Pharmacometabolomics Flashcards
What is metabolomics?
Comprehensive identification and quantification of all metabolites with a biological system
Truer representation of phenotype vs. genomics or transcriptomics
What is pharmacometabolomics?
This approach is understanding patient’s response to therapy from a metabolism perspective
ex. comparing metabolic signature before and after drug exposure (metabolic signature could one day help us optimize therapy, perhaps in the future)
Why are metabolite biomarkers so clinically useful?`
Metabolites are characterised by their high dynamic flux
- Changes in metabolites concentrations in response to a stimulus occur within seconds
- Changes at the metabolite level often appear in biological fluids before the appearance of clinical symptoms
What is an accessibility advantage for metabolite biomarkers?
They can be valuable diagnostic and prognostic biomarkers that can be routinely detected/quantified in typical clinical settings
What are some technologies used in metabolomics?
- NMR (Nuclear Magnetic Resonance)
- Mass Spectrometry (LC-MS, GC-MS)
What is the difference between targeted and untargeted metabolomics?
- Targeted metabolomics quantifies the specific metabolites in biological samples
- Untargeted metabolomics conduct a global metabolic profile of biological samples
What are some challenges associated with metabolomics?
- Diverse classes of low-molecular weight compounds (less than 1500 Da)
- Exist in very wide concentration ranges (some are high while others are low)
- Affected by genetic and environmental stimuli
- Not specific to a single metabolic pathway
- Heterogeneous physicochemical properties
What are the characteristics of blood metabolites?
Advantages:
- Easy to collect
- Instant reflection of metabolome
Disadvantages:
- Complex
- High protein content
- Needs extraction
What are the characteristics of urine metabolites?
Advantages:
- Non-invasive
- Low infection risk to researchers
- Normalization techniques available
Disadvantages:
- High salt conteent
- Affected by age, gender, day, food
What are some characteristics of saliva metabolites?
Advantages:
- Non-invasive
Disadvantages:
- Low concentration
- No established assay
What are some characteristics of exhales breath condensate metabolites?
Advantages:
- Non invasive
- Contains volatile metabolites
Disadvantages:
- Low concentration
- No normalization techniques
- Affected by alcohol, smoking, exercise
What are some characteristics of tissue sample metabolites?
Advantages:
- Real relection of the diseased organ
Disadvantage:
- Invasive
What is contained in the HMDB database?
It is a detailed catalog of small molecule metabolites found in the human body (chemical, clinical. molecular biology/biochemistry data)
What concentration separates abundant or relatively rare metabolites?
More than 1 microM, abundant
Less than 1 microM, relatively rare
Which level of “omics” study shows the impact of environmental factors?
Metabolomics
Environemental factors at later stages are not considered in genomics, transcriptomics, and proteomics
