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The term "metabolome" was first used by Olivier et al. in

1998 to describe the set of metabolites synthesized by an
organism, in a fashion analogous to that of the genome and
proteome.

Some have limited this definition to "the quantitative

complement of all of the „
 „„

 „„
present in cells in a particular physiological or developmental
state".
 |


|etabolomics was coined by Oliver Fiehn and defined as a

comprehensive @ @ „  analysis in which „„ metabolites of
a biological system were @   and @  .
 |


|etabonomics is defined as "the quantitative measurement of the

dynamic multiparametric metabolic response of living systems to
pathophysiological stimuli or genetic modification".

There is a growing consensus that the difference resides in the fact

that 'metabolomics' places a greater emphasis on comprehensive
metabolic profiling, while 'metabonomics' is used to describe
multiple (but not necessarily comprehensive) metabolic changes
caused by a biological perturbation.
 |



woth |etabolomics and |etabonomics involve @ @ „  or

@ @  analysis.

In contrast µ|etabolite profiling¶ involves the identification

and quantitation by a particular analytical procedure of a
 @  of metabolites of known or unknown identity
and belonging to a selected metabolic pathway.
 ( 
|

ðinus Pauling hypothesised on the predictive
capacity of chromatographic profiling of bodily
fluids for detection and diagnosis of human disease.

Chromatographic separation techniques were

developed in the late 1960's.
Robinson and Pauling published ³Quantitative Analysis of Urine Vapor and
wreath by Gas-ðiquid Partition Chromatography´ in 1971.

The |etabolome and |etabolomics were coined in the 1990s.

In January 2007 the Human |etabolome Project, completed the first draft of
the human metabolome, consisting of 2,500 metabolites, 1,200 drugs and
3,500 food components.
|
    


Integration of genomics, transcriptomics, proteomics and
metabolomics is a goal of systems biology.
 §
 


 

It has been argued that metabolomics provides the most

"functional" information of the omics technologies.

Changes in the transcriptome and proteome do not always result in

altered biochemical phenotypes (the metabolome). The metabolome
represents the final "omic" level in a biological system, and metabolites
represent functional entities, unlike messenger RNA molecules, which
constitute the transcriptome. |etabolites thus have a clear function in the life
of the biological system and are also contextual, reflecting the surrounding
environment. The metabolome can thus be thought of as a looking glass, which
if looked through can show information concerning the physiological,
developmental, and pathological status of a biological system.
 §
  
   

|etabolomics was coined by Oliver Fiehn and defined as a

comprehensive @ @ „  analysis in which „„ metabolites of
a biological system were @   and @  .

It is estimated that the metabolome extends over 7-9 magnitudes

of concentration (pmol-mmol), and the number of metabolites in
the plants is estimated to exceed 200,000 and only about 10,000
are known.

It is not currently possible to analyse the entire range of

metabolites by a single analytical method.
  
 

{ifferent separation and detection methods can be

used either individually or in combination to detect
and quantify hundreds or perhaps thousands of
metabolites.
 V
(    

Gas chromatography
It offers high resolution, but requires chemical derivatization for many
biomolecules and only volatile chemicals can be analysed without derivatization.

Gas-liquid chromatography - involves

a sample being vapourised and
injected onto the head of the
chromatographic column. The sample
is transported through the column by
the flow of inert, gaseous mobile
phase. The column itself contains a
liquid stationary phase which is
adsorbed onto the surface of an inert
solid.
 V
(    

High performance liquid chromatography

HPðC has lower resolution than GC, but it does have the advantage that a much
wider range of analytes can potentially be measured.
 V
(    

Capillary electrophoresis
It has a higher theoretical separation efficiency than HPðC and is suitable for use
with a wider range of metabolite classes than is GC. As for all electrophoretic
techniques, it is most appropriate for charged analytes.
 V
(   


|ass spectrometry
Used to identify and to quantify metabolites after separation by GC, HPðC, or
CE. In addition, mass spectral fingerprint libraries exist that allow
identification of a metabolite according to its fragmentation pattern.

Sector instrument
There are many types of mass
spectrometers that not only
analyze the ions differently but
produce different types of ions;
however they all use electric
and magnetic fields to change
the path of ions in some way.
 V
(   


Nuclear magnetic resonance (N|R) spectroscopy

N|R is almost the only detection technique which does not rely on extraction
and separation of the analytes, and the sample can thus be analysed in vivo and
recovered for further analyses.

Any molecule containing one or more atoms with a non-zero magnetic moment
can potentially be detected. In practice metabolites are labelled by feeding
substrates containing 1H, 13C, 14N, 15N or 31P isotopes.

N|R is close to being a universal detector. However, it possesses one major

disadvantage, which is that it is relatively insensitive compared to mass
spectrometry-based techniques.
 
  




Similar issues to transcriptomics and proteomic data sets.

Use of multivariate statistical analysis is most common.

 |
 V


{iagnosis

{isease (e.g. coronary heart disease).

Toxicology

Functional genomics

Ascribing functions to genes

Systems biology

Integration with data sets from other omics.

 ` 

|etabolomics:

Probably none

|etabonomics and metabolite profiling:

|any
 ` 
A flux map for v   .
Gombert et al., (2001)  „. 183, 1441-1451.

The fluxes were estimated through

feeding the cells with 13C-labelled
glucose, analysis of the isotopomers of
the intracellular metabolites, and analysis
of the data using the mathematical model
of the metabolism. In the wild-type strain
there is glucose repression on respiration
thus the flux through the TCA cycle is
low. When  is deleted (italics) there
is a de-repression of respiration and the
flux through the TCA cycle therefore
increases.
 ` 
Rubisco improves the carbon efficiency of developing green seeds.
Schwender et al., (2004) d 432:779-782.

(

*  


*
 ` 
{iagnosis of coronary heart disease
wrindle et al., (2002) d  @8, 1439-1444.

The 600 |Hz 1H-N|R spectra of serum samples from a typical

NCA patient (?) and a TV{ (triple vessel disease) patient.

 ` 
Genetic regulation of glucosinolate accumulation in Arabidopsis
Keurentjes et al., (2006) d@  38, 842-849.

(V) QTð likelihood profiles of aliphatic glucosinolates detected in the recombinant inbred
line population. ( ) Second-order genetic correlations between aliphatic glucosinolates
detected in the recombinant inbred line population.
   

Reviews
Fiehn O. (2002) |etabolomics-the link between genotypes and phenotypes. Ԅ@ „ „. 48, 155-171.
Schauer N, Fernie AR. (2006) Plant metabolomics: towards biological function and mechanism. @ Ԅ@v . 11, 508-516.
Schnackenberg ðK, weger R{. (2006) |onitoring the health to disease continuum with global metabolic profiling and systems
biology. Ô
@    7, 1077-1086.
ðenz E|, Wilson I{. (2007) Analytical strategies in metabonomics. J Proteome Res. 6, 443-458.

Papers
wrindle, J. T.; Antti, H.; Holmes, E.; Tranter, G.; Nicholson, J. K.; wethell, H. W.; Clarke, S.; Schofield, P. |.; |cKilligin, E.;
|osedale, {. E.; Grainger, {. J. (2002) Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease
using 1H-N|R-based metabonomics. d  @8, 1439-1444.
Raamsdonk, ð. |., w. Teusink, {. wroadhurst, N. S. Zhang, A. Hayes, |. C. Walsh, J. A. werden, K. |. wrindle, {. w. Kell, J. J.
Rowland, H. V. Westerhoff, K. van {am, and S. G. Oliver 2001. A functional genomics strategy that uses metabolome data to
reveal the phenotype of silent mutations. d @ „
. 19, 45-50.
Gombert AK, |oreira dos Santos |, Christensen w, Nielsen J. (2001) Network identification and flux quantification in the
central metabolism of Saccharomyces cerevisiae under different conditions of glucose repression.  „. 183, 1441-1451.
Keurentjes JJ, Fu J, de Vos CH, ðommen A, Hall R{, wino RJ, van der Plas ðH, Jansen RC, Vreugdenhil {, Koornneef |.
(2006) The genetics of plant metabolism. d@  38, 842-849.