Metabolism is an integrated network of biochemical pathways involving a series of enzymecatalysed
anabolic or catabolic reactions in cells. Metabolites are chemical compounds that are
involved in or are products of metabolic pathways, and the metabolome is defined as the total
complement of all the low molecular weight metabolites present in a cell at any given time.
Metabolomics is a relatively new research technology utilised for the global investigation,
identification and quantification of the metabolome. Three aims were defined for the
metabolomics study presented here:
• The use of metabolomics technology to generate new biological information;
• Application of the metabolomics technology to gain information on the three natural
perturbations, namely the menstrual cycle, pregnancy and aging; and
• Reflection on metabolomic studies as a hypothesis-generating approach.
I obtained three sets of urine samples from women during their menstrual cycle, samples from
sixteen pregnant and eleven non-pregnant women for the second natural perturbation, and data
sets from previous investigations on infant and child groups, as well as thirty-two urine samples
from adults for the study of the metabolomic profiles due to age. These urine samples were
analysed to determine the organic acid metabolite profiles. The metabolites were identified by
means of AMDIS and were manually quantified. Data matrixes were compiled, which underwent
certain data reduction steps, prior to statistical analysis. Different statistical approaches were
used to generate information on these three natural perturbations due to the clear differences
between the three experimental groups used. The investigation of the menstrual cycle did not
show a distinct difference between the three phases involved in the cycle, whereas the
pregnancy perturbation showed a difference between pregnant groups and non-pregnant
groups. The most pronounced difference in metabolite profiles were found when the different
age groups were compared to one another. Finally a hypothesis on the effect of age on
metabolism was defined and an experimental approach was proposed to evaluate this
hypothesis.
In conclusion three proposals were formulated from this investigation:
1. If it appears that an insufficient number of participants can be generated for a
metabolomics study, such a study should be discarded in the interest of a more feasible
investigation.
2. It is advisable that a number of appropriate analytical validation parameters should be
incorporated in the early stages of a metabolomics study, specifically linked to the
context of the perturbation chosen for the investigation. 3. The control and experimental groups should be homogenous that is to say as
comparable as possible with regard to age, ethnicity, diet, and gender, lifestyle habits
and other possible confounding influences, except for the specific perturbation being
studied. In a perfect world this would be possible, specifically when hypothesis
formulation, testing and finally the expansion of scientific knowledge is a desired
outcome of the investigation. / Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2010.
| Identifer | oai:union.ndltd.org:NWUBOLOKA1/oai:dspace.nwu.ac.za:10394/4219 |
| Date | January 2010 |
| Creators | Davoren, Elmarie |
| Publisher | North-West University |
| Source Sets | North-West University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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