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
What happens to the genes that were associated with metabolism?
They had become hypomethylated
What is hypomethlytion and gene expression?
PGC-1a
Regulates genes involved in energy metabolism, mitochondrial biogenesis and function
Regulates fibre type determination
What is PGC-1a?
An integrator of many difference external signals
Regulates protein involved in:
- Mitochondrial biogenesis
- Glucose utilisation
- Fatty acid oxidation
- Antioxidant detoxification
DNA can be methylated on?
Cytosine
DNA methylation does which of the following?
Inhibits gene transcription
In terms of DNA methylation, exercise has been associated with?
Hypomethylation of selected DNA
What is VO2 max?
The maximum volume of oxygen
ml/kg/min
Measure of endurance fitness
Largely determined by genes - can be increased by training
5-20% up to 60% reported but training can make little difference (due to genotype)
What percentage of genetic factors accounted for VO2 max before training?
40%
What did the heritage family study determine?
A greater variability in change in VO2 max between rather than within families
Highlights a genetic component for change in VO2 max
NO relationship between where the VO2 max started and how much it changed by
INITIAL VO2MAX AND CHANGE IN VO2 MAX REGULATED BY DIFFERENT GENES
Which genes showed positive results to allow VO2 max to change massively?
- Muscle creatine kinase (CKM)
- A particular DNA variant was associated with increases VO2 max
What does muscle creatine kinase do?
It regulates ATP supply
What are some genes asscoiated with increasing VO2 max trainability?
- Muscular subsystems
- Electrolytes balance
- Lipid metabolism
- Oxidative phosphorlyation and energy production
- Oxygen delivery
VO2 max is considered an indicator of what?
Maximum volume of oxygen that can be used
How is VO2 max determined?
Is determined by many genes
When was doping banned?
In 1928 by the international amateur athletics association
What are the banned substances set by the world anti-doping code for 2019 to be banned at ALL TIMES?
- Non-approved substances
- Anabolic agents
- Peptide hormones
- Growth factors
- Beta-2 agonists
- Duiretics
What were the methods banned at ALL TIMES by the world anti-doping code 2019?
- Manipulation of blood and blood components
- Chemical and physical manipulation
- Beta blockers
- Gene and cell doping
What substances were banned IN COMPETITION by the world anti-doping agency?
- Stimulants
- Narcotics
- Cannabinoids
- Glucocorticoids
What is the most commonly abused drug in sport?
Anabolic steroids
Why are anabolic steroids used?
They enhance skeletal muscle mass and bone
What is the most common steroid?
Stanazolol (20% of steroids)
Clenbuterol is also commonly used
What are endogenous steroids?
They occur naturally
Testosterone and substances in metabolic pathways
What are exogenous steroids?
Copies of testosterone
How is testosterone found in the bloodstream (3)?
- Strongly bound to sex hormone binding globulin (70%)
- Weakly bound to albumin (30%)
- Unbound (0.5 - 3%)
The world anti-doping agency have banned steroids during?
At all times
Where does testosterone act?
On the androgen receptor
How is the effects of testosterone described?
Androgenic and anabolic
What were the chemical models in testosterone attempting to do?
- Slow inactivation
- Change the pattern of metabolism
- Increase lipid solubility (injection and slow release)
What do athletes primarily want from changing the chemistry of testosterone?
Increase anabolic: androgenic ratio
What is the mechanism through which testosterone causes its anabolic effects?
Activation and dimerisation of androgen receptors, allowing their translocation to the nucleus to regulate the transcriptional machinery
How is the anabolic activity of steroids changed in the molecule?
In the cyclohexane rings
What are the 3 morphometric changes on the effect of testosterone administration on muscle?
- Increased muscle volume
- Quads and vastus lateralis increased by 14% - Increased cross-sectional area of type 1 and type 2 fibres
- No difference in proportions
- Type 1 = increase of 48%
- Type 2 = increase of 36% - Increased myonuclear number
- More training = more nuclei fibres
What are the morphometric changes associated with?
- Increased protein synthesis
- Reduced amino acid export
- Increased androgen receptor expression
What can fibre hypertrophy lead to?
- Increased strength
- Enhanced Ca2+ release from the sarcoplasmic reticulum
- Changes in Ca2+ sensitivity of contractile proteins
- Changes in muscle structure
What is pennation?
Pennate muscle fascicles attach in a slanting position to the tendons - allow higher force but smaller range of motion
CANNOT CHANGE MUSCLE STRUCTURE BY STEROIDS
What describes the effects of anabolic steroids on muscle?
- Increased pennation
- Fibre hypertrophy
- Increased myonuclear number
- Enhanced calcium release or senstivity
