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“Omics” experiments amass large amounts of data requiring integration of several data sources for data interpretation. For instance, microarray, metabolomic, and proteomic experiments may at most yield a list of active genes, metabolites, or proteins, respectively. More general ...

In the area of toxicology, the subdiscipline of toxicogenomics has emerged, which is the use of genome-scale mRNA expression profiling to monitor responses to adverse xenobiotic exposure. Toxicogenomics is being investigated for use in the triage of compounds through predicting pot ...

Metabolic Control Analysis (MCA) provides a conceptual framework for understanding the control of fluxes though metabolic pathways at the molecular level. It further provides a theoretical underpinning for an experimental approach to determining metabolic control. In this ch ...

In modern metabolomics, cellular reactions are observed as an integrated and networked system, termed as the metabolic network, instead of individual enzymatic reactions. Based on the metabolic network quantitated in terms of fluxes which are the rates at which materials are processed ...

Identifying and quantifying metabolites in complex biological samples is one of the most challenging aspects of metabolomics. Recently, several important advances in databases, software, instrumentation, and laboratory techniques have greatly simplified the most labor ...

In this chapter, the basic principles of high-resolution NMR relevant to metabolomics are reviewed, with an emphasis on practical aspects of experimental design, execution, and interpretation of the spectral data. This includes one- and two-dimensional NMR with isotope-editing te ...

Inductively coupled plasma-mass spectrometry is a versatile technique for rapid multielement analysis of metabolomic samples. It allows analysis of elements in solution or solids at the major, minor, or trace component levels in a very wide range of sample matrices. Laser Ablation, Gas Ch ...

Structural mass spectrometry (MS) is a chemical structure-revealing analytical technique that measures mass/charge ratio of ions. Biochemical analyses in the context of metabolomics—which seeks chemical descriptions of cellular, organismal, and even community biology— ...

Clinical metabolomics using stable isotope tracing represents an important new approach to obtaining metabolic parameters in human subjects in situ. In this chapter, the considerations for such clinical metabolomics are outlined and discussed. Descriptions include the esse ...

Sample preparation is the gateway to metabolomic analysis, the importance of which cannot be overemphasized. There are general rules of thumb for sample preparation that help maximize sample integrity and metabolite recovery. The wide range of variations in metabolite functional g ...

We provide an overview of metabolomics in its current practices, including sample processing, major techniques, example applications, and useful resources to the readership, as described in detail in the various chapters of the handbook. In our view, metabolomics can be defined as “a syst ...

The study of the metabolome or systems biochemical functions in response to external agents such as drugs or toxicants is made possible by recent advances in NMR and mass spectrometry. By coupling the analytical technologies with the stable isotope tracer approach, it is also practical to map c ...

Metabolomics analysis provides a window to the phenotypic responses to stimuli, including disease states and drug interventions. These responses are the end result of complex processes encoded by the organism’s genome. This chapter describes a computational set of tools that can be of gr ...

As the roles of phospholipids continue to be unraveled in an expansive list of biological processes, the availability of fast, accurate, and precise analytical approaches becomes of utmost relevance. Traditional methods rely on the separation of phospholipid classes, each with a diff ...

Metabolism is an interconnecting network of metabolite consumption and creation. Metabolomics has focused on metabolite concentrations in metabolic networks. Fluxomics is also required in the study of metabolism and quantifies the flux of substrate through each reaction step or a ...

Reaction phenotyping is the process of identifying in vitro the drug-metabolizing enzymes involved in the clearance of a drug in order to predict whether the drug might be susceptible to changes in its exposure or to cause changes in the exposure of concomitantly administered drugs. The semi- ...

Glucuronidation, catalyzed by the UDP-glucuronosyltransferases (UGT), is a major drug clearance mechanism in humans and other mammalian species. UGT reaction phenotyping involves determining which of the 19 known human UGTs are primarily responsible for glucuronidation of a p ...

The methods and materials described in this chapter are for a medium throughput screening assay for the study of parallel CYP- and UGT-mediated metabolic pathways in microsomes. Alamethicin, a pore-forming peptide, was used to activate UGTs in human liver microsomes. An alamethicin-mic ...

Hepatic metabolism is often a major contributor to drug clearance from the body, highlighting the utility of in vitro liver systems to address chemotypes that undergo extensive metabolism. Drug metabolism can be assessed in a variety of in vitro test systems, including microsomes, cytosol ...

Compound solubility and permeability play an important role in oral absorption of drug candidates and ultimately their Biopharmaceutics Classification System (BCS) classification. BCS classification of drug candidates can influence the drug development path, specific ...