MT1 Flashcards
0
Q
What is an athlete’s phenotype determined by
A
- Their genes (can’t change)
- How much of each gene is made into RNA
- How much of each RNA is made into protein
- How active the protein is
- -> can change 2-4
1
Q
What is phenotype
A
Genotype and environment (what you see)
2
Q
How do you get from DNA to protein?
A
Transcribe DNA to hnRNA, then process hnRNA to mRNA
Translate mRNA to a nascent protein
Post translational modification of a nascent protein to an active protein
3
Q
What is translation
A
mRNA to protein
4
Q
What is transcription
A
DNA to mRNA
5
Q
What is a SNP
A
Single nucleotide polymorphism
= variation of the sequence of a gene by one base pair
6
Q
If you change your DNA you change your ?
A
Performance
7
Q
What is DNA
A
- Two strands of genetic code
- Made up of sugars and phosphates (backbone) and nucleotides or bases (rings of the ladder)
- The 4 bases in DNA are
- cytosine (C)
- guanine (G)
- adenine (A)
- thymine (T)
- The bases compliments each other such that A binds to T and C to G
8
Q
What is the human genome
A
- Contains ~3.1467 billion base pairs
- This DNA is stored into 23 chromosome pairs
- These 23 chromosomes contain approximately 24000 genes
- These 24000 genes encode for between 300000 to 2 million proteins
9
Q
What are chromosomes made up of
A
Genes
10
Q
DNA packaging affects what?
A
Gene expression
- a more “open” DNA is easier to make more DNA of
11
Q
What are the two types of gene sequences
A
Exons
Introns
12
Q
Exons
A
Made into mRNA
EXons are EXpressed
13
Q
Introns
A
Are spliced out; important for stability and protein make up
14
Q
Promoter
A
Tells is how much, when, and where to make the mRNA
15
Q
What is a nascent protein
A
An inactive protein, does nothing
16
Q
What is epigenetics
A
Lifestyle and environment - how your environment affects your genes
17
Q
How does epigenetics affect our genetic code
A
While our DNA code in our genes does not change, our lifestyle and environment can affect how our genes are expressed
18
Q
How is DNA expression controlled
A
By DNA methylation and acetylation
19
Q
Epigenome
A
Which genes are made into RNA
20
Q
What can epigenetics help explain
A
- lasts longer than the training effect
- “muscle memory”= someone who has trained in the past gains muscle mass and/or endurance faster than someone who hasn’t
- some of the effects of living/running at altitude
- altered epigenetics could explain why taking PEDs at one point might improve training/performance much later in life, after the direct effect (and detection) of the drug is long gone
21
Q
General function of insulin receptor
A
Moves things to membrane
Or
Scaffolding/docking protein
22
Q
General function of S6K1
A
Protein kinase
23
Q
General function of Raptor
A
Identifies substrates
24
General function PI3K
Lipid kinase
25
General function of mTOR
Protein kinase
26
General function of PIP3
Moves things to membrane
27
General function Vps34
Moves membranes
Or
Lipid kinase
28
General function of Rag A
Moves things to membrane
29
General function mSIN1
Moves things to membrane
30
General function Notch
Change transcription
31
General function Rictor
Identifies substrates
32
State the overload principle
Strength gains occur with systematic and progressive resistance of sufficient frequency, intensity and duration to cause adaptation
33
In general, how does "epigenetics" decrease expression of a gene?
1. As we change our environment (training, PEDs, etc) this can change our Epigenome (which genes are made into mRNA)
2. This is controlled by DNA methylation and acetylation
3. To decrease expression of the gene epigenetically we would close the DNA around a specific promoter by altering the degree if methylation/acetylation
34
What are the ways that we can decrease transcription of a gene?
1. Close the chromatin by demethylating/acetylating DNA
2. Make less of an activator or more of a repress or
3. Make less of a co-activator
4. Decrease the activity of an activator
5. Increase the activity of a repressor
6. Move an activator out of the nucleus or move a repressor in the nucleus
35
Briefly, how do amino acids increase mTORC1 activity?
1. Amino acids enter the cell through an AA transporter
2. The increase in aa in the cell causes Rag A/B to bind to GTP and activates Vps34
3. Rag A/B boun pd to GTP is active, binds to raptor and moves mTOR to Rheb (Rab7 positive membranes)
4. When together with Rheb, mTOR becomes activated and phosphoralates S6K1 and 4EBP
5. Active Vps34 causes the Rab7 positive membrane to move around more
6. This increases the likelihood of mTOR interacting with Rheb, activating mTOR
36
Why does IGF-1 gene expression in muscle cause muscle growth when increasing circulating IGF-1 does not?
1. Over-expressing IGF-1 in muscle increases the amount of IGF-1 in a muscle 47 fold without changing IGF1-1 in the muscle
2. Increasing circulating IGF-1 by taking growth hormone results in only a 4 fold increase
3. Over expressing the gene also keeps IGF-1 high 24 hours/day
4. With continuously high IGF-1 levels there is continuously high mTORC1 activity, whereas a transient increase has little effect in mTORC1
37
In elite athletes, what is the best predictor of endurance performance? How would you measure it?
1. In elite athletes, the best predictor of endurance performance is power/velocity at lactate threshold
2. This is measured by performing a graded exercise test while measuring blood lactate
3. Power/velocity at lactate threshold is the power/velocity when lactate begins to accumulate at greater than linear rates with increased intensity
38
Will AAS increase muscle mass?
Yes they will
39
How do AAS increase muscle mass
1. Increase protein synthesis
- mechanism at this point is unknown, but AAS do result in an increase in mTORC1 activity
2. Decreased protein degradation
- competitive inhibitor of the cortisol receptor
- by decreasing cortisol binding of the receptor this results in a decrease in atrogenes and other genes that induce muscle breakdown
40
What precautions do you give a male athlete considering taking AAS
1. Using steroids will decrease the length of your career due to injury
2. AAS will increase aggression. This is good for batting (increases reaction time) but bad in day to day life
41
Why is taking AAS bad
1. While the steroids have a positive effect on muscle mass and strength, they have a negative effect on connective tissue
2. The result is that the incidence of significant injury is much greater than someone who does not use steroids
3. Ethics/getting caught
42
What is transcription
The conversion of genetic code of a gene from DNA into RNA
| - going from storage form of the code to functional form
43
What is an enhancer
Binds proteins to enhance transcription
44
What is a silencer
Binds proteins to repress transcription
45
What is the promoter
The region of the DNA that signals how much RNA will be made from the gene
46
What are transcription factors q
Protein factors that bind to DNA and change the rate of transcription
47
What are co activators
Protein that do not bind DNA, but adjust the activity of transcription factors
48
What is RNA degradation controlled by
1. Processing
- capping
- polyadenylation
- splicing
2. Modulating RNA stability
3. MicroRNA
49
What is initiation
The small ribosomal subunit binds to the mRNA cap and then scans to find the start site. At the start site, it is joined by the big subunit to make the ribosome. Translation begins.
50
What is elongation
The ribosome translates th RNA code into an amino acid sequence (protein). Fr every 3 pieces of RNA (codon) a specific amino acid is added to the end of the protein chain
51
What is termination
The ribosome reaches a stop codon and the protein is released
52
How does mTORC1 regulate initiation of translation
It phosphoralates 4EBP and S6K1
53
What are post transcriptional modifications
1. Phosphorylation/de phosphorylation
2. Acetylation/ de
3. Ubiquitination
4. Oxidation/reduction
5. Ligand/nucleotide binding
54
What is Ubiquitination
It target a a protein for degradation, it acts like a tag marking the protein to be degraded.
55
What causes hypertrophy
Load
56
What are the three aspects of strength
1. Size
2. Neural components
3. Connective tissue
57
What does IRS1 bring to the membrane
PI3Kinase
58
What is PI3K target?
PIP2, makes it into PIP3
59
What does pip3 bring to the surface
PDK1
| PKB
60
What does PDK1 do
Phosphoralates pkb
61
What does PKB do. How does it get activated
When it is phosphoralated by both PDK1 and mTORC2 then it can inhibit the inhibitors
- phosphorylates and inhibits TSC1/2 complex
- phosphorylates and removed PRAS40 from mTORC1
62
What does growth hormone do
It has NO DIRECT effect on muscle size and strength
- it actually increases the amount of water you hold in your body, so your muscles appear bigger
- it does improve your ability to recover
63
Briefly, how does the resistance exercise pathway work
By some unknown mechanism, resistance reservist phosphorylates TSC1/2 complex and moves it away from the lysosomes
- when it moves away, Rheb is now GTP bound and can activate mTORC1
64
How is the majority of force transferred
Laterally
65
What do actin and myosin do
They create force, but do not produce tension
66
What are mechanoreceptors? What are their function with mTOR?
- length sensors (costameric proteins)
- tension sensors (Titin, Muscle Lim protein)
- stretch activated channels
=> an increase in any/all of these lead to TSC1/2 being phosphorylates and mTOR being activated
67
What happens when you lose dystrophin
You get a large decrease in lateral force transmission and more injuries
68
What is testosterones main effect
Blocking glucocorticoids therefore blocking protein breakdown
- testosterone also increases the number of satellite cells
69
What is myostatin. What does it do
A feedback protein that regulates the amount of muscle you have
1. Controls muscle fiber number
- regulates muscle fiber proliferation
2. Controls muscle fiber size
- regulates mTOR activity
- regulates transcription of genes important in growth
70
What does training do with myostatin
It decreases myostatin. mRNA
71
Myostatin pathway summary
Myostatin binds to ALK and ActIIB together, when ALK is bound to myostatin it phosphorylates Smad 2/3. With Smad 2/3 phosphorylated, it can bind to Smad 4. Smad complex enters nucleus and decreases transcription
72
What inhibits myostatin
Ski, sno and notch inhibit the Smad complex in the nucleus
73
GPF5 pathway summary
GPF5 binds to ALK3 and BMPR1 and when bound ALK3 phosphorylates Smad 1/5/8. This can bind to Smad 4 and this Smad complex goes into the nucleus and activates Mighty. Like a protective mechanism, keeps am injured muscle from shinr I making away to nothing
Also, helps set your baseline. Someone with more Smad 1/5/8 will be a bigger individual
74
Smad signaling competition
Whether there is more Smad 2/3 or Smad 1/5/8 determines which Smad that Smad 4 binds to.
75
As you increase exercise intensity which fuel do you primarily use
Sugars, carbs,
76
At lower. Intensity of exercise, which fuel source of you use most
Fat
77
If you have higher sympathetic nervous system activity, which fuel source is used
More sugar
78
How does diet and exercise history dictate fuel use
If in a high fat, low carb diet you have more fat so more likely to breakdown fat as fuel
- more endurance exercise = more mito, so more fat as fuel
79
How does blood flow dictate fuel use
A decrease in blood flow caused by Sns stimulation (vasoconstriction) causes a decease in flow to adipose tissue so less fat used
80
What does epinephrine stimulate for fuel purposes
It similes glycogen phosphatase= breaks down glycogen into glucose
- more flucosw because of epinephrine so a decrease in need for fat
81
Lots of epinephrine stimulate what
Alpha adronergic receptors, causes vasoconstriction, less blood flow to everywhere except muscle because muscle metabolizes override the stimulation and cause local vasodilation
82
How do you calculate Vo2 max
SVmax x HRmax x a-Vo2
| - SV is what we can change to increase our Vo2 max
