Drugs in Sport Flashcards
What is biological variability?
The natural variability in a lab parameter due to physiologic differences among subjects and within the same subject over time
Do specific genotypes provide athletic advantage?
Yes
165 autosomal gene entries and QTL had an affect on athletic perfomance
What is the importance of athletic performance and whether they provide an athletic advantage?
- Matching genotypes with most effective exercise regimes
- Identifying athletic potential
- Gene transfer technology
What is gene transfer technology?
Take a gene that we identify as being important for a certain condition and dope someone with that genes and hope that the protein increases their athletic performance
What are some indiviual genes that may or may not influence athletic performace?
- Angiotensin converting enzyme (ACE)
2. Insulin-like growth factor 1 (IGF-1)
What does ACE do?
Normally expressed on the endothelium on lungs and kidneys
Liver -> angiotensinogen -> angiotensin I -> angiotensin II
Kidney releases renin
ACE converts angiotensin I into angiotensin II
Breaks down bradykinin
What does angiotensin II do?
It is a potent vasoconstrictor
How does the control of vascular tone have the impact on athletic performance?
In exercise you dilate the vascular bed supplying the muscle and that is key to delivery oxygen and nutrients to allow respiration and key to removing CO2 to stop the build up of lactic acid
What are the polymorphisms for ACE?
Insertion or Deletion 287bp
Determines the amount of ACE that gets expressed
If base pairs are present or inserted, you get?
Lower levels of expression of ACE
Has an increased freqeuncy of elite distance runners, rowers, cyclists
Leads to DECREASED levels of angiotensin II which leads to INCREASED levels of bradykinin which leads to improved vasodilation and substrate metabolism
If base pairs are missing or deleted, you get?
Higher levels of ACE
Has an INCREASED frequency of athletes that are doing short distance events
Leads to INCREASED angiotensin II which increases factors for muscle growth which causes muscle hypertrophy
What is IGF1?
- Similar structure to insulin
- Produced by the liver
- Production stimulated by growth hormone
- Acts through IGF-1 receptor (plasma membrane receptor tyrosine kinase)
- Linked to neurons (neurotrophic factor) exercise induced neurogenesis links body fitness with brain fitness
What are the cellular responses to IGF1?
Involved in the activation of pathways related to:
- protein synthesis
- growth
- proliferation
- metabolism
- survival
How is IGF1 released?
- Through good nutrition and insulin
- Growth hormone in the pituitary gland
- Exercise stimulates the release of growth hormone which stimulates the release of IGF1 which can cause protein synthesis and growth
What does ACE usually do?
Convert angiotensin I to angiotensin II
Angiotensin II is a potent?
Vasoconstrictor
Insulin-like growth factor 1 acts through which type of receptor?
Plasma membrane receptor tyrosine kinase
Insulin-like growth factor 1 stimulates?
Muscle hypertrophy
How does exercise affect genes & transcription?
Exercise induces gene expression changes underlying structural and metabolic adaptations
IGF1 causes muscle hypertrophy
What is epigenetics?
Genetic control by factors other than an individuals DNA sequence
What are 3 things that are alterations in gene silencing?
- DNA methylation
- Histone modification
- RNA-associated silencing
What is DNA methylation?
Addition of methyl group to cytosine
Regulates transcription
Can be passed on (mitotically stable)
How do we control transcription by DNA methylation?
By causing gene inactivation due to transcription machinery is blocked to engage with promoter region and read the particular gene