Week 7: Molecular basis for adaptation to exercise Flashcards

1
Q

Molecular basis for adaptation to exercise

What theories did the follow people determine?
- Charles Darwin
- Gregor Mendel
- Friedrich Miescher
- Barbara McClintock

A

Charles Darwin

*Developed the theory of evolution based upon observations of natural selection
* Observed distribution & continuation of animal & plant phenotype in response to their environment – “Survival of the fittest”
* Theory explained adaptive modifications in response to environmental stressors for preservation of species

Gregor Mendel
* Discovered hereditary characteristics of plants and effect of genetics on traits
* Through selective breeding and monitoring developed over 10,000 varieties of pea plants
* Identified dominant and recessive genotypes and how these determine phenotype

Friedrich Miescher (1844-1896) & Phoebus Levene (1869-1940)
* Miescher was first to identify DNA, extracting nuclei from white blood cells
* Levene conducted important work on the nucleic acids, the building blocks of DNA
* Findings helped pave the way toward our understanding of DNA and RNA as the key elements in the maintenance of life

Barbara McClintock (1902-1992)
* Discovered so-called “jumping genes” or the phenomenon of genetic transposition within the genome
* Showed how certain genes were responsible for turning on and off physical characteristics
* Developed early theories of epigenetics – the suppression of expression of genetic information in response to various stimuli/stress

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2
Q

What theories did the follow people determine?

Rita Levi-Montaclini
* Discovered and characterised nerve growth factor
* Identified its importance in the development/maintenance of the nervous & immune system & role in stress management
* Critical work contributed to our understanding of the role of nerve growth factor in cancers, tumours and the brain in health & disease

Rosalind Franklin
* Co-discovered the double-helix structure of DNA, forming basis for modern biotechnology
* Franklin obtained images of DNA using x-ray crystallography, an idea defined by Wilkins
* Watson & Crick used images and available evidence to theorise the nucleotide base scaffold and how genetic information is transferred in living material

A

Rita Levi-Montalcini (1909-2012)
* Discovered and characterised nerve growth factor
* Identified its importance in the development/maintenance of the nervous & immune system & role in stress management
* Critical work contributed to our understanding of the role of nerve growth factor in cancers, tumours and the brain in health & disease

Rosalind Franklin (1920-1958), Maurice Wilkins (1916-2004), James Watson (1928-) & Francis Crick (1916-2014)
* Co-discovered the double-helix structure of DNA, forming basis for modern biotechnology
* Franklin obtained images of DNA using x-ray crystallography, an idea defined by Wilkins
* Watson & Crick used images and available evidence to theorise the nucleotide base scaffold and how genetic information is transferred in living material

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3
Q

Foundations of genetic expression

Basis of molecular biology

Genotype
* The “Genetic blueprint”
* ….. chromosomes pairs inherited from parents
* Genes are segment of DNA with a specific code sequence
* The genome is an individual’s entire genetic sequence containing the full set of …..

Phenotype
* Observation characteristics resulting from the ….. of the genotype
* Also dependent on ….. and …..

A

23
Genes
Expression
Behaviours & environment

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4
Q

What is DNA?

A

DNA structure
* Double helix phosphate-sugar backbone bound by base pairs – the nucleotide
- Adenine = Thymine
- Cytosine = Guanine

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5
Q

What is RNA? How do the base pairs differ to DNA?

A
  • RNA is a single stranded nucleic acid used in replication and protein synthesis
  • Adenine = uracil
  • Cytosine = Guanine
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6
Q

What are codons?

A

Genetic alphabet
* The letters along DNA/RNA strands are deciphered in triplets known as codons
* A codon “codes” for one of the 20 amino acids
* Amino acids are the building blocks of life, stringing together to form proteins

EG CCG = arginine

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7
Q

What is protein synthesis? What are the two phases involved?

A

Protein synthesis
* Two major phases in gene expression and protein synthesis:
- 1. Transcription: creation of complimentary strand of RNA based on DNA template
- 2. Translation – protein synthesis from amino acid chains determined by base sequences transcribed to RNA

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8
Q

How are genes relevant to health and human performance?

A

Health
* Disease prevention
* Healthy aging
* Injury treatment
* Exercise effects
* Diet effects
* Many more….

Human performance
* Predicting performance (Talent ID)
* Athlete trainability
* Doping/performance-enhancing drugs

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9
Q

For your health – Understanding & fighting cancer

  • Molecular biologists have identified the epi-genetic effects of several behavioural, environmental and chemical stressors
  • ….. gene activity helps stop the formation of tumours – ….. activity of this gene increases predisposition to cancer
  • These discoveries aid in the development of …. and ….. measures
A

P53
Inhibited
Cures & preventative

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10
Q

Exercise & protein synthesis - myofibrillar

A

In untrained, myofibrillar fractional synthetic rate increase is stimulus specific.

Trained & untrained individuals have greater myofibrillar FSR at rest and unspecific response to exercise stimulus.

Intracellular signalling mediates the exercise-induced response to resistance and endurance training, leading to specific protein synthesis

In untrained, mitochondrial FSR increase is non-specific to exercise stimulus. Trained individuals have specific mitochondrial FSR response to stimulus - endurance, not resistance exercise.

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11
Q

7.04 – Genetics & athletic potential

Identifying athletic potential – gene expression

Angiotensin converting enzyme (ACE)
* Central component of the ……-…… ….. ….. (RAAS), which controls blood pressure by ….. …… in the body
* Converts ang I to angiotension II – a powerful ……
* Insertion variant more prevalent in ….. athletes – lower ….. levels, permitting higher maximal heart rate and oxygen consumption
* Deletion variation & ACE greater in power athletes

A
  1. Renin-angiotensin aldosterone system
  2. Fluid registration
  3. vasoconstrictor
  4. Endurance
  5. ACE
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12
Q

7.04 – Genetics & athletic potential

  • …… is the primary mediator of the RAAS synthesised in the liver and cleaved by renin to yield ANG-I, which ACE catalyses to ANG-II
  • …. is the rate-limiting steps to ANG-II production
  • The …. allele of the M235T polymorphic site has been correlated with ….. ANG-II levels and therefore increased …. and ….. growth
  • …. allele is more prevalent in endurance athletes
A

Angiotensinogen AGT
Renin
C allele
Greater
BP & muscle growth
T

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13
Q

7.04 – Genetics & athletic potential

  • …… responsible for synthesising the alpha protein which stabilises actin filaments in ….-twitch muscle fibre Z-lines
  • Prevalence of this gene more prevalent in power athletes, with >…..% having atleast one ….. allele
  • ~…..% of the population does not have ACTN3 and may have fewer IIa/x fibres, develop less strength and power and be more susceptible to muscle damage
A

Actinin-3 (ACTN3)
Fast-twitch
>90%
R
~20%

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14
Q

7.04 – Genetics & athletic potential

  • PGC1a is a critical ….. factor protein that is the master metabolic regulator, unregulated by exercise
  • Regulates …. ……, …. …. ….. and B oxidation, gluconeogenesis, brown adipose thermogenesis, …… and fibre type adaptations
A

Transcription
Mitochondrial biogenesis
Fatty acid mobilisation
Angiogenesis

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15
Q

7.04 – Genetics & athletic potential

  • ……. protein synthesis stimulates …… and …… – the formation and adaptation of blood vessels
  • Expression signalled by ……
  • HIF1 master regulator of cellular and systemic homeostatic response to …..
  • Critical protein in ….. adaptations
A

Vascular endothelial growth factor (VEGF)

PGC1a and hypoxia inducible factor 1 (HIF1) after ischemia

Hypoxia

Endurance

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16
Q

Predicting athletic trainability

  • It is possible to predict an athlete’s responsiveness to a particular training stress
  • As discussed, there are many genes or genetic variants that can increase or decrease an individual’s response to a stressor
  • Could lead to more efficient and effective training and adaptations
  • Still more research needed in this area
A
17
Q

What does PGC1a stand for?

A

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1a)