry than to those in the LCA. There may have been different biosynthetic routes between the prebiotic and the LCAs that played an early role in metabolism but have disappeared from extant organisms. The semienzymatic theory of the origin of metabolism proposed here is similar to the Horowitz hypothesis but includes the use of compounds leaking from preexisting pathways as well as prebiotic compounds from the environment.