Chemistry term index   Drug discovery term index   Informatics term index   Technologies term index    Biology term index   Site Map  Related glossaries include Applications: Biomarkers   Drug safety, pharmacovigilance & toxicology   Functional genomics  Pharmacogenomics  Informatics Genomic Informatics  Protein Informatics    Technologies Cells & Tissues Technologies  Microarrays  Biology: Cell biology   Expression

Alliance for Cellular Signaling AfCS: The overall goal of the Alliance for Cellular Signaling is to understand as completely as possible the relationships between sets of inputs and outputs in signaling cells that vary both temporally and spatially. The same goal, stated from a slightly different perspective, is to understand fully how cells interpret signals in a context- dependent manner.  Alliance for Cellular Signaling website http://www.cellularsignaling.org/  Related terms: cellular signaling, signal transduction

biochemical feedback: A mechanism of communication among life processes to coordinate development, reproduction, and homeostasis. In humans, feedback loops are especially important for communication between organs that are spatially separated. Virtually all hormones from the nervous and endocrine systems are under feedback control: by peripheral hormones, cations, metabolites, osmolarity or extracellular fluid volume. MeSH, 2002

biochemical networks: Biochemical networks are the central processing units of life. They can perform a variety of computational tasks analogous to electronic circuits. Their design
principles, however, are markedly different: in a biochemical network, computations are performed by molecules that chemically and physically interact with each other. Biochemical Networks group, AMOLF, Amsterdam, Netherlands http://www.amolf.nl/research/biochemical-networks/ 

biochemical pathways: Traditionally, the term biochemical pathways has principally referred to metabolic pathways. These are the pathways by which a cell converts compounds that enter it into cellular components (e.g., small molecules and macromolecules including proteins, nucleic acids, storage carbohydrates, and fatty acids), and by which the cell derives energy. Allan Haberman, 2002  Related term: pathway determination    
Boehringer Mannheim Biochemical Pathways wall chart - digitized http://biochem.boehringer-mannheim.com/prodinfo_fst.htm?/techserv/metmap.htm

biological networks: Expression

BioPathways Consortium: Researchers are poised to begin the next phase of  elucidating how living systems function. This involves the identification of  genes and their functions, followed by their organization according to their roles and interactions within  the more global context of cellular  mechanisms. Constructing representations of the latter will involve not only structural information, but more dynamic and causal forms relevant to  biochemical processes ... there is an urgent need to discuss and develop new informatics technologies  that will support such new forms of biological information. Data regarding  pathways and interactions is already being accumulated in dozens of different formats, but no standard way of representing or exchanging them exists to date. [BioPathways Consortium "Vision"]  http://www.biopathways.org/

BioPAX: Biological Pathways Exchange http://www.biopax.org/ 

cellular pathways:  The 20 microns between the cell membrane and the genetic material in the cell nucleus is the playground of the molecules of signal transduction, of the intricate and multifaceted redundancy of the pathways that take signals from the membrane and convert them into the exquisitely selective control of our genes. Within these pathways, the regulation of gene transcription is carried out by a multitude of hormones and growth factors, which in turn are affected by environmental stresses and a host of other phenomena. "UCSD's Michael Karin follows the cellular pathways" ScienceWatch, Mar-Apr. 1999 http://archive.sciencewatch.com/march-april99/index.html   See also under metabolic engineering

cellular signaling: The overall goal of the Alliance for Cellular Signaling is to understand as completely as possible the relationships between sets of inputs and outputs in signaling cells that vary both temporally and spatially. The same goal, stated from a slightly different perspective, is to understand fully how cells interpret signals in a context- dependent manner. This will involve identification of all the proteins that comprise the various signaling systems, the assessment of time- dependent information flow through the systems in both normal and pathological states, and finally the reduction of the mass of detailed data into a set of interacting theoretical models that describe cellular signaling. Alliance for Cellular Signaling Homepage http://www.cellularsignaling.org/

comparative metabolomics: Omes & omics
Flux Balance Analysis FBA: See under Metabolic Control Analysis MCA
fluxome, fluxomics : Omes & omics
functional/metabolic imaging: Molecular imaging 
functional metabolics: Related terms: metabolic profiling; Expression; Omes & omics metabolome, metabolomics, metabonome, metabonomic

gene regulatory pathways: The association of a particular gene regulatory pathway with a disease process may lead to the identification of critical targets within these pathways. ... A considerable body of evidence already suggests that transcription factors themselves (i.e., key components of gene regulatory pathways) can be disease- gene products and/ or drug targets  , Allan B. Haberman,  2002

interactions- molecular: Related terms: Biomolecules biomolecular interactions; Omes & omics interactome; Proteomics protein- DNA interactions, protein- protein interactions, protein- RNA interactions; Sequences, DNA & beyond: RNA- RNA interactions

in vitro screens -- drug metabolism:  Predicting how a drug will behave in humans before clinical testing requires a battery of sophisticated in vitro tests that complement traditional expensive in vivo safety assessments. In vitro assays attempt to mimic in vivo conditions but always involve an element of uncertainty. One approach to solving this problem has been the use of in vitro screens to identify early on the characteristics of a new chemical entity (NCE), particularly with the respect to its metabolism.  Early drug metabolism models help predict a compound's elimination from the body, or metabolic stability, which affects its duration of action. More elaborate in vitro models can identify which enzyme systems play a role in elimination, which help predict drug- drug interactions, as well as the potential for the compound of interest to induce enzyme systems to eliminate other drugs. Finally, experimental design, standardized assays and assay conditions allow researchers to pool data and develop new predictive models.

metabolic biomarkers: Biomarkers

Metabolic Engineering ME: An approach to the understanding and utilization of metabolic processes. As the name implies, ME is the targeted and purposeful alteration of metabolic pathways found in an organism in order to better understand and utilize cellular pathways for chemical transformation, energy transduction, and supramolecular assembly. ME typically involves the redirection of cellular activities by the rearrangement of the enzymatic, transport, and regulatory functions of the cell through the use of recombinant DNA and other techniques. Much of this effort has focused on microbial organisms, but important work is being done in cell cultures derived from plants, insects, and animals. National Science Foundation, Interagency Opportunities in Metabolic Engineering,  Program Solicitation NSF 05-502, 2004 http://www.nsf.gov/pubs/2005/nsf05502/nsf05502.htm 

A new approach to understanding and using metabolic processes. As the name implies, ME is the targeted and purposeful alteration of metabolic pathways found in an organism in order to better understand and use cellular pathways for chemical transformation, energy transduction, and supramolecular assembly. Knowledge acquired from this research will benefit society in a number of ways, including the ability to modify biological pathways to produce biological substitutes for less desirable chemical processes; allowing greater agricultural production, permitting more efficient and safer energy production, and; providing better understanding of the metabolic basis for some medical conditions that could assist in the development of new cures. [US EPA, Metabolic Engineering Working Group, 2002] http://www.epa.gov/opptintr/metabolic/

metabolic fingerprinting: For functional genomic or plant breeding programmes, as well as for diagnostic usage in industrial or clinical routines, it might not be necessary to determine the levels of all metabolites individually.  Instead, a rapid classification of samples according to their origin or their biological relevance might be more adequate in order to maintain a high throughput.  This process can be called metabolic fingerprinting.  Oliver Fiehn "Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks" Comparative and Functional Genomics 2: 155-168, 2001 http://onlinelibrary.wiley.com/doi/10.1002/cfg.82/full 

metabolic networks: To further test the biological relevance of hypotheses gained from metabolomic data sets, these data should be compared to predictions made either by searching connections to known biochemical pathways, or by using prediction models based on mathematical calculations from biochemical kinetics or stoichiometries. Oliver Fiehn "Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks" Comparative and Functional Genomics 2: 155-168, 2001 http://downloads.hindawi.com/journals/cfg/2001/914970.pdf   Wikipedia http://en.wikipedia.org/wiki/Metabolic_network 

metabolic network modelling: Wikipedia http://en.wikipedia.org/wiki/Metabolic_network_modelling 
metabolic pathway: Wikipedia http://en.wikipedia.org/wiki/Metabolic_pathway 

metabolic pathways: As represented, for example, in popular wall charts of such pathways) are usually seen as step- by- step sequences by which the cell carries out interconversion of small molecules (e.g., glucose to pyruvate in glycolysis), synthesizes components (amino acids and nucleotide triphosphates) for protein and nucleic acid biosynthesis, and breaks down storage macromolecules (e.g., glycogen and fatty acids) into small molecules for energy metabolism. Since each step of a metabolic pathway is catalyzed by an enzyme, it is these enzymes that are of most interest with respect to the genomics of metabolic pathways. 

To understand cellular function, most scientists study parts of specific biochemical pathways, such as the cell cycle, that involve individual molecules, cells, groups of cells, and whole organisms. The goal is, of course, to be able to put all the parts together to understand normal cellular activities and how they malfunction in disease.  National Institute of General Medical Sciences, Inside the Cell, 2005 http://www.nigms.nih.gov/news/science_ed/life.html   

Protein-protein interactions are sometimes confused with metabolic pathways. Metabolic Pathway is a series of enzyme- catalyzed reactions. Each reaction produces a product which becomes the substrate for the next reaction. Although the structures of metabolic pathways and protein interaction maps are similar, there are a number of significant differences: While metabolic pathways focus on the conversion of small molecules and the enzymes responsible for these conversions, protein interaction maps concentrate mainly on physical contacts without obvious chemical conversions. Physical interactions are certainly of great utility when one studies single proteins or defined biological processes, but themselves do not reflect the huge amount of knowledge that has been accumulated in the biological literature: Diana Abdueva --- Tina Hu --- Keiichiro Ono --- John Zhong,  Classical and Reverse Proteomics, Computational Molecular Biology Laboratory, Univ. of Southern California, US http://hto-b.usc.edu/~cbmp/2002/ProteinInteraction/part2/m577bpart2.html#Mapping%20

metabolic phenomics: Omes & omics

metabolic profiling:  Metabolic profiling employs a range of analytical approaches (e.g., mass spectrometry and high- resolution ¹H nuclear magnetic resonance spectroscopy) suited to the chemical properties of the metabolite class(es) of interest. Bioinformatic tools are used to maximize information recovery from biofluid samples and to aid interpretation of the very large multivariate metabolite data sets that are created. Metabolic profiling can be applied to multiple levels of biological organization, ranging from single cells to whole organisms. Perhaps the greatest interest has been on the metabonomic analysis of integrated body pools such as urine and plasma, as these pools reflect systems- wide phenotypic response(s). In such case, metabonomics provides an integrated readout of both primary and secondary perturbations that point to a pathophysiologic process, genetic modification, or xenobiotic exposure. ["Metabonomics: Mining for Metabolites in Biofluids" Environmental Health Perspectives 110 (3) March 2002] http://ehpnet1.niehs.nih.gov/docs/2002/110-3/extram-speaking.html

In the context of drug research or pesticide metabolism, the term metabolic profiling is frequently used to describe the metabolic fate of an administered drug. Oliver Fiehn "Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks" Comparative and Functional Genomics 2: 155-168, 2001 http://downloads.hindawi.com/journals/cfg/2001/914970.pdf  Related terms: functional metabolics; Expression metabolite expression, metabolite systems biology, molecular profile; Omes & omics metabolomics, metabonomics; Research NIH Roadmap  Broader term profiling Narrower terms: in vitro screens for drug metabolism, metabolic flux profiling

metabolic syndrome: Molecular Medicine

metabolics: Metabolome projects are now generally accepted as parts of all integrated genome wide efforts in bacteria, yeast, Arabidopsis and man. ...  Data from metabolic profiling studies have been shown to be reliable indicators and predictors of a cell or organisms physiological state (e.g. actively growing, diseased, etc.). Current estimates point to over 500 human diseases with direct defects in metabolism. More complex diseases such as cancer, are also known to involve metabolic changes. Capturing this metabolic information by observing the broadest possible class of molecules and relating it to changes in the transcriptome and proteome remain a daunting challenge for the field of metabolomics.  John Hamer, Imperial College and Metabometrix, "Metabolics: Future Prospects and Challenges" Metabolic Profiling Dec. 3- 4, 2001 Chapel Hill, NC  Related terms: Omes & omics

metabolism: In case of heterotrophic organisms, the energy evolving from catabolic processes is made available for use by the organism.   IUPAC Medicinal Chemistry

The sum of chemical changes that occur within the tissues of an organism consisting of anabolism (BIOSYNTHESIS) and catabolism; the buildup and breakdown of molecules for utilization by the body. MeSH

The total fate of a xenobiotic, which includes: absorption, distribution, biotransformation, metabolism and elimination (ADME). Metabolism and biotransformation are often used interchangeably, but the latter term does not encompass absorption, distribution and elimination.  Glossary, XenoTech LLC http://xenotechllc.com/Knowledge/Glossary/ 
Metabolism, Wikipedia, accessed May 27, 2004 http://en.wikipedia.org/wiki/Metabolism distinguishes between total metabolism, specific metabolism, cell metabolism and other types of metabolism.  Narrower term: metabolism- medicinal chemistry

metabolite: Any intermediate or product resulting from metabolism. IUPAC Biotech

metabolite profiling: For investigators of selected biochemical pathways, it is also often not necessary to view the effects of perturbation on all branches of metabolism. Instead, the analytical procedure can be focused on a smaller number of pre- defined metabolites. Sample preparation and data acquisition can be focused on the chemical properties of these compounds with the chance to reduce matrix effects. This process is called metabolite profiling (or sometimes metabolic profiling). Oliver Fiehn "Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks" Comparative and Functional Genomics 2: 155-168, 2001 http://downloads.hindawi.com/journals/cfg/2001/914970.pdf  See also metabonomics

metabolomics: -Omes & -omics; Pharmacogenomics

metabolon: The coordinated channelling of substrates through tightly connected enzyme complexes. Oliver Fiehn "Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks" Comparative and Functional Genomics 2: 155-168, 2001 http://downloads.hindawi.com/journals/cfg/2001/914970.pdf 

Enzymes of metabolic pathways are nowadays thought to be clustered and operate as 'metabolons'.  S. Beeckmans et. al., "Immobilized enzymes as tools for the demonstration of metabolon formation. A short overview" Journal of  Molecular Recognition 6 (4): 195- 204 Dec. 1993] 

metabonomics: -Omes & -omics
molecular networks:  Molecular networks are composed of pathways. 
molecular profiling: Expression gene and protein

network dynamics:  Network analysis has been applied widely, providing a unifying language to describe disparate systems ranging from social interactions to power grids. It has recently been used in molecular biology, but so far the resulting networks have only been analysed statically^{1, 2, 3, 4, 5, 6, 7, 8}. Here we present the dynamics of a biological network on a genomic scale, by integrating transcriptional regulatory information^{9, 10, 11} and gene-expression data^{12, 13, 14, 15, 16} for multiple conditions in Saccharomyces cerevisiae. We develop an approach for the statistical analysis of network dynamics, called SANDY, combining well-known global topological measures, local motifs and newly derived statistics. Genomic analysis of regulatory network dynamics reveals large topological changes Nicholas M. Luscombe^1,5, M. Madan Babu^4,5, Haiyuan Yu¹, Michael Snyder², Sarah A. Teichmann⁴ & Mark Gerstein Nature 431, 308-312 (16 September 2004) | doi:10.1038/nature02782; Received 15 January 2004; Accepted 24 June 2004 http://www.nature.com/nature/journal/v431/n7006/abs/nature02782.html 

networks: Although there is no consensus definition of "program" or "networks", these terms are most often encountered and understood in the context of the regulatory interactions that link groups of genes and gene products in developmental processes.  Many of these linkages have recently been elucidated in considerable detail for key events in a variety of species. Sean Carroll "Communications breakdown?" (book review) Science 291: 1264-1265, Feb. 16, 2001

The experimental task of mapping genetic regulatory networks using genetic footprinting and [yeast] two- hybrid techniques is well underway, and the kinetics of these networks is being generated at an astounding rate. Technology derivatives of genome data such as gene expression micro- arrays and in vivo fluorescent tagging of proteins through genetic fusion with the GFP [Green fluorescent] protein can be used as a probe for network interaction and dynamics. If the promise of the genome projects and the structural genomics effort is to be fully realized, then predictive simulation methods must be developed to make sense of this emerging experimental data. There are three bottlenecks in the numerical analysis of biochemical reaction networks. The first is the multiple time scales involved. Since the time between biochemical reactions decreases exponentially with the total probability of a reaction per unit time, the number of computational steps to simulate a unit of biological time increases roughly exponentially as reactions are added to the system or rate constants are increased. The second bottleneck derives from the necessity to collect sufficient statistics from many runs of the Monte- Carlo simulation to predict the phenomenon of interest. The third bottleneck is a practical one of model building and testing: hypothesis exploration, sensitivity analyses, and back calculations, will also be computationally intensive. Lawrence Berkeley Lab "Advanced Computational Structural Genomics" Glossary  Narrower terms: biochemical networks, molecular networks  

pathway analysis: Getting Started in Biological Pathway Construction and Analysis PLOS 2008  http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0040016
Wikinomics http://openwetware.org/wiki/Wikiomics:Pathway_analysis

pathway engineering: Modifying a cell’s physiology to improve its capacity to overproduce a desired molecule for industrial use is referred to as Pathway Engineering. Genencor, Danisco A/S 2007  http://www.genencor.com/wps/wcm/connect/genencor/genencor/technology/expressionx_secretion/pathway_engineering/pathway_engineering_en.htm

pathway specificity: As a rough generalization, receptors on the cell surface and transcription factors in the nucleus are often dedicated to specific pathways or groups of pathways. The receptors and transcription factors are connected by chains made up principally of molecules that are involved in many types of signaling pathways. (Regulation of transcription of sets of genes by specific transcription factors forms the basis for gene regulatory networks.  Allan B. Haberman,  2002  

pathways:  A general term meant to include all forms of  molecular transactions and processes that are part of  biochemical systems. Some of these pathways may involve linear processing, but many involve complex branches, convergences, and even cycles. .... There are several different classes of biochemical pathways: metabolic pathways, signal transduction cascades, genetic networks, and drug metabolism pathways. In addition, protein interaction data  links protein data objects, and can therefore also be conceptualized as graphs. Although the relationship of  protein- interaction maps with biochemical pathways is undeniable, it is not obvious. ... the design of  adequate models for bio- process representation, manipulation and simulation is still a very open field of research. In conclusion, we will need to examine and discuss the relationships between all pathway information, protein interaction data, and biological process information in order to successfully produce informatics specifications for any of these kinds of  data.  Biopathways Consortium "Definition" http://www.biopathways.org/

The routes or processes by which genes and their products function in cells, tissues, and organisms. Pathways involving a particular gene or its product may be determined by two major types of methods. One involves identifying other proteins that specifically interact with the product of the gene of interest. The other involves carrying out specific genetic studies with model organisms.

The term biochemical pathways has principally referred to metabolic pathways, which are the pathways by which a cell converts compounds that enter it into cellular components (e.g., small molecules and macromolecules including proteins, nucleic acids, storage carbohydrates, and fatty acids) and by which the cell derives energy. Signaling pathways are biochemical pathways that regulate cellular characteristics and processes such as physiology, proliferation, changes in shape and motility, differentiation, adhesion, and intercellular interactions. High- content screening approaches can be used to help elucidate pathways.  Narrower terms: biochemical pathways, gene regulatory pathways, metabolic pathways, signaling pathways  pathways databases: Databases & software directory

phenotypic profiling:  Despite our rapidly growing knowledge about the human genome, we do not know all of the genes required for some of the most basic functions of life. To start to fill this gap we developed a high-throughput phenotypic screening platform combining potent gene silencing by RNA interference, time-lapse microscopy and computational image processing. We carried out a genome-wide phenotypic profiling of each of the ~21,000 human protein-coding genes by two-day live imaging of fluorescently labelled chromosomes. Nature 2010  http://www.nature.com/nature/journal/v464/n7289/full/nature08869.html  Related terms: Genomics  phenotype, phenotyping

physiological genomics: The scope note for the journal Physiological Genomics indicates that it covers "a wide variety of studies from human and from informative model systems with techniques linking genes and pathways to physiology, from prokaryotes to eukaryotes. The Journal encourages the submission of research that links genes to cell replication, development, metabolic function, cell signal transduction and intracellular signaling pathways, tissue and organ function, and whole organism function. Physiological Genomics encourages the utilization of approaches ranging from expression profiling, assays for molecular interactions, natural and directed gene alteration, selective breeding studies, gene identification, and the assessment of gene/environment interaction. ... new computational approaches, integrative models, and image analysis predictive of gene function." [Physiological Genomics website "journal scope", American Physiological Society] http://physiolgenomics.physiology.org/misc/about.shtml

reaction phenotyping: Knowing how a drug candidate is eliminated by the human body is important in understanding the potential for drug-drug interactions.  Compounds with a single route of elimination have a high victim potential, which is why the FDA requires reaction phenotyping studies. Reaction phenotyping generally involves three types of analysis: correlation analysis, antibody and chemical inhibition, and metabolism by recombinant human CYP enzymes. Each has its advantages and disadvantages, and a combination of approaches is highly recommended.  http://www.xenotechllc.com/Services/Drug-Metabolism/Reaction-Phenotyping

regulatory networks: See under networks Related terms: Omes & omics regulome, regulomics
second messenger, second messenger systems: Cell biology

signal transduction: The intercellular or intracellular transfer of information (biological activation/ inhibition) through a signal pathway. In each signal transduction system, an activation/ inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/ enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA- AMINOBUTYRIC ACID- postsynaptic receptor- calcium ion channel system, the receptor- mediated T-cell activation pathway, and the receptor- mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor- mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. MeSH, 1989

Any process that helps to produce biological responses to events in the environment or internal milieu (e.g., transduction of light into nerve impulses by the retina or transduction of hormone binding into cellular events by hormone receptors). MeSH, earlier definition

Aberrant signal transduction is the cause of many of the most personally and financially devastating diseases challenged by modern medicine, including cancer, inflammatory diseases, cardiovascular disease and neuropsychiatric disease. In the search for treatments, cures, and preventions for these diseases, in depth understanding of the biology of signal transduction is a prime method for the discovery of appropriate disease targets and in the design of drugs to halt or prevent them. 

The intercellular or intracellular transfer of activation or inhibition signals through a so- called signaling pathway. These signals can be initiated, for example, when a biologically active molecule binds to a receptor. Signal transduction is involved in many cellular processes, including cell proliferation and differentiation. Related terms: pathway determination, physiological genomics
Signal transduction databases: Databases & software directory
Signaling Gateway, AfCS and Nature http://www.signaling-gateway.org/ Cell signaling research, including primary research and reviews, news, jobs and conferences,  Molecule Pages database
Signal Transduction Knowledge Environment, Science and Stanford Univ. http://stke.sciencemag.org/.  Updated weekly.

signaling pathways: Biochemical pathways that regulate cellular characteristics and processes such as physiology, proliferation, changes in shape and motility, differentiation, adhesion, and intercellular interactions. Examples include pathways by which hormones, growth factors, and cytokines regulate cellular processes. For instance, factors such as epidermal growth factor and insulin initiate signaling by binding to their specific receptors on the cell surface. Broader terms: pathways, biochemical pathways

signalome- plant: Omes & omics

Bibliography
CHI Biochemical Pathway and Systems Analysis for Target Identification and Validation report, 2002
FDA, Guidance for Industry, Safety testing of drug metabolites,  2008 http://www.fda.gov/CDER/GUIDANCE/6897fnl.pdf   
XenoTech LLC, Glossary, 2004, 70+ definitions  http://www.xenotechllc.com/Knowledge/Glossary/ 

Alpha glossary index

How to look for other unfamiliar  terms

IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry.