WEEKS 3&5 Flashcards
Define nutrigenomics
Nutrigenomics is the study of how nutrients in the diet can effect health through modulation of gene expression
Define nutrigenetics
Nutrigenetics is the study of how variation in genome can influence the individual’s response to particular nutrients and the physiological outcomes
Define nutritional epigenetics
Nutritional epigenetics is a molecular science which examines the way gene expression is changed in ways OTHER than changes in amino acid sequence
Gene-environment interaction
What is a SNP and explain an example
A ‘snip’ is a Single Nucleotide Polymorphism in which a single base is difference in a dna sequence which sometimes results in a structural difference in protein
The FTO gene is an example of a SNP. FTO codes for a specific enzyme on chromosome 16. Increases in FTO expression are associated with poor regulation of energy intake
Explain why lactase persistence is an example of nutrigenetics
In lactase persistence there is a mutation on the enhancer site which increases binding of an activator called Oct1
Oct1 attracts more promotors to the lactase gene throughout the person’s adult life
This prevents the natural decrease in transcription of lactase gene that would normally happen
So steady levels of lactase are continuously produced so ability to digest lactose is maintained
What is transcriptomics?
The study of the transcriptome, but in particular measuring the levels of a particular mRNA that you are targeting
What is proteomics?
A measurement of the levels of a particular protein made in the cell
What is metabolomics?
A measurement of the metabolites resulting from the function of a particular protein
Explain how Nrf2 is a target in nutrigenomics
Nrf2 is a transcription factor which when activated will promote expression of phase 2 detoxification enzymes and antioxidants
Nrf2 is kept in the cytosol bound in the Keap1 complex via disulphide bonds which are sensitive to changes in ROS/RNS
When ROS levels elevate in the cell Nrf2 splits from Keap1 and moves into nucleus and binds to DNA
Particular bioactive food constituents such as curcumin and carotenoids can help in the separation of Nrf2 from the Keap1 complex
Explain the NFkB pathway
NFkB is a transcription factor which regulates inflammatory responses in the cell
Large amounts of ROS, cytokines, AGEs or trans-fats activate the NFkB pathway
When activated the IKKb complex is phosphorylated and NFkB is free to travel to nucleus. Here it binds with IREThis promotes pro-inflammatory genes such as IL-6 and TNF-a
These bind to cytokine receptors and so more cytokines released, creating positive feedback loop
Activation of NFkB pathway blocks the Nrf2 pathway
Explain PUFA signalling
PUFAs modulate the activity of PPARS
PPARS = Peroxisome Proliferator Activated Receptor (alpha, beta, gamma and delta) which act as transcription factors
EPA and DHA are strong PPAR ligands and bind to PPAR response element on cell surface
Different PPARs have diff locations and effects when activated
What are the roles of PPARs?
- Suppress hepatic gene expression of enzymes involved in lipogensis
- increase expression of enzymes involved in beta oxidation
- mediates hepatic apolipoprotein synthesis and cholesterol profile
- downregulates pro-inflammatory gene expression (cytokines)
Where is PPAR alpha and what does it do upon activation?
Mainly found in liver and skeletal muscle
When activated stimulates beta oxidation of fatty acids and decreases levels of cytokines
Where is PPAR beta/delta and what do they do upon activation?
Expression is ubiquitous but lots in GIT
When activated are responsible for insulin sensitivity and glucose homeostasis. Increases glucose uptake and glycogen synthesis. Decrease cytokines and NFkB.
Where is PPAR gamma and what does it do upon activation
Expressed in adipose tissue (white and brown)
When activated it is responsible for maturation and differentiation of adipocytes
