Biomedical Engineering Reference
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experimental approaches, computational techniques are likely to
The metabolic status of cells and whole organisms is ultimately
reflected in the composition of metabolites, and this, in turn,
is the result of the activities of metabolic enzymes. Measuring
metabolite concentrations may therefore be regarded as an activ-
itomic approach that quantifies the activity of metabolic enzymes
and pathways. Historically, NMR has been the method of choice
to profile metabolites in biological samples. However, the cur-
rent trend is to use LC-MS-based approaches, which are grad-
ually becoming the methods of choice because of their greater
Metabolomic techniques based on LC-MS are still in their
infancy. Indeed, although it is relatively easy to derive metabo-
lite profiles by MS and LC-MS, obtaining the identity of these
metabolites is not straightforward. This is because of the many
different chemical structures that form the backbone of these
small molecules, which makes deriving general rules for their
identification by MS/MS, analogous to those derived for pep-
tides, a very difficult, perhaps impossible, task. The field of
metabolomics will ultimately require the construction of compre-
hensive spectral libraries of metabolite CID MS/MS data, similar
to those already available for electron impact and chemical ion-
ization spectra.
Despite these technical limitations, LC-MS is increasingly
used for metabolic profiling and to quantify the fluxes of
metabolic pathways. In cancer research, metabolomic studies have
contributed to the notion that several metabolic pathways may
be altered in malignant cells. Cancer cells are characterized by
an increased proliferation rate and their ability to invade adjacent
tissue in hypoxic environments. Tumour cells therefore have dif-
ferent energy requirements than do normal cells, but as with sig-
nalling pathways, different cancer cells, even those of the same
pathology, may deregulate different metabolic pathways; in other
words, different tumours may obtain their energy via different
how these are regulated by known oncogenes and tumour sup-
pressors could be exploited in the design of novel therapeutic
strategies.
As an example of the use of LC-MS for the investigation
MS- and GC-MS-based metabolomic approach to profile 1,126
metabolites in 262 prostate cancer samples. Sarcosine (methyl-
glycine) concentrations were found to be greater in the plasma of
prostate cancer patients with metastatic disease relative to patients
with localized disease and benign tumours. This elevated sar-
cosine level probably reflects a greater activity of the enzyme
2.1.2.Metabolomics
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