טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentFlor Oshrat
SubjectSteroidal Metabolic Fingerprints of Basic Phenotypic
Characteristics based on Gas-Chromatography Mass-
Spectrometry and Bioinformatics
DepartmentDepartment of Medicine
Supervisors Professor Emeritus Zeev Hochberg
Dr. Carlos Knopf
Full Thesis textFull thesis text - English Version


Abstract

Metabolomics is the study of complex metabolite profiles in biological samples.

Of particular interest to metabolomics are small, low-molecular-weight compounds that serve as substrates and products in metabolic pathways. These compounds are very diverse in their physical and chemical properties and occur in a wide concentration range. Actually, much of the activity occurs at the metabolite level such as: cell signaling, energy transfer, cell-to-cell communication, etc.

Metabolomics has two definitions:

Metabolic profiling which focuses on the analysis of a group of metabolites either related to a specific metabolic pathway or a class of compounds.

Metabolic fingerprinting which compares patterns or ‘‘fingerprints’’ of metabolites that change in response to disease, toxin exposure, environmental or genetic alterations.

For metabolite analysis we use GC-MS which is currently the most popular instrument for global metabolic profiling. It is long established, is relatively cheap and can resolve complex biological mixtures.

Our study group comprised 39 healthy children and adults (11 children, 14 men and 14 women). For men and women six phenotypic profiles were measured (age, height, weight, BMI and blood pressure- systolic and diastolic). For children, four phenotypic profiles were measured (age, height SDS, weight, BMI SDS).

Subsequent analyses of the influence of gender and each phenotype on hormonal and enzymatic variables were performed.

We extend our interest beyond metabolite levels to also cover enzyme functions. To this end we evaluated differences between all quotients of pairs of metabolite levels as well as complex ratios of groups of metabolites.

We also used non-parametric methods adapted from gene expression data analysis to analyze metabolite profiles as derived from GC-MS data.

Results: There are many results within this text; nevertheless, some results are extremely significant:

1.      Decrease in 17,20,-Lyase enzymatic activity, which is responsible for weak androgen formation, as females age progresses,

2.      Increase in 21-OH’ase enzymatic activity, mainly in the glucocorticoid but also in the mineralocorticoid pathway, as males BMI and systolic blood pressure increases.

3.      Increase in all pathways leading to androgen formation as females BMI increases, a finding that matches a lot of other reports. 

4.      Significant decrease in the enzymatic activity of 11β-HSD1 as female's height increases.