Metabolomics: Concept, methods and potential prospect in marine biology
SPECIAL TOPIC Omics in Marine Biotechnology
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ZHANG Xuan
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CHEN Hao
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metabonomics, metabolomics, biosynthetic pathway, NMR, LC/GC-MS
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Key Laboratory of Marine Biological Active Substances, The First Institute of Oceanography
, State Oceanic Administration, Qingdao 266061,
China
The term omics refers to the comprehensive analysis of a specific biological system. With the development of omics, a number of omics subdisciplines have emerged, which play an important role in system biology. As a subdiscipline of omics, metabolomics provides a comprehensive analysis of the metabolome and has been widely applied to various fields of biology. In this paper, we introduce the concept, approaches, applications, and promising prospects of metabolomics.
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The complete sequencing of the human genome has
introduced a new field of systems biology, known as omics. In
biology, the term omics, which means the totality of sorts,
refers to the comprehensive analysis of a specific biological
system. For example, genomics is the study of all the
genes of a cell or tissue at the DNA (genotype), mRNA
(transcriptome) or protein (proteome) level [1]. Omics is an
integrated concept that combines all the information
acquired from the different levels at which biological systems
are controlled to investigate the nature of biological
phenomena at the molecular level. Compared with traditional
biological ideology, omics places more emphasis on the
integration of diverse bioinformation. Thus, it provides a
general view of processes rather than detailed information
on the independent behaviors of specific cells or tissues. To
date, a range of omics subdisciplines have emerged,
including genomics and proteomics, each of which has its own set
of instruments, techniques, reagents, and software. Omics
technology has driven the development of new research
approaches, including DNA and protein chips, mass
spectrometry, and instruments that enable high-throughput
analysis. Omics not only offers the advantage of understanding
biological processes, but the prospect of more accurate
diagnoses, improvements in nutrition and other new
applications in biological fields.
Nicholson first propounded the concept of metabonomics
in 1999. The primary definition of metabonomics is the
quantitative measurement of the dynamic multiparametric
metabolic response of living systems to pathophysiological
stimuli or genetic modification [2]. Metabonomics focuses
on understanding the global biological system by the study
of metabolic compounds. The early study of metabonomics
was focused primarily on the application of nuclear
magnetic resonance spectroscopy (NMR) to analyze the changes
of metabolic compounds in biological fluids, cells, and
tissues, and was aimed at the augmentation and
complementation of the information provided by measuring the genetic
and proteomic responses to xenobiotic exposure [2].
Another important subject in the study of metabolic
compounds is metabolomics. The focus of metabolomics is
the compositional analysis of low molecular-weight
substance in biological samples. This approach traditionally
uses MS (Mass Spectrometry) in combination with a
separation technique such as gas chromatography (GC) or liquid
chromatography (LC) to analyze information from low
molecular-weight compounds. To avoid interaction between
The Author(s) 2012. This article is published with open access at Springerlink.com
the compounds being measured in the matrix, sample
preparation and analysis is focused on a series of compounds
that share similar properties. The comprehensive
identification and quantification of the metabolic compounds
synthesized by an organism means that metabolomics is one of the
most important approaches to study genetic expression and
proteomics.
Although there is conceptual similarity between the
fields of metabonomics and metabolomics, there are some
significant differences in the approaches and objectives of
the research. The former is dedicated to comprehensive
metabonomics profiling at a given scale, whereas the latter
is primarily concerned with the history of time-dependent
metabolic profiles in an integrated system [3]. However,
associated with the development of bioinformatics, the two
concepts will likely be integrated. For convenience, we use
the term metabolomics in the following discussion.
An organism is an integrated and networked system with
a bioinformatics transport chain consisting of
genes-proteinsmetabolic compounds. Genes and proteins provide
information about what will happen, whereas metabolic
compounds provide information about what has happened. In
comparison with other omics subdisciplines, metabolomics
is defined by the following unique characteristics: (1)
Metabolic data do not provide the information produced by the
independent behaviors of specific cells or tissues but,
instead, documents the global changes of metabolome under
the external interference, which reflect the metabolic
response to exogenous stimuli in a general view. (2)
Metabolic compounds are the endpoint of functional gene activity.
According to Johnsons research, metabolic throughput is
not only controlled by genetic expression, but also adjusted
by the exogenous environment [4]. The changes in
concentrations of metabolic compounds illustrate the biological
response to perturbation from outside. Therefore, metabolic
compounds are more sensitive compared with genes and
proteins. (3) During a biochemical reaction, the
concentration of enzymes and metabolic throughput is generally
unchanged, whereas the concentration of some low-molecular
weight compounds will change significantly. Being the
endpoint of the bioinformatic transport chain, the signal
generated by alteration of the metabolome is magnified and
can provide insight and accurate characterization of the
cells function [5].
Progress in metabolomics
Pharmacotoxicology involves studying the toxicity of drugs,
their effect on target organs, their latency, and the
relationship between structure and toxicity. After being taken into
an organism, a heterologous substance acts directly on the
metabolome, but has no apparent effect on the genome or
proteome. Thus, there is little value in using genomics and
proteomics to evaluate the mechanisms of drug toxicity.
Traditional drug screening depends primarily on biological
screening, which is reliant on large sample sizes and is time
consuming. The advent of high throughout metabolomics
technologies means it is now possible to analyze large
numbers of samples in a relatively short period of time. Using
metabolomics technologies, we are able to detect abnormal
changes in trace materials in biofluids such as urine, serum,
and tissue biopsies following exposure to a heterologous
substance. In addition, these technologies allow for
simultaneous quantification of total metabolic compounds. For
example, Zhou et al. [6] injected dexamethasone into a
group of mice at day 17.5 of pregnancy then collected (...truncated)