高等植物中一碳化合物代谢研究进展

高等植物中一碳(C1)化合物的代谢主要包括甲醇代谢、甲醛代谢和甲酸代谢等,它们是高等植物一碳单位代谢的重要组成部分.由于C1化合物的代谢机制复杂、代谢规模非常小、参与代谢反应的酶和中间产物的含量低且不稳定等特点,相关研究报道很有限.现代生化和分子遗传学方法的综合使用使得人们对参与植物中C1化合物代谢的酶和基因有了一定程度的了解,该文主要综述了近年来有关高等植物中内源和外源C1化合物甲醇、甲醛和甲酸的来源和代谢途径方面的研究进展,并提出了该研究领域目前存在的问题和今后的研究方向.     

Upstream regulators of apoptosis mediates methionine-induced changes of lipid metabolism

Although the role of methionine (Met), as precursor for l-carnitine synthesis, in the regulation of lipid metabolism has been explored. Met seems to have tissue- and species-specific regulatory effect on lipid metabolism, implying that the mechanisms in Met regulation of lipid metabolism is complex and may involve the upstream regulatory pathway of lipid metabolism. The present study was performed to determine the mechanism of apoptosis signaling pathways mediating Met-induced changes of hepatic lipid deposition and metabolism in fish, and compare the differences of the mechanisms between the fish and mammals. By iTRAQ-based quantitative proteome analyses, we found that both dietary Met deficiency and excess evoked apoptosis signaling pathways, increased hepatic lipid deposition and caused aberrant hepatic lipid metabolism of yellow catfish Pelteobagrus fulvidraco. Using primary hepatocytes from P. fulvidraco, inhibition of caspase by Z-VAD-FMK blocked the apoptotic signaling pathways with a concomitant reversal of Met deficiency- and excess-induced increase of lipid deposition, indicating that apoptosis involved the Met-mediated changes of hepatic lipid metabolism. Moreover, we explored the roles of three upstream apoptotic signaling pathways (PI3K/AKT-TOR pathway, cAMP/PKA/CREB pathway and LKB1/AMPK-FOXO pathway) influencing hepatic lipid metabolism of P. fulvidraco. The three upstream pathways participated in apoptosis mediating Met-induced changes of lipid metabolism in P. fulvidraco. At last, HepG2 cell line was used to compare the similarities of mechanisms in apoptosis mediating Met-induced changes of lipid metabolism between fish and mammals. Although several slight differences existed, apoptosis mediated the Met-induced changes of lipid metabolism between fish and mammals. The present study reveals novel apoptosis-relevant signal transduction axis which mediates the Met-induced changes of lipid metabolism, which will help understand the mechanistic link between apoptosis and lipid metabolism, and highlight the importance of the evolutionary conservative apoptosis signaling axis in regulating Met–induced changes of hepatic lipid metabolism.     

Regulation of rat and bovine adrenal metabolism of polycyclic aromatic hydrocarbons by adrenocorticotropin and 2,3,7,8-tetrachlorodibenzo-p-dioxin

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on polycyclic aromatic hydrocarbon (PAH) metabolism and steroidogenesis in primary cultures of bovine adrenal cortical (BAC) and rat adrenal cortical (RAC) cells have been examined. Remarkably TCDD is an ineffective inducer (15-50%) of PAH metabolism in confluent BAC cells and completely antagonizes a 5-fold induction by benz[alpha]anthracene (BA). In the same concentration range (EC50 5 X 10(-11) M) TCDD suppresses steroidogenesis through an effect on cholesterol metabolism. Adrenocorticotropin (ACTH) and cAMP also suppress PAH metabolism at concentrations which stimulate steroidogenesis (10(-7) M). In RAC cells ACTH potently induces PAH metabolism (7-fold) at a comparable concentration to the stimulation of steroidogenesis. Parallel stimulation of PAH metabolism and steroidogenesis by cAMP suggest that ACTH induction of PAH metabolism is mediated by cAMP. TCDD induces PAH metabolism (2.8-fold, EC50 8 X 10(-11) M) at similar concentrations to the inhibitory effect in BAC cells and this action is additive with ACTH induction. In male rats in vivo TCDD induces adrenal microsomal PAH metabolism (72%) and is more effective in this respect than 3-methylcholanthrene (3MC). Rabbit antibodies against rat liver cytochrome P-450c (the major TCDD-inducible liver form) inhibited the TCDD-induced adrenal metabolism of 7,12-dimethylbenz[alpha]anthracene (DMBA), which also exhibited regioselectivity typical of metabolism by P-450c. Constitutive adrenal microsomal metabolism, which exhibited regioselectivity of DMBA metabolism comparable to the ACTH-sensitive cellular metabolism, was not affected by anti-P-450c. It is concluded that ACTH and TCDD induce distinct forms of cytochrome P-450 in RAC cells and that the latter represents a typical Ah-receptor mediated response. The anomalous effect on PAH metabolism in BAC cells that parallels inhibition of steroidogenesis may derive from repression of a distinct adrenal form of P-450 by the TCDD-Ah-receptor complex.     

The state of dog's metabolism after long interval after oxide tritium administration

An attempt to evaluate the influence of tritium oxide on the metabolism by some indices of lipid metabolism (common lipids, beta-lipoproteins, cholesterin), protein metabolism (cholinesterasa) and carbohydrate metabolism (blood sugar) was made. It was established that the introduction into organism of tritium oxide in the quantities, which could form lethal and sublethal doses of internal radiation, provoked the main changes of values of mentioned indices of metabolism. The character of metabolism changes in the remote period allows us to judge about the development of sclerosis processes, which can be the result of radiation-stipulated acceleration of organism aging.     

莱茵衣藻中脂质代谢过程研究进展

微藻中脂质代谢产生的化合物,可用于生物燃料、营养品和生物药品的生产,因此具有重要的经济价值。脂质代谢贯穿微藻的全部生命过程,对微藻的生长发育和应对外界胁迫都具有重要意义。微藻与研究较清楚的真菌和陆地植物在脂质代谢过程方面具有相似性。当然,随着微藻脂质代谢相关功能基因逐渐被鉴定,人们发现微藻的脂质代谢也具有区别真菌和陆地植物的独特性,因此针对微藻脂质代谢过程的分析具有重要意义。莱茵衣藻是研究脂质代谢过程的模式生物,已经通过基因组、转录组、蛋白质组和代谢组等方法,对其质体、内质网和过氧化物酶体中进行的脂质合成和分解过程进行了研究。本文总结了近年来莱茵衣藻质体、内质网和过氧化物酶体中脂质代谢过程的研究成果,并进行综合阐述。     

The Biochemistry of Drug Metabolism – An Introduction

This review is part of a series of review articles on the metabolism of drugs and other xenobiotics published in Chemistry & Biodiversity. After a thorough discussion of metabolic reactions and their enzymes, this article focuses on genetically determined differences in drug and xenobiotic metabolism. After a short introduction on the causes for genetic differences, the first focus is on species differences in drug and xenobiotic metabolism. A major chapter is then dedicated to clinically relevant genetic polymorphisms in human drug metabolism and resultant ethnic differences. The last two chapters deal with sex‐dependent differences in drug metabolism and personalized pharmacotherapy related to inter‐individual differences in drug metabolism.     

Eco-efficiency of urban material metabolism: a case study in Shenzhen, China

The keys of studying urban sustainable development are material metabolism flux and efficiency. Metabolism flux of urban materials can only reflect the metabolism velocity, while its eco-efficiency can determine the metabolism capacity to support socio-economic development. The general model and the measure model of the eco-efficiency were set up, based on the source recycle (decreasing the consumption of crude resources) and the terminal recycle (decreasing the discharge of pollutants) of production and life. These models were employed to study material metabolism flux and efficiency in Shenzhen, China. Results showed that water, energy and waste metabolism fluxes have increased since 1998 with constant socio-economic development, and their eco-efficiencies have also increased rapidly. When GDP rose by 2.7 times, the metabolism fluxes of urban water and electricity rose by 1.5 and 3.0 times, respectively. When the added value of industry rose by 3.7 times, the metabolism fluxes of industrial water, electricity, energy and waste rose by 1.9, 3.5, 2.7 and 2.0 times, respectively. When population rose by 1.5 times, the metabolism fluxes of residential water and electricity rose by 1.8 and 1.7 times, respectively. During the period, the resource efficiency, environmental efficiency and eco-efficiency rose by 1.8, 3.7 and 2.3 times, respectively. Whereas the efficiency of material metabolism has been improved in Shenzhen, the scarcity of material resources has become more and more serious. Therefore, it is necessary to further improve the efficiency of material metabolism. The keys of improving the eco-efficiency of urban material metabolism are the increasing of resource and environmental efficiencies, and the establishing of the recycling chain of re-utilization of waste resources.     

Eco-efficiency of urban material metabolism: a case study in Shenzhen, China

The keys of studying urban sustainable development are material metabolism flux and efficiency. Metabolism flux of urban materials can only reflect the metabolism velocity, while its eco-efficiency can determine the metabolism capacity to support socio-economic development. The general model and the measure model of the eco-efficiency were set up, based on the source recycle (decreasing the consumption of crude resources) and the terminal recycle (decreasing the discharge of pollutants) of production and life. These models were employed to study material metabolism flux and efficiency in Shenzhen, China. Results showed that water, energy and waste metabolism fluxes have increased since 1998 with constant socio-economic development, and their eco-efficiencies have also increased rapidly. When GDP rose by 2.7 times, the metabolism fluxes of urban water and electricity rose by 1.5 and 3.0 times, respectively. When the added value of industry rose by 3.7 times, the metabolism fluxes of industrial water, electricity, energy and waste rose by 1.9, 3.5, 2.7 and 2.0 times, respectively. When population rose by 1.5 times, the metabolism fluxes of residential water and electricity rose by 1.8 and 1.7 times, respectively. During the period, the resource efficiency, environmental efficiency and eco-efficiency rose by 1.8, 3.7 and 2.3 times, respectively. Whereas the efficiency of material metabolism has been improved in Shenzhen, the scarcity of material resources has become more and more serious. Therefore, it is necessary to further improve the efficiency of material metabolism. The keys of improving the eco-efficiency of urban material metabolism are the increasing of resource and environmental efficiencies, and the establishing of the recycling chain of re-utilization of waste resources.     

脑铁代谢及调控

随着研究的深入,脑铁代谢相关分子突变引起的疾病越来越多的被人们所认识。脑铁代谢紊乱可能是神经退行性疾病的发病原因之一。对脑铁代谢机理的认识将为预防和治疗脑铁代谢紊乱相关疾病提供重要的理论根据。对脑铁代谢的过程,脑铁代谢的相关分子以及这些分子对脑内铁稳态的调控作用作一介绍。     

Metabonomic studies on potential plasma biomarkers in rats exposed to ionizing radiation and the protective effects of Hong Shan Capsule

An ultra performance liquid chromatography coupled to mass spectrometry-based metabonomic approach, combined with pattern recognition methods including PCA, PLS-DA, RF and heatmap, has been developed to characterize the global serum metabolic profile associated with ionizing radiation (IR). As the VIP-value threshold cutoff of the metabolites was set to 2, metabolites above this threshold were filtered out as potential target biomarkers. Nineteen distinct potential biomarkers in rat plasma were identified. To further elucidate the pathophysiology of IR, related metabolic pathways have been studied. It was found that IR was closely related to disturbed fatty acid metabolism, taurine and hypotaurine metabolism, sphingolipid metabolism, purine metabolism, pyrimidine metabolism, phospholipid catabolism, tryptophan metabolism, phenylalanine metabolism, and bile acid metabolism. With the presented metabonomic method, we systematically analyzed the protective effects of Traditional Chinese Medicine Hong Shan Capsule (HSC). The results demonstrated that HSC administration could provide satisfactory effects on IR through partially regulating the perturbed metabolic pathways.     

Down-regulated energy metabolism genes associated with mitochondria oxidative phosphorylation and fatty acid metabolism in viral cardiomyopathy mouse heart

The majority of experimental and clinical studies indicates that the hypertrophied and failing myocardium are characterized by changes in energy and substrate metabolism that attributed to failing heart changes at the genomic level, in fact, heart failure is caused by various diseases, their energy metabolism and substrate are in different genetic variations, then the potential significance of the molecular mechanisms for the aetiology of heart failure is necessary to be evaluated. Persistent viral infection (especially coxsackievirus group B3) of the myocardium in viral myocarditis and viral dilated cardiomyopathy has never been neglected by experts. This study aimed to explore the role and regulatory mechanism of the altered gene expression for energy metabolism involved in mitochondrial oxidative phosphorylation, fatty acid metabolism in viral dilated cardiomyopathy. cDNA Microarray technology was used to evaluate the expression of >35,852 genes in a mice model of viral dilated cardiomyopathy. In total 1385 highly different genes expression, we analyzed 33 altered genes expression for energy metabolism involved in mitochondrial oxidative phosphorylation, fatty acid metabolism and further selected real-time-PCR for quantity one of regulatory mechanisms for energy including fatty acid metabolism—the UCP2 and assayed cytochrome C oxidase activity by Spectrophotometer to explore mitochondrial oxidative phosphorylation function. We found obviously different expression of 33 energy metabolism genes associated with mitochondria oxidative phosphorylation, fatty acid metabolism in cardiomyopathy mouse heart, the regulatory gene for energy metabolism: UCP2 was down-regulated and cytochrome C oxidase activity was decreased. Genes involved in both fatty acid metabolism and mitochondrial oxidative phosphorylation were down-regulated, mitochondrial uncoupling proteins (UCP2) expression did not increase but decrease which might be a kind of adaptive protection response to regulate energy metabolism for ATP produce.     

The metabolism of U.S. cities 2.0

In the fifty years since Abel Wolman first published an estimate of U.S. urban metabolism, the field of urban metabolism has begun to thrive, with cities outside the United States being much of the focus. As cities attempt to meet local and international sustainability goals, it is time to revisit the metabolism of cities within the United States. Using existing empirical databases for material flows (the Freight Analysis Framework) and a published database on urban water flux, we provide a revised estimate of urban metabolism for the typical U.S. city. We estimate median values of metabolism for a city of one million people, considering water resources, food, fuel, and construction materials. Food consumption and waste production increased substantially to 3,800 metric tons per day and 4,900 metric tons per day, respectively. To facilitate a second generation of urban metabolism, we extend traditional analyses to include the embedded energy required to facilitate material consumption with important implications in determining sustainable urban metabolism. We estimate that a city of one million people requires nearly 4,000 gigajoules of primary energy per day to facilitate its metabolism. Our results show high heterogeneity of urban metabolism across the United States. As a result of the study, we conclude that there is a distinct need to promote policies at the regional or city scale that collect data for urban metabolism studies. Urban metabolism is an important educational and decision‐making tool that, with an increase in data availability, can provide important information for cities and their sustainability goals.     

α-核突触蛋白基因突变小鼠脑组织中内源性代谢产物的变化

目的:明确α-核突触蛋白与帕金森病的病理生理相关性及其临床意义。方法:采用相色谱-质谱联用(UPLC-MS)检测野生型小鼠和基因突变型小鼠脑组织中内源性代谢性产物,通过mzcloud法对小鼠脑组织中内源性代谢物质进行鉴定,将相应数据进行主成分分析(PCA)和聚类分析,分析其相关差异表达代谢物,并构建通路图和互作网络图。结果:(1)基于LC/MS法的代谢组分析结果显示两组间差异代谢物以氨基酸类及磷脂类等为主,包括β-丙氨酰-L-组氨酸、L-精氨酸、L-组氨酸、L-亮氨酸、L-苯丙氨酸、L-缬氨酸、L-天门冬氨酸、L-丙氨酸、磷脂酰胆碱等;(2)构建的代谢通路主要涉及酮体的合成和降解、牛磺酸和亚牛磺酸代谢、丙氨酸,天冬氨酸和谷氨酸代谢、精氨酸和脯氨酸代谢、组氨酸代谢、苯丙氨酸代谢、缬氨酸,亮氨酸和异亮氨酸的生物合成、甘油磷脂代谢等,从中发现18个具有标志性的代谢成分。结论:α-核突触蛋白基因突变后,酮体的合成和降解、牛磺酸和亚牛磺酸代谢、丙氨酸,天冬氨酸和谷氨酸代谢、精氨酸和脯氨酸代谢、组氨酸代谢、苯丙氨酸代谢、缬氨酸,亮氨酸和异亮氨酸的生物合成、甘油磷脂代谢等代谢通路发生了变化,涉及β-丙氨酰-L-组氨酸、L-精氨酸、L-组氨酸、L-亮氨酸、L-苯丙氨酸、L-缬氨酸、L-天门冬氨酸、L-丙氨酸、磷脂酰胆碱等的生物学标志性代谢产物变化。     

谷氨酰胺代谢与肿瘤

“谷氨酰胺代谢”是肿瘤细胞除Warburg效应外又一重要的能量代谢方式。迅速增殖的肿瘤细胞消耗谷氨酰胺（glutamine,Gin）来提供生长和增殖所需的能量和生物大分子原料,维持细胞内氧化还原稳态和参与细胞内信号通路的转导。肿瘤中原癌基因与抑癌基因的突变会影响Gin代谢。结合先进的诊断技术和研究手段将有利于了解肿瘤中Gln的生化代谢,揭示Gin代谢的关键环节,为依赖Gin的肿瘤提供治疗新策略。     

城市物质代谢的生态效率——以深圳市为例

城市可持续发展研究的关键是城市物质代谢通量及其效率研究,但物质代谢通量仅能反映代谢速率,而其生态效率则能反映支持社会经济发展的物质代谢能力。从工业、生活的源头循环(减少原生资源的消耗)和末端循环(减少污染物的产生)角度,构建城市物质代谢生态效率的度量模型,并依据中国城市化发展进程,选定深圳市作为研究区,核算城市水、能量和废物代谢通量以及代谢的生态效率。结果表明:随着深圳市社会经济的快速发展,水、能源和废物代谢通量呈现出增长势头,但代谢的生态效率不断提高。1998～2004年间,GDP增长2.7倍,城市水和电的代谢通量分别增长1.5倍和3.0倍;工业增加值增长3.7倍,工业水、电、能源和废物的代谢通量分别增长1.9、3.5、2.7倍和2.0倍;常住人口增长1.5倍,居民水和电的代谢通量分别增长1.8倍和1.7倍;资源效率提高1.8倍,环境效率提高3.7倍,生态效率提高2.3倍。虽然深圳市物质代谢的生态效率在提高,但是随着物质资源的日益稀缺,物质代谢的生态效率仍需进一步提高,而提高城市物质代谢生态效率的关键是资源效率和环境效率的协同发展,以及逐步构建废物资源化的循环链条。     

Systems biology of lipid metabolism: From yeast to human

Lipid metabolism is highly relevant as it plays a central role in a number of human diseases. Due to the highly interactive structure of lipid metabolism and its regulation, it is necessary to apply a holistic approach, and systems biology is therefore well suited for integrated analysis of lipid metabolism. In this paper it is demonstrated that the yeast Saccharomyces cerevisiae serves as an excellent model organism for studying the regulation of lipid metabolism in eukaryotes as most of the regulatory structures in this part of the metabolism are conserved between yeast and mammals. Hereby yeast systems biology can assist to improve our understanding of how lipid metabolism is regulated.     

Control of cell metabolism by the epidermal growth factor receptor

The epidermal growth factor receptor (EGFR) triggers the activation of many intracellular signals that control cell proliferation, growth, survival, migration, and differentiation. Given its wide expression, EGFR has many functions in development and tissue homeostasis. Some of the cellular outcomes of EGFR signaling involve alterations of specific aspects of cellular metabolism, and alterations of cell metabolism are emerging as driving influences in many physiological and pathophysiological contexts. Here we review the mechanisms by which EGFR regulates cell metabolism, including by modulation of gene expression and protein function leading to control of glucose uptake, glycolysis, biosynthetic pathways branching from glucose metabolism, amino acid metabolism, lipogenesis, and mitochondrial function. We further examine how this regulation of cell metabolism by EGFR may contribute to cell proliferation and differentiation and how EGFR-driven control of metabolism can impact certain diseases and therapy outcomes.     

城市代谢研究评述:内涵与方法

随着城市发展面临的生态问题日益显著,部分研究者试图通过对自然生态系统进行类比来寻求解决途径,城市代谢理论应运而生。当以系统科学来研究城市生态系统时,哲学思想的引入为探索和城市及城市代谢的内涵提供了最原始的桥梁。因此,在介绍城市代谢内涵与研究进展的基础上,融合产业、家庭、社会等多尺度代谢理论,对城市代谢的边界进行扩展,将其分为狭义与广义两类,结合亚里士多德的"四因说"对其质料因(组分)、形式因(结构)、动力因(驱动力)和目的因(功能)进行识别分析,据此将城市代谢研究方法归纳为质料、形式和混合研究方法三类,并提出未来研究的主要动向和解决手段。城市代谢"四因图"可为相关研究者提供参考。     

Effects of ethanol and phenobarbital administration on the metabolism and toxicity of benzene

Effects of ethanol- and phenobarbital(PB)-treatment on the metabolism of benzene in vitro and in vivo, and on the benzene-induced hemotoxicity, were investigated. Ethanol consumption markedly enhanced in vitro metabolism of both benzene and phenol in rat liver, whereas PB-treatment, which enhanced the metabolism of phenol to some degree (about one-third of ethanol-induced enhancement), did not affect the metabolism of benzene. In a single exposure experiment with rats, ethanol increased benzene metabolism in vivo as evidenced by accelerated disappearance of benzene from the blood as well as by elevated urinary excretion of phenol, whereas PB produced little or no significant influence on the metabolism. In a 3-week exposure experiment, ethanol administration accelerated benzene disappearance from the blood in agreement with the single exposure experiment, but it tended to decrease urinary phenol excretion with repetition of exposure, probably due to concomitant stimulation of subsequent phenol metabolism by ethanol. Again, PB-treatment produced only a negligible effect on the metabolism of benzene. Ethanol consumption aggravated benzene-induced hemopoietic disorder as evidenced by a marked decrease in the peripheral white blood cell number. PB produced a protective effect on the toxicity. It is concluded that ethanol potentiates benzene toxicity by accelerating (1) hydroxylation of benzene, a rate-limiting step of benzene metabolism and (2) transformation of phenol into highly toxic metabolites.