Lecture 1

Topics in exercise physiology

Emmet
Quiz q: identify the functions of the lipoproteins and chylomicrons

- theyre covered topics in many places of the world

- talking about several different functions that are important
- Metabolism: the production of energy from musc contraction and understanding the balance of energy intake v energy
expenditure
- neuromuscular syst
- cardiovascular-respiratory system

Risk Factors for Coronary Heart Disease (CHD)

- CHD is common in North American societies ; there are a number of risk factors assoc w/ heart disease & is very prevalent
- how can exercise help us in modifying either the risk factors or the disease itself?
- they are classified by:
• those that can’t be modified
- heredity; there are genetic factors involved that you cannot really change
- gender; people can change their gender obvi but cannot change the gender theyre born w
- age
- race; can’t be changed
- these are just factors that cannot be modified
•those that can be modified:
- cigarette smoking - obesity
- high serum cholesterol - stress
- high bp - blood glucose
- physical inactivity —> only recently has this made the list of factors that can be modified
- the physical inactivity level is one that is dominant in determining some of the other factors
- ex. If you are very active its likely that your bp is lower, your body weight is more in the regular range, your chol lvl are
lower, generally aren’t a smoker, and blood glucose is more normal

Notes on CHD RF’s *RF=risk factors*

1. Lists of rfs evolve over time as epidemiological evidence has accumulated showing the assoc b/w various conditions and CHD
2. For ex (of #1) its only recently that PA and obesity have become RFs according to the American College of Sports Medicine
(ASCM) and the American Heart Assoc
3. Note that a high fat diet is not on the list of rfs for CHD.
- its already represented by the obesity and cholesterol rfs
- its believed that controlling the type and amount of dietary fat would reduce the risk of CHD
4. Health promotion programs deal directly w/ physical inactivity, diet, and stress to prevent other RFs from occurring. The
primary nonpharm trestment of these rfs revolves around recommendations for a lot fat diet and regular PA
5. The ASCM lists one of the subfractions of cholesterol (high density lipoprotein chol [HDL-C] as an additional rf. The risk of CHD
is lower for those with high concentr of HDL-C (its a - rf when levels exceed 60mg/dl [ie. abt 25% of the total chol])
•This diagram is taken from the textbook
- % of the US population at risk
- bottom shows the rfs and risk ration
- high BP represents 10% of the population , and they have 2.1x more risk to heart disease than
someone w/ reg bp ≥150mmHg
- 10% of the pop has a high serum chol (that’s total chol, thats comprised of subfractions, 2.4x
more risk if you have a high total ≥240mg/dl (25% of this number is 60mg/dl of HDL-C, the
good cholesterol
- cigarettes=18%, so almost 20% of the population smokes and are at 2.5x more risk of heart
disease (1pk a day v no smoking)

- the dominant bar is the physical activity where 59% almost 60% is physically inactive
- physical inactivity has a 1.9 risk ratio

The risk ratio for inactive people during COVID

- the line is for people who were active with COVID
its normalized at 1.
- the risk when being inactive is twice as much (w/ hospitalization, icu admission, and even
death)
fictive - being physically active affects your lungs and improves lung function and makes immune syst
people w/
COVID-19 more robust.

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 Lipoproteins serve to move cholesterol and triglycerides around the body

- when you eat dietary fat, it comes into the gut

- fats are insoluble since theyre lipids so they dont mix w/ blood
- to transport lipids from the blood you need a carrier to transport the lipid
- theres a lipid protein thats like a droplet? That has the lipid inside of it and the protein solubolizes
the fat thus allowing it to transport it in a way that is effective in a aqueous solution (basically since its
inside the protein it can move thru the water)

- when you take in dietary fat, its absorbed by the epi cells in the gut and taken in the blood and forms a Chylomicron which is the
very lowest density particle
- a Chylomicron is 98% lipid, 2% protein
- contains high amounts of triglycerides
- the big fat droplet travels from the gut to the liver for the liver to metabolize
- the liver changes some of the triglycerides to cholesterol and repackages the triglycerides
and chol into particles that are smaller that come from the liver as Very Low Density
Lipoproteins [VLDL] or Low Density Lipoproteins [LDL]
- from the liver these (VLDL,LDL) transport primarily:
- VLDL: transports 92% lipid, 8% protein, thus more dense than the Chylomicron but doesn’t
has less amounts of trigly than the Chylomicron
- LDL transp high amounts of cholesterol > than the VLDL and is the primary deliverer of cholesterol; it has 80% lipid 20%
protein, its more dense
- density increases as you increase the amount of protein
- so the liver takes the VLDL and LDL to the tissues into the blood vessels and deposits chol and trygl into these areas
- cholesterol is deposited onto the lining of blood vessels and forms plaque which over the course of years and years calcifies
and solidifies, the hardening of it can eventually lead to a blockage of the blood vessel [this is an age depended phenomenon]
- theres a syst that takes the cholesterol AWAY from the BV —> High Density Lipoprotein [HDL]
- HDL is also made in the liver but serves to remove cholesterol from the blood vessels and deliver it back to the liver where it is
metabolized
- HDL has the highest density due to it having the highest amt of protein - 50% prot and 50% lip; it has a lot of cholesterol since
its removing it from the BVs a

- all of this (VLDL LDL HDL) makes up total chol —> total chol should be less than 240mg/dl w/ 25% or more as HDL-C
- the higher it is the greater the RF, but the higher the HDL the better since its a NEG RF;
- physical activity increases the level of HDL
- training decreases the amount of VLDL and LDL
- the density is found through blood sample, the blood sample is taken and put into a centrifuge

- the highest density stuff goes to the bottom and the lowest density floats at the top

Self-Reported Leisure-Time Physical Inactivity in Canadians (>12 years old)

- this is from epidemiology studies, the national average of inactivity is about 55%

- there are regional differences across the country

- provinces that are most inactive are: New Brunswick, PEI, Manitoba, NFL, Sask, Quebec, and
Ontario
"
Ko
,

Northwest
"
"
"

- in the west: most inactive = MB; most active = BC

Territories %4✗
Bc
"

- in the east: most inactive = NB; most active = NS

Alberta
Nf, %
Sask
Quebec
Mohit .

Ohta, , PEI - Ontario is central; and is about the national average

Ns
New
Brunswick

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Development of Research Interests in Exercise Physiology
•1900-1960s - Beginnings
- muscle physiology and fatigue, lactic acid as a poison,
- in the 1920s, there was the the discovery of ATP and PCr,
- musc metab was measured as heat prod
- exercise physio began w/ the study of amphibian musc
•1960s-1980s - Focus on Sports and Athletics
- the development of the muscle biopsy technique - taking a portion of musc using needle and testing the musc for different
metabolites like gylcogen; studying the types of fibers, and even looking at atp
- also looking at how the heart and lung responded to exercise
•1980s-1990s - Medical Awakening
- people thought about the application of fitness to workplace, cardiac rehab, and etc
- HDL -C was discovered
- employee fitness plans began to develop & cardiac rehab programs were seen to be important
•1990s-Present - Exercise and Health; Molecular Mechanisms
- there are more advanced molecular techniques to study the molecular mechanics, changes in gene expression in response to
exercise and disease at the heart and muscle level
- the exercise in relation to health is vital for people to understand
- lack of exercise as an RF became on the list
- exercise for special populations is a growing field all the time

- in the past, exercise physiology was studied uniquely in PE programs

- now exercise physiology is part of many different programs now

Anatomy of ATP: Made of 3 parts

(Adenosine TriPhosphate)
- Adeinine
- Ribose
- 3 Phosphates - theyre held together by high energy bonds, when you break the bond you
release energy
I

End of lecture
 Lecture 2 - sept 13
Quiz: 1. How does LDL differ from HDL
2. What makes CPK a special enzyme
3. Use words to describe the E-C coupling processes in muscle

ATP-PC System of Energy

- when theres no phosphate and all you have is ribose and

adenine, the molecule is called adenosine The structure of ATP
- we’re going to talk about the cycle of ADP + Pi -> ATP

- when the reaction takes place and 7 kcal energy is lost you
are left with ADP+Pi (the energy bond was broken off for
work function)

- there are many ATPase in the cell ; the most famous ATPase is Na/K ATPase pump
- there are others such as MyosinATPase, CaATPase
- all ATPase systs do the same thing, they break atp > adp +pi and in the process use the energy to do something (ie. pump Na,
pump Ca, etc etc)
- ATP is the currency of the cell, it needs to be regenerated, metabolism does that
- energy metabolism (catabolism) provides energy to synthesize ATP
- ex. Breaking down glucose, fats, all regenerate ATP
- As soon as you lose energy the cell dies so you need to replenish it ASAP since many functions in the cell use it
- ATPases = class of enzy that breakdown ATP to provide useful cellular energy
- ase = enzy
- to maintain ATP at a high rt of energy expenditure, there are 3 systems that are activated
1. ATP-PC - rapid & one reaction
2. Anaerobic Glycolysis - intermediate
3. Aerobic - long term

What Happens During the first seconds of exercise?

-ex. Getting up out of a chair
- theres an energy demand to the getting up from a chair and walking
2- energy demand increases, and then stays constant for the period of time
you are walking, when you stop energy demand is back down to rest
3
£

1. 3 (baseline)
- we have to cover that energy demand w some supply —> we incr the
demand of ATP by getting up and walking for a period of time then sitting
down
- Scenario 2: theres a sprinter, when the gun goes off and he begins to
sprint, the demand is much higher than walking (intensity is high) ; the
demand stays relatively constant, then when he finishes the demand comes
back down again

-the height of the demand depends on the height of intensity and how long you’re doing it assuming you dont change pace
-the demand needs to be met ; hence why theres 3 systs
-theres a syst thats activated right away
-initially, the immediate coverage of energy is from the ATP-PCr system, it covers the initial seconds of energy used
-the other 2 systs will eventually ramp up and cover the remainder of the period
-theres some ATP in the cell that can be used right away but it runs out quickly
-the other reactions take long because of multi-enzyme pathway “sluggishness”
-so syst 1. Uses ATP > ADP + Pi and generates 7 cals and the cals is going to be used to gen the myosin-actin bridge
-what activates myosin ATPase?
- starts at the brain and travels down to the nervous system and motor neurons and activates the musc to contract and that is
called excitation contraction coupling

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During exercise:
- Ca activates myosin ATPase INDIRECTLY then we get the breakdown of ATP into ADPf (f=free) + Pi
- ADPf is gonna take part in a rxn w/ phosphocreatine
- they’re combine by Creatine Phosphokinase CPK and converted into Creatine + ATP
- Phosphocreatine (PCr) has a high energy bond thats bound to creatine, so what the enzy in CPK does is its cleaving the
phosphate off and adding it to the ADP thus regenerating ATP again really quickly
- when you take the phosphate off of the PCr youre left w just Creatine
- We only have a lil bit of ATP in the musc, only enough for a few cntrcns
- its quite likely that atp will remain constant as exercise is happening in the first few seconds
- PCr will go down in concentration and creatine concentr will go up [Cr = creatine]
- PCr is basically sacrificing itself to maintain ATP levels
Suppose the exercise is over:
- we need to restore things back to normal
- once you stop the exercise youre recovering from the exercise

- once you stop exercising, theres no more Ca activating the myosin ATPase (cause theres no more APs) ; so myosin ATPase isnt
activated anymore so theres no more ATP being broken down
- this allows other systems of energy of production (ie. the aerobic syst)
- the atp from the mitochondria + the high Cr that was built up drives the CPK rxn the other way, thus creating PCr
- PCr goes back up to its normal resting levels after being depleted
- CPK is an equilibrium enzyme (it can go in both directions)

Muscle Structure - Quick Review

- muscles develops from myoblasts
- muscles are very long fibres
- theyre really long cells as compared to neurons
- muscle cells develop from single celled myoblasts into multi-uncleared myotubes during development

- long multinucleated mature muscle cells = muscle fibers (called myofibers)

- single fibers contain myofibrils and also are surrounded by resident satellite cells
- the satellite cells have one nucleus and contribute to the reparation and generation of muscle when injured
- A single sarcomere is the contractile unit of the muscle fiber in a myofibril
- myofibrils have striations
- thin filament consist of actin ; thick filaments cont myosin
- during contractions the Z lines come closer together; the sarcomere shortens —> thats how we get the shortening of the muscle

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 voltage sensitive
Review of Excitation-Contraction Coupling in SKM

:
- when you begin to exercise the motor cortex sense
messages down the spinal cord thru neurons to synapse w/
motor neurons in the spinal cord that extend out towards
the muscles — cortex sends APs to the alpha motor neurons
- AP triggers the release and fusion of vesicles w/ the
terminal endings of the neuron and those vesicles release
ACh
- ACh diffuses across the synaptic cleft at the neuromuscular
junction (a specific pt in the musc memb)
- ACh crosses and binds to an ACh receptor
- when ACh binds to that receptor, it causes the opening of
the channel and Na comes in and diffuses across the mem
in both directions and that Na activates other channels for
Na
- its a receptor operated Na channel (green) b/c it binds
the neurotransmitter (ACh)
- there are voltage sensitive Na channels (blue box) that
respond to changes in Na on the inside of the membrane
[making the inside a lil more positive] - they respond to a
change in voltage
- remember that in a musc cell theres a negative RMP
(-80, -75mv) when Na comes in it changes it to a more
positive value and thats what these voltage sensitive Na
channels respond to
- the Na channels open and Na rushes in thru ; this happens
all along the membrane and down the t-tubule of the muscle
cell
- the voltage change along the t-tubule activates 2 protuends that interact
- b/w the t tubule and the SR
- the SR *sarcoplasmic reticulum* is like a bag of calcium ; it has a very high concentr of ca
inside
- when the AP travels down the membrane and gets inside to the black dot
- this symbolizes the interaction b/w 2 proteins
- one is a voltage sensor in the t-tubule membrane and thats called Dihydropyridine DHP receptor and it interacts w/ the
Ryanodine receptor (which is also called the Ca release channel since its on the inside of the SR)
- when the AP travels down it changes the conformation of these proteins (their shapes) and the result is the opening of the
Ryanodine receptor and Ca is released into the cytoplasm
- when ca is released it travels down to interact w/ the thin filament proteins (the yellow = troponin)
- thin filament of actin is the green
- in the absence of Ca tropomyosin sits on thin filament of actin and blocks the interaction of actin and myosin
- this is the myosin crossbridge
- when Ca comes and binds to troponin, the tropomyosin moves out of the way and allows actin and myosin to interact
- at the same time, the enzy at the head of the myosin is activated and that enzy is myosin ATPase
- that breaks down ATP -> ADP + Pi and the energy is used so that the crossbrisge can attach and rotate and when it rotates
the sarcomere shortens
- when theres no more AP, theres no more Na coming in so then theres no more Ca is being released , Ca is taken up back into
the bag of ca storage (SR) and then now the musc can relax since the tropomyosin blocks the binding site w/ actin and now actin
and myosin can’t interact

End of lecture
 Lecture 3 - Sept 15th 2021

Quiz:
1. What drives CPK in 1 direction or another
2. What does the Ryanodine receptor do?
Review of Excitation-Contraction Coupling
- ach release binding to receptor which is a receptor operated Na channel ; Na comes in and diffuses and activated voltage gated
Na channels —> Na comes in and the propagation goes down the t-tubule and then activates the voltage sensor thats in the tutble
(DHP and Ryan receptor) —> causes conformation change, opens Ca channel and Ca travels to troponin and causes a conform
change there and alts the function of the prot (tropo moves out actin and myosin’s way) and now myosin ATPase is broken down ,
ATP is used to rotate and shorten the sarcomere
- when AP stops Ca is taken back up into SR —>
*if confusing look at last page or KINE 2011 notes*
- K+ being released brings the membrane potential down back to RMP (≈ -80mV)
- in the cytoplasm theres the CPK rxn taking place, there are glycolytic enzys taking
place
- myosin is a dimmer (2 chains of 2 proteins together) —> the head of the myosin mols
has the ATPase enz in it
- all the action is in the head
- MyATPase is also called the Myosin heavy chain isoform
*MyATPase = MyosinATPase*
- Many proteins have isoforms (ice cream analogy?)
- isoforms determine the fibre types

*review*- During exercise: PCr is used up, Cr is produced, and ATP

maintained using the regenerating syst
- During recovery when theres no AP: MyATPase isnt activated, so no
breakdown of ATP->ADP, mito replenishes the ATP, Cr is reversed back
into PCr

Facts abt ATP & PCr

1. ATP & PCr r in the cytoplasm and are avail for immediate use
- its gonna buffer any changes in ATP thru the immediate MyATPase
rxn
2. [PCr] is 20 µmoles/g while [ATP] is abt 6 µmoles/g (so abt 3-4x less)
3. PCr is used rapidly and restored while ATP stays relatively constant
even during high intensity exercise (PCr donates its P to maintain ATP
during exercise)
4. PCr utiliz depends on the exercise intensity
{refer to graph on right side for 3. & 4.}
- at rest PCr is at 100%
- in order to measure PCr you have to take a sample of muscle from the
subject (usually taken from vastus lateralis)
- at mild intensity of exercise: PCr drops and then wont be used anymore (pink line)
- w/in the first min youre using about 30% of the PCr
- when you use a sufficient amt it plateaus —> the other systs kick in so you dont need to use it anymore
- when you start to exercise all three systs begin but 2 of them are slower
- @ moderate exercise: PCr drops even more to abt 50% since the energy demand is higher (green line) ‘
- if the energy demand is higher youll use more PCr
- will still plateau once the other 2 systems kick in
- we never 0 out PCr (red line)
- when you stop:
- PCr goes up and recovers very quickly
- normal levels of PCr recover by 90% in 2 mins
- The ATP-PC syst is important for all exercise types and intensities. It is particularly important for events req a higher power output.
It is rapidly avail, but not plentiful
5. PCr restoration depends on blood flow -> O2 delivery -> aerobic ATP production from mitochond during recovery from exercise
- What drives the recovery pt:
- ppl in Scandinavia did an experiment where they asked ppl to do exercise bouts and in some of the people, they wanted to
see what impact the aerobic syst had on the recovery of PCr so what they did was they did the mild mod sev exercise then had
them recover normally, then they saw the pattern
- they asked them to come again but this time they put a BP cuff on the musc being worked (thigh area since its on the
bike)and that caused occlusion of the blood vessels thus stopping the blood flow
- they found that PCr didn’t recover (the dash lines of the chart) —-> there was no recovery until they removed the bp
cuffs off and then blood flow could be restored —> point 5.

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The ATP-PC system is important at the start of exercise:
• Evidence: genetically deficient mice (“knockout” animals) w/o the CPK gene show a decr in musc performance at the start of
musc contractile activity
- a knockout animal is an animal thats engineered to be missing or having a mutation in
one gene
- molecular biologists developed these mice models that had one gene missing
- they knocked out the CPK gene in this experiment
- in a normal animal:
- you get a tiny bit of fatigue if they dont make the musc cntr too hard (green)
- in a CPK knockout animal:
- initially you see a rapid drop in force output (w/in the first min)

- force drops due to early on fatigue and then the force generally will plateau since theres no real issues w/ the other 2 systems
(red)
- so you need the early syst for energy prod basically
*the opposite of a knockout animal is a transgenic animal
- the molecular biologists insert more copies of a gene into the genome of a mouse —> makes much more prot compared to a
normal wild mouse*
What are the benefits of Creatine Supplements?
1. Original studies used 5G taken 4x/day * 3-5 days
- this is a lrg dose, equiv to 4kg fish or steak/day
- Creatine is stored in musc tissues
2. They have no known side-effects, yet, when taken for months ar a more reasonable dose of 3g/day
3. Can incr PCr by 5-15% (variable, depending on the normal diet of the consume)
4. May have muscle and other health benefits, esp in older adults
- people w/ musc weakness or a neuromuscular disease
5. Creatine is an AA analogue, which is important for its transport. It also has osmotic effects on the cell
Explanation:
- when you absorb a bolus of Cr, the concentr of it goes up in the blood, and then it is
transported into the musc cell
- the musc stores Cr
- you get so much Cr inside the musc that the concentr of Cr draws water into the musc cell at
the same time to equilibrate the concentr of Cr across the membrane into the musc cell =
Osmosis
- when water follows Cr, the musc now retains the water so then the musc cell begins to swell
(the pump)
- Cr gets into the cell using a transporter to get inside the plasma membrane since the membrane
is selective
- Glucose transporter is one of the most “famous” transporters in the muscle
- when you ingest glucose, blood glu lvls incr —> tissues start to accumulate gluc via an insulin
mediator ; insulin is released from the pancreas when blood gluc is incr —> insul circulates in the
blood and binds to a receptor on cells —> when it binds to a receptor it triggers steps that lead to
the activation of a glucose transporter on the membrane —> glucose is taken up into the cell
- insulin acts on the glut4 transporter and also affects AA metabolism as well
- so when insulin incr it also activates an AA transporter => so since Cr is a structure of 2 AA, it
allows for Cr to bind to the transporter and stimulate its transport into the muscle as well
- when you take a Cr supplement, take a lil gluc with it to maximize uptake into the muscle

8. PCr utilization and restoration improves w/ Cr ingestion

- when you take the Cr supplement: you’re already starting at a higher level so when it depletes it
wont go as far down
- => the recovery is considerably faster, theres a faster rt of recovery (ie. most of it back in like 1
min)

end of lecture
 Lecture 4 - Sept 17 2021

Quiz:
1. What is the Vmax related to the cell?
2. Explain how glucose ingestion helps to accumulate Cr in the muscle

*review the last lecture*

9. Performance improves in some studies:

- 30 sec max cycling - work improved 4%
- intervals (300 or 1000m sprints) — better times in the final (4th) interval
- Max knee extensions (30 reps x 5 bouts) — better performance in bouts 2,3,4
- if you increase your work output during training as a result of Cr ingestion, then this could improve your performance (this is an
indirect effect)
- due to sparing PCr during exercise + better resynthesis during recovery

Should creatine be a banned substance?

=> Cr is linked to better performance in high intensity events
Carbs is linked to better performance in long distance events .. its all normal in our body so one could argue that theres no
reason to ban it

Summary of research on the potential benefits of Cr supplementation:

- Cr supp is common practice among athletes => its believed to enhance performance of short, powerful activities, esp when
repeated
- research indicates that it can increase musc PCr, but this is highly variable results among indivs
- the required dose is 3G/day, a larger dose is not necessary
- ingestion of carbs w/ Cr may incr Cr uptake
- Cr supp does not incr max strength, the rt of force prod, or aerobic exercise performance in young adults => but some benefits are
seen in older populations
- most studies have been conducted w male young adults => not much is know about the effect of age and sex but
- it has been found to improve bone density in post-menopausal women (the mechanism of this is unknown)
- evidence exists that medical use of Cr supplementation is beneficial in some patients
- ex. Neuromuscular disease and musc dystrophy
- these potential health benefits are only seen when Cr is combined w resistance or interval training
- the widespread benefits of creatine is mostly overestimated

What about the other two systems of energy production?

- syst 1 we’ve already talked about
- the free adp serves as a substrate and an activator of the other 2 systems
- its the key molecule that is used to drive syst 2 &3
- all three systems are designed to regenerate atp

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2. How does ADPf activate PFK, and therefore the glycolytic pathway?
- glucose comes into the cell —> gets converted to fructose 6-P
- glucose is a 6c sugar, fructose is a diff shape so on the C-6 thats where the phosphate group is
at
- fructose-6-p is converted by an enz called PFK Phosphofructokinase —-> to Fructose 1,6,diP
- there are many enzys that’ll convert f1,6dip into pyruvic acid — make atp
- pyru acid will either go to the mitochondria or is converted into lactic acid
- key rxn: the PFK
•pretend you’re at York and pretend you live in like Ajax
- you gotta get on the 401
- you can drive at 90km/hr but then theres construction at Yonge st.
- construction reduces the lanes down to 1 lane
- so now you gotta drive 25km/hr at Yonge st
- get past Yonge st and youre at bay view and now you can pick up the speed
again
- what is determining the time it takes you to get to the place you want?
- its not the highway a warden and its not the highway at yd, its how long it takes you to get thru the Yonge st construction
- the construction is the rt limiting step basically
- if you can widen the road at Yonge st then it would be quicker to get home
- this analogy is the same as PFK
- to get to pyruvic acid you have to get through the block at PFK
- the greater that “road block” opens up the faster the prod can be produced
- free ADP interacts w/ PFK and makes the rxn go faster

All enzymatic rxns can be characterized byvMichaelis-Menton Kinetics:

S————————->P
Enzyme
- theyre (m-m) 2 biochemists that described the kinetics of converting a substrate (S) into a product (P) thru the action of an enzy
- the kinetics: Ex. You have 30 enzy molecules
- the more substrate you add to the cell w/ the 30 enzymes , the faster the eny will be able to bind to the substrate and
convert it to a product

- the more you fill up the enzymes w the substrate the more and more product you’ll make, until you get to a plateau in which
all 30 of those enzyme molecules are saturated w/ substrate
- *okay my understanding of it: enzymes increase the rate of production so the more substrate you have the faster the rate of
production of the end products via the enzymes*
- the maximum plateaus eventually
- thats the Vmax of the enzyme
- every colour represents a different enzy —> every enzy has its own Vmax
•How do we characterize these kinetics, which are different for each enzy reaction?
- The Vmax is the max velo of the rxn, and it can change if the # of enzy molecules incr or decr in the cell (as a gene
adaptation to training)
- the Km is a theoretical number which represents the substrate concentr that elicits 50% of the Vmax for that rxn; it is an
indication of strength of the interaction (i.e. the affinity) of the enzy for the substrate
- in the ex. The Km = 13mM
- Km may be higher or lower than the actual physiological concentr of the subst in the cell, and it can change if the enzyme
alters its conformation (as in acute exercise)

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How does ADPf activate PFK?

•1.
- The substrate moves into the active site of the enzyme where it will be converted into the product
- its a loose fit so itll fit then fall out —> the strength of the interaction is not as strong => low affinity condition
- enzymes like PFK also have an allosteric site where a molecule (ADP in this instance) can bind and change the conformation of the
enzyme so that the substrate can fit better (2.)
•2.
- free adp binds to the allosteric site of PFK and changed the shape of the enzyme to incr the affinity of the enzy to substrate
- makes it more reliable
- in the absence of free ADP (pink) - the more substrates you have the
more interactions you have thus the more prod you have til you reach
saturation
- Km = 13mM
- now during exercise theres plenty of ADPf so it changes the
conformation of the enzy - (green)
- Km ≈ 5mM
- so even at low concentration you get very high products til saturation

- the lower the Km the greater the affinity of the interaction

- allosteric activation of PFK results in a greater rt of product formation at any [F6P] => higher rt of glycolysis => more lactate prod
but also more ATP

3 Situations: happens
when YOY 2x the ency

i
1.S 1Enzyme P1 '

- suppose that you have 30 molecules of enzy to begin w/ in the cell

2.S1 enzys P1
mod
'

- now you have 30 mols of allosterically mod enzy in the cell (as a response
to acute exercise

3.S1 more P1enzys

"

- suppose that you now have 60 mols of unmodified enzy as a result of an

adaptation in gene expression (as a response to chronic exercise training)

This is w/ ADA

expression
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 Lecture 5 - Sept 20 2021
Quiz:
1. How does acute exercise modify:
a) PFK kinetics
b) Vmax of PFK
2. How many cycles are there in the β-oxidation of a 14-C fatty acid?
answer = 6

Overview of Aerobic System Metabolism:

Carbohydrate and Fatty Acid (FA) metabolism pathways in the musc

- aerobic syst metabolism is metabolism for metabolism for aerobic exercise (long term exercise) and it is activated at the same
time as all the other systems
- it takes time to ramp up to become a steady state supplier of energy —> 3-5 mins to getup to supplying most of the energy when
you start to exercise
- this is the metabolism that breaks down big substrates (ie, glucose, fatty acid)
Glucose breakdown:
- C6H12O6 = gluc
- its broken down initially by glycolysis and in the process the 6 carbon mol is split into 2 3C molecule
called pyruvate
- then we follow more steps after that and the 3C pyruvate is turned into a 2C carbon mol called acetyl-
CoA
- the enzy that breaks down pyruvate > a-CoA = Pyruvate dehydrogenase
- The other carbon comes out as CO2 (we blow it out)
- the a-CoA combines w/ a 4C molecule called oxaloacetic acid (oxaloacetate) which is a product of
the KC
- so you end up starting w/ a 6-c molecule
- so the 6c molecule goes under mods to become a 4c molecule at the end
- skipped the KC steps
- so aft a couple of steps along the way CO2 is prod twice so you lose 2 c molecules (hence why you
end up w/ 4
- FADH2 is prod at one step — NADH2 is also is prod too
- ONE ATP is made directly w/in ONE CYCLE (REMEMEBR THERES 2 CYCLES for ONE MOL OF
GLUC)
- as nadh2 and fadh2 enter the ETC, theyre oxidized ; in the process o2 is the terminal receptor and its converted to H2O, the o2 is
used to make water so its called O2 consumption —> its being converted to water

Fatty Acid (FA)

- long fatty chains exists in triglycerides

- triglycerides = 3 FA chains attached to a glycerol backbone
- to breakdown fat you have to cut off those FA chains from the glycerol and you have to take the FA and deliver it to musc into the
mitochondria where its broken down
- they can be a variety of lengths and saturation’s
*C18 is pictured above*
- its very hydrophobic thus doesn’t dissolve in water very well
- double bond = monounsaturated - means 1 place where its not full w hydrogens
- polyunsaturated means many bonds unsaturated
• they can be any lengths and theyre usually even numbers
- in the process of breaking down the FA its chopped into 2 carbon fragments
- the product of the β-oxidization cycle is a-CoA because what happens is in one cycle:

- C18 is put thru a series of enzymatic rxns in which 2C are cut off as a-CoA and 1FADH2
and 1NADH2 is produced for every cycle
- now ur left with 16C which will now go thru the next cycle of β-oxidization and then the
same thing as above happens again
- we do that chopping each time; when you get down to C4 theres only one chop left to do,
the enzymes chop it then youre left w 2 identical fragments which are both a-coa
- so if you have a 18C FA and you put it thru the β-ox youd end up with 9 a-CoA molecules
entering the KC
- it took 8 cycles to get there
 The Aerobic System (ETC)
- this is the most complex pathway, and it’s a contribution to energy is measured as VO2
• mitochondria: made of an outer membrane , inner membrane and a matrix
- space b/w the outer membrane and the inter membrane is called the intermembrane space
**Dash = outer memb ; solid line = IM**
- the IM is very selective of what gets in/out
- inside the matrix space
- ATP is broken down in the cytoplasm —> free ADP
- we take the free adp and bring it into the mitochondria
- the overall concept:
- breaking down ATP -> ADP and bring it into the mitochondria thru a special
carrier and convert it in there back to ATP and then we’re gonna shove it back out the
mitochondria -> cytoplasm where it can be used for work funct

F
matrix space

- gluc and FA enter KC & made NADH and FADH by taking a-CoA and putting it into the cycle
- in the IM of the mitoc we have a series of proteins called the Electron Transport Chain [ETC]
- the NADH and FADH are gonna get oxidized and we’re gonna move electrons down the series of proteins and then pump protons
to the intermembrane space where we’re gonna build up a gradient of those protons and those protons are going to represent a
source of potential energy that we’re gonna use by shoveling them back thru the ATPsynthase channel
- the energy of the protein mvmt is gonna be used to put the bond together b/w the ADP that came in and the phosphate thats
already inside the mitochondria ==> making ATP
- ATP made is sent out
- the etc is made of series of complexes — C1, C2, C3, C4, & C5
- C5 = ATPsynthase
- C4 = cytochrome oxidase [COX] since it oxidizes cytochrome c which is the protein thats made before it
- CoQ = a molecule that shuttles enzy b/w complexes
- C1 = NADH dehydrogenase
• so w/ NADH2 , it has 2 H’s
- (H atom = H+ + one electron that circulates; its neutral)
- C1 splits the atom into 2 parts —> it takes the hydrogen and pumps the H+ ion to the IM space and an electron (e-) moves down
the ETC ; since there are 2Hs you get 2 electrons and 2 protons
- so 2 protons are pumped into the IM space and the elections move down to the end of the C4 where those elections will be
combined w/ O(oxygen but not 02 just O) and 2 protons that are ALREADY IN THE MATRIX to remake H2O
- RECAP: 2 e- move, picked up by CoQ, shuttled thru C3 > cyt C
—- IN THE PROCESS of moving electrons c3 - cyt c , 2 protons are pumped from the matrix to the IM space —> where did they
come from? They were already chilling there
- the rxn is coupled , in order to get those protons pumped e-s gotta move —> no mvmt = no pump
- recap contd: when the e-s get to cyt-c they get transferred to C4 and in that mvmt of those 2 e-s , 2 more prots are pumped from
the matrix > IMS
- so in total from NADH there was 3 pairs of protons pumped to the IM (once directly from NADH2 and twice from them just
chilling in the matrix )
- the pumps are forming a buildup - a gradient of Hions and that gradient serves as a source of potential energy
- think of a cliff @ Niagara Falls :
- extremely powerful and lots of potential energy at the top and when the water falls down theres lots of speed and energy
- if you control the amount of kinetic energy (which is what hydroelectric plants do) - you harness the potential energy and
convert it to electrical energy
- this is the same idea with the ATP synth —> the waterfall is the synth while the top of the cliff was the protons creating that
gradient , when 2H come thru ATPsynth, that kinetic energy is turned into bond energy and if theres free ADP thats sitting at the
active site of the molecule itll be converted using that energy into ATP
- phosphate in in abundance in the mitochondria so it’s not a limiting factor —> the lim factor is whether there’s free adp sitting
or not
- where did that free adp come from? The cytoplasm when we broke the ATP > ADP
- it came in thru a specialized carrier called the Adenine-Nucleotide-Trasnlocase (ANT)
- its a 1:1 transaction —> ADP comes in and ATP is shuttled out
— FADH now: does exactly the same thing BUT its oxidized at C2 NOT C1 then the e-s move to CoQ like before to C3
- instead of getting 3 pairs of H’s pumped w/ FADH youre only getting 2 pairs
- the protons can only go thru the channel 2 at a time
- you end up making less ATP from FADH than NADH

- CoQ is a lipophilic molecule that transfers e- (loves lipids)

- CytC is one of several “cytochromes” in the ETC —> cytochromes cont the red pigment Heme and Heme cont ion e Fe which
accepts and donates e in the ETC (Fe cycles b/w Fe3+ & Fe2+)
- thats what is holding the electron til it move from one cytochrome to another
- pretend for a min you dont have any o2 avail:
- you dont have a way to accept the electrons once they come thru —> the electrons build up —> stops the train basically (traffic
back jam)
- since the rxns are coupled ; if the electrons are stuck protons dont move NO PUMP = no gradient anymore
- not making any more ATP = CELL DEATH x_x
- if you take a drug that inhibits a step in the pathway
- one that inhibits COX for example: cyanide
- ur dead
- you can’t pump the electrons now since theyre backed up; protons aren’t pumped up to make the gradient ==> cell death
- if you have a mutation in the ETC : this occurs in 1/5000 people where you might have COX deficiency
- you can live and still make ATP but not as much as normal ; just enough to live
- abt 10% of normal rate
- Limiting factor: free ADP that comes in cause when it binds to the active site that’s when it opens the channel allowing the 2H to
come thru
- no ADP = close

Questions:
1. What’s the funct of C1?
2. What’s the purpose of the proton gradient?
3. What happens w/ Cox deficiency, or cyanide poisoning ?
4. Is 02 the limiting factor for mitochondrial respiration during exercise? Ur never w/o O2 so NEVER a limiting factor unless you
do something special like go to high altitude or do the BP cuff —> blood occlusion when you block blood flow ; during normal it is
never a limiting factor & not a reason why we make lactic acid

End of lecture
Quiz: Lecture 6 - sept 22
1. See bottom of pg 20
2. Use words to explain how NADH2 oxidation happens to produce ATP

* review of lecture 5 content *

- gradient build up is a source of energy

Summary of Energy System Contributions at the Start of exercise

• we have 3 systs at the onset of exercise :

- right away (the first 20 secs) the ATP-PC syst is providing abt 99.9% of the
energy either from the ATP that’s in the musc or from the PC conversion
- energy demand is set by how intense the exercise is
- set by Myosin ATPase activity
- at the same time that you started using atp-pc syst glycolysis was regulated at
a slower rt
- all 3 steps start right away cause its all the same triggering molecule that
initiates all 3 systems (adp f)

- as soon as you start to accumulate free adp you are turning on ATP-PC, trying to turn on glycolysis, and also trying to shuttle adp
into the mitochondria to activate mitochondrial respiration (ETC)
- they dont all turn on maximally at the same time due to how sluggish and complex they are
So lets pretend youre jogging For 5 mins
- initially youre using the ATP-PC syst
- youre also turning on glycolysis which reaches a peak at around 40/50 seconds and is very high til around 2 mins
- at the 3 min mark the aerobic syst is starting to pick up and by the time we get to 5 mins it’s prod most of the energy
- glycolysis and the atp-pc syst aren’t contributing anymore
- depending on how well trained you are you can accelerate the rt of the aerobic syst use

- they do not operate as a switch but rather as a continuum driven by ADPf

* see on next page in lecture manual (pg 22?) for how this operates for different sports *
- the typical anaerobic sports like fast sprints would need a good atp-pc system since you wont really rely on the aerobic syst ; if ur
a marathon runner youre gonna need a good aerobic system to beg good at that type of event
SO IT VARIES BY SPORT

- looking back at the chart: end prod of glycolysis is lactic acid and lactic acid is a metabolite that is a by prod of glycolysis
(turning on PFK)
- its associated with the fatiguing process
- its an indicator of how much glycolysis was used
- given the pattern above, imagine the changes in PCr and lactic acid during repeated bouts of short term exercise of different
intensities and durations:
- 10-20 sec = low (3-5 mM)
- 45-75 sec = highest (25-30mM)
- this is usually when glycolysis is at its highest
- 2-3 mins = high (15-20mM)
note: lactic acid in blood at rest = 1mM **mM= millimolar**
note 2: the high and highest result in acidosis
- the lactic acid is made through metabolism
+ examine how specifically chosen bouts of Interval Exercise Training can influence the metabolic and cardiovascular systems to
produce training effects

next
page
 Contribution of Aerobic/Anaerobic ATP prod during sporting events

Effect of Interval Exercise on metabolism and the CV syst

- these are common ways of training (ie. HIIT)

what happens: starting at pic 2
- the top 4 graphs show PCr and the bottom 2 show muscle and blood lactate —> this is theoretical
10 seconds of exercise and 20 seconds recovery:
- in the first 10 seconds PCr drops down to about 60% , then you get 20 seconds of recovery —> its a 1:2 work:rest ratio
- PCr then comes back up a bit again during recovery
- then you start to exercise again it goes back down to the 60% (roughly) ; rest again it goes back up then repeat
20 seconds of exercise, 40 seconds of recovery:
- w/ 20 seconds of exercise the PCr drops to about 50%, then you get 40 seconds of recovery so it’ll replenish a little bit more
than how it would w/ 20 seconds of recovery ; then you exercise again and it goes back down , then repeat
30 seconds of exercise, 60 seconds of recovery:
- PCr levels drop to about 30% but then the recovery is longer and gets up to about 60% which is way more than the other two
60 seconds of exercise, 120 seconds of recovery:
- the 60 seconds of exercise ends up bottoming out the PCr (as low as 10%) but the the recovery time takes it back up to a really
high amount (like 80%) — almost 90% of it back because thats how fast the recovery is
Now compare to lactate: muscle and blood
10 seconds of exercise 20 seconds of recovery:
- in musc lactate youre gonna get it to go up about 2/3mM
- lactate diffuses from muscle to blood so itll be a little bit less in the blood than in the muscle (its prod in the muscle and
“transported” to the blood so youll lose a bit of concentr in the process)
20 seconds of exercise
- youre going to get about 4-5mM
- can’t call it severe acidosis at all
30 seconds of exercise
- at around 10mM of lactate in the muscle
- acidosis range
60 seconds of exercise
- deffo at an acidosis range here with abt 18mM of lactate

- acidosis tends to inhibit muscle contraction so its associated with fatigue

- 400m sprints are killer, you could feel the muscle lactate when doing those intervals
- so the point: the shorter the intervals you can avoid the massive acidosis and can probably do more intervals

next page
Effect of Interval Exercise on metabolism and the CV syst
contd

Now looking at picture 1: This is an example of swimming intervals - 15 intervals x45 seconds/bout, 30 seconds pause b/w bouts
(aka reps)
- the bars is the swim speeds during the intervals
- as they progressed thru the intervals their swim speed declined
- lactic acid scale is on the left: they slowly built up lactic acid as they went through the intervals ; deffo activated glycolysis
- blood glucose was pretty steady though out the interval ==> at around 5mM (should be maintain at this number always)
looking at heart rt:
- any gym should have a optimal hr chart for age
- when youre training aerobically you want to have your heart rt within a heart rt training range
- w/ HIIT youre training your heart — elevating the hr
- you start your first internal and you increase the hr to about 170bpm then you take the rest and hr drops to about 140bpm, then
the second interval it goes back up to around 170bpm then rest again but its not long so it doesn’t go back down it just goes back
to about 130/140bpm, then goes back up when starting the other interval
- over the 15 intervals, hr is oscillating b/w 140-180bpm which is within a training hr range that’ll train the heart
- as long as you maintain hr in a hr training range thats appropriate for your age you’ll be training your heart (cv syst)

Aerobic and Anaerobic exercise contributions as a function of exercise intensity

- this is different exercise intensities

_
- atp demand is determined by exercise intensity
- when you do mild exercise atp demand isnt much ; moderate exercise: atp demand is
higher ; intense: atp demand is high
*remember anaerobic = atp-pc and glycolysis*
So looking at mild:
- green line = aerobic energy
- the O2 consumption is fairly flat
- purple circle = energy being supplied by anaerobic systs
- called the O2 deficit ; energy is being provided by the 2 anaerobic systs
- under the green line is energy being fulfilled by the aerobic syst
- yellow highlight: when you stop exercising, O2 consumption continues, it doesn’t
immediately stop, energy demand does stop immediately tho, thats what that green line is,
the O2 consumption slowing going down back to rest
- called O2 debt or excess post-exercise O2 consumption (EPOC)
- the muscle is never really without O2 tho so theres technically no ‘debt’
- lactate is the orange dots at top: resting [Hla] is ~1mM —> [Hla]=lactate
- there was a little blip but not much since its just mild exercise
Moderate exercise:
- slightly more intense
- time for getting to steady state is a bit longer
- bigger O2 deficit and bigger EPOC
- Hla goes up more
*he ran out of time so stopped here
 Lecture 7- Sept 24 2021

Quiz:
1. Can repeated interval exercise affect your aerobic system? Why or why not?
2. What do the terms in pink mean on page 24
3. Draw a graph of VO2 and blood lactate as a function of workload in kg/m/min; identify the important “physiological” parts
of the graph

Aerobic and Anaerobic energy contributions as a function of exercise intensity

- purple circle = O2 deficit
- at the intense exercise its at the highest level
- green line = aerobic syst contribution
- yellow circle =EPOC
- lactic acid is made in a small amt in the mild exercise case cause the anaerobic
contribution is very small —> youd expect that hla would rise above 1mM just a bit in which
it does (red dotted line) Since there is some glycolysis going on
- moderate: the demand is bigger therefore the req for O2 consumption is higher, O2
deficit is greater cuz the intensity is higher —> more contribution to the energy demand
initially by glycolysis and atp-PCr
- hla is prod initially cause of the incr in demand of glycolysis but then over the period
of time that Hla is metabolized and comes back down (red dotted line)
- EPOC is bigger than the mild also since the “debt” is bigger
- theres also a fast decline and a slow decline
- intense exercise: this is a situation in which the work load is very high therefore demand is
very high
- high ATP demand (blue) , the aerobic syst is going to try to match that but doesn’t meet it since youre going to pick a
demand that doesn’t match the workload
- aerobic syst tries by incr the O2 consumption (green line) but then it reaches a max and thats the maximum aerobic
capacity ; youre still able to continue exercising since you still have more systems operating
- the anaerobic systems have to kinda help out and make a contribution to the demand since you’ve maxed out your aerobic
“help” —-> called max VO2 (VO2 max)
- blood lactic acid will be prod at a higher rt initially because you need it right away and itll also continue to be produced
over the entire 10 min period and itll increase ; but then when you stop exercising itll come back down as you metabolize it post
exercise
- youre continuing to prod Hla cause youre still using glycolysis to continue to thruout the 10 mins because the aerobic syst
can’t match the exercise energy demand
- EPOC has a fast component and a slow component of decline
- Effect of endurance training on Hla and VO2 kinetics: black doted line
- vo2 max = CV funct (max) * muscle O2 extraction (max) & these improve with training
- max cardiact output * max O2 extraction gives you vo2 max essentially
- it improves with training since your heart improves its function and your ability to extract O2 increases with training
- lets say a person trained for like 2-3 months
- youd have better heart funct and better O2 extraction so what will happen is that your VO2 max will incr and MAY match
the energy demand that it couldn’t meet earlier since you’ve technically shifted the green line up and to the left as well (THE
BLIACK DOTTED LINE)
- O2 deficit will now be red circle (smaller area —> wont rely as much to the anaerobic syst)
- Hla is also going to be prod less now since you’re using the aerobic syst (dotted line on the hla area) —> now able to avoid
acidosis that lactic acid causes
- also now youll be using less PCr since the aerobic syst is improved
*moderate is also referred to as “sub-maximal”*
 - submaximal exercise

- this is also submaxinal exercise and depicts the kinetics

- intense exercise

Relationship b/w VO2, core temp and PCr during exercise and recovery
So 15 mins of exercise:
- O2 consumption rises from resting til it gets to a steady state
- when you stop exercising your hr slowing comes back own
- breathing rt also takes time to go down
— so you still have excess O2 consumption taking place even though yip
do not need it since you’ve stopped exercising—> this is EPOC
- green dot is the fast phase and yellow is the slow phase
- PCr is going down while exercising but then goes to a steady state ; it
comes to a steady state since the other two systems are helping out
- stop exercise: PCr is going back up really fast (90% almost back in 2
mins of recovery)
- it mirrors the EPOC if you take it in
- what is driving the incr in PCr back to resting? REMEMBER THE CR>PCR
syst

- you have to drive the reaction back to the right to make PCr via CPK
- remember that the drop in PCr is what caused a Cr buildup so now you have it and you’re turning it back into PCr
- PCr resynthesis
- it needs ATP so it is getting it from the aerobic system!
- the mitochondria is consuming O2 and making ATP and that O2 consumption is the “fast phase” of the EPOC ; its driving the
rxn drive back to the right
- EPOC has the slow phase now tho and that has to do w/ body temp
- when you exercise for a certain amt of time the body heats up and you sweat and etc so the core temp incr (red dashes)
- cool down takes a while so that is the slow phase
- increase in temp speeds up chemical reactions ; O2 consumption is a series of chemical reactions in our mitochondria so when
you incr temp youre incr the rxns
- so: high temp causes slow phase
- as your core temp drops so does your O2 consumption
 Effect of changing exercise pace on aerobic and anaerobic energy systems

- this is relevant to every exercise; you never really keep the same pace
• lets say you start out at a relatively slow pace
- your aerobic syst is meeting the demand over the first 10 mins
- tou drop PCr a lil bit
•now you incr your pace aft 10 mins and keep it going to like 17mins
- now you’ve incurred a second deficit (green)
- now that means you used PCr a lil bit mor and now also means that you’ve used glycolysis
in contrast in the little bit in the first 10 mins
- eventually you use your aerobic syst to meet the demand again
- everytime you change pace, youre invoking another O2 deficit
•b/w 17-22 mins:
- pushing to higher energy demand, takes longer for aerobic syst to catch up so ur using
more PCr and glycolysis = generating more Hla

• now if you slow down your pace

- youre replenishing PCr now but not all of it ; hla levels continue to drop as you metabolize it

Measuring VO2 max and the lactate threshold during a graded exercise test on a bicycle ergometer

- graded exercise test means its going to be graded from low med
high higher workload ; progressively incr the workload, and you
measure O2 consumption
- in the graph we are measuring O2 consumption (VO2) in L/min
- work loaf starts at 0 - units: kg-g/min
- at 0 workload O2 consumption is about .25L/min (depends on sz)
- when you start to pedal for 5 mins (300kg—m/min) theres a slow incr
in O2 consumption but then levels off
- incr to about 600kg-m.min then you get another incr in Vo2 to meet
the demand of the exercise

- we just want to know the steady state value

- everytime you move to a new pace, you invoke a new energy demand
- each time youre dropping PCr, incr Hla concentration
- now you get to 15 mins work load is abt 1200kg-m/min —> O2 consumption will continue to go up but now youre hitting your max
- vo2 max is the best measure of cardiorespiratory fitness
- when incr the workload at 1500kg-m/min and youre pushing hard to meet the demand, however the O2 consumption does not
change despite efforts to increases
- so it tell u that w/ progressive incr in load you have achieved your VO2 max
- when you incr workload and VO2 does not change then thats when you know you’ve hit VO2 max

- plot it as a function of workload, not as a function of time —> expressed as

“VO2 as a function of workload”
- take the standard steady state values
- when its flat thats when youre at your max vo2 —> called the plateau of VO2 as
a function of workload and that is the main criteria to tell the person
administering the test that you’ve reached VO2 max
- what happens to blood Hla?
- if you take blood Hla at each of the time pts youd see that its pretty low
(yellow)
- w/ incr workload theres a slow incr in blood Hla but then at a certain point
theres an inflection of hla at a very high rt
- that inflection pt is called the Lactate threshold
 Lecture 8 - sept 27 2021

Quiz:
1. Calculate the lactate threshold from graphs on pg 28-29
2. Calc Serena’s VO2max
3. How can you graphically compare the exercise responses of people when they differ widely in their fitness levels?

Pg 28 questions at the bottom

1. Two criterias:
1) the plateau
2) the lactate value is around 8-10mM —> thats how you know the person you are testing has truly reached VO2 max
*theres 2 more criterias tho that we’ll see in the lab

2) the VO2 max for the lactate threshold in this person ?

- blood lactate goes up pretty slowly and then theres a point where it goes up exponentially—> that is the lactate threshold
- the inflection ; it happens b/w 600-900 kg-m/min
- need to find out what percentage VO2 max it happened at
*using the graph that is on the previous page and on pg 28 of course text*
- the value is at 2.6VO2 (L/min) for when the inflection starts to happen (the intersection of 2 slopes) —> the person’s VO2 max is 4
L/min
- so 2.6÷ 4 * 100 = the % of the VO2 max at which LT took place (lactate threshold = LT)
- = 65%
- are they well trained ? Physically active? Or quite sedentary

VO2 Max:
- is our best estimate of Cardiorespiratory Fitness (CRF) —> bigger # = more fit
- is measured directly using the FICK equation
VO2max = CV * max Musc O2 extraction
= (CV = HR * SV) * (a-v)o2
= Q * (a-v)o2
- we dont use this measure often cause its invasive ; it requires you to be invasive with the subject
- HR is easy to measure; SV is not easy —> its how much your heart ejects every beat which is not so easy to measure; in
order to measure the extraction of o2 across a muscle, you need to know what’s going IN and coming OUT from an O2
perspective —> the arterial - venous content —> to do this you need to have a catheter in the artery and in the vein and measure
the o2 content in them
- this is the most accurate way
- is measured indirectly by open circuit spirometry

- theres a way we can use sub max to predict VO2 max

- these graphs show the stuff we went over in the last
lecture with LT and incr in O2 uptake
- shows that the plateau indicates the Vo2 max at about
3.5L/min
- on the different graph it shows the LT
- LT happens at about 2.1L/min
- which = 63% VO2 max
 Cardiorespiratory Fitness & Longevity
what is the benefit of being fit (ie. having a high VO2 max) or becoming fit in terms of overall lifespan?

- epidemiological studies of large populations (>1000 ppl) showing “association”, not “cause and effect”, reveal that:
1) mortality rats are reduced the more fit a person is and
2) mortality can be reduced if you become fit, after being unfit

- scale goes from very unfit to very fit

- at any particular fitness level, the older you are the higher chance of dying
- the fitter you are though, the lower your mortality rt in the age group

- changing your fitness level helps (but it was done on men so dk about women)
- it’s never too late to go from unfit to fit

Examine the change in blood Hla during incremental exercise in:

1. Normal untrained individuals
2. PFK deficient
3. Endurance trained
4. COX deficient people
*graph on right*
- example of 4 different types of people
- looking at the blood Hla concentration at various levels
- measure it and VO2 and them compare people and their different aerobic
capacities

1. Untrained person: green squares

- vo2 max = 3.0L
- Hla at a certain point will rise exponentially = a lil over 50%
- the Hla threshold for an untrained person occurs b/w 50-60% of VO2 max

2.Trained person: pink circles • • • • •

- training improves heart funct and also cap to extract O2 so they would have
a higher VO2 max
- vo2 max = 4.0L
- HlaT = around 70-80% of their VO2 max
Compare: trained v untrained
- HlaT is higher in a trained individual than untrained individual
- it indicates that when you have a better aerobic system like a trained person does you rely less on glycolysis

- the lactate threshold test is “diagnostic” of the capacity of the aerobic system

3. COX deficient people: orange dots

- C4 enzy activity is only like 10% of a healthy individual —> etc still works at resting level but doing aerobic exercise where you
need to accelerate ATP prod from aerobic prod will be very poor
- exercise intolerance
- therefore the VO2 max is abt 1.5L/min
- HlaT is about 25-30% of their VO2, they start to use glycolysis very very quickly

4. PFK deficient: blue circles

- glycolytic so it doesn’t affect your aerobic sys but they cannot really use glucose as a source of energy
- VO2 max is abt 2L
- they are exercise intolerant because they can’t use gluc as a substrate very well
- they are not going to produce much Hla since they can’t really go thru glycolysis
 Why does the lactate threshold change with endurance training?
- go back to michaelis-mention analysis to hep understand

thinner
⑧ Thinner

f) ↳ Thicker

-
↳ thick
* ↳ is this
A vs B
thinner too ?
- the free ADP is the trigger for the onset of 3 pathways
- syst 1: atp + pc = atp thru cpk
Syst 2: adp activating pfk thru glycolysis to make atp
Syst 3: free adp triggering mitochondria respiration and prod atp there
• compare the thickness of the arrow on B — depicts the flow rts
- syst 1 has a slightly thinner arrow
- syst 2 that arrow is significantly thinner
- the one that got thicker is the arrow from pyruvate conversion in syst 3 as its drawn to the
greater #s in mitochondria (pyruvate to lactate also got thinner)

- the mitochondria adapts to training and if you double the mitochondria content in the muscle the
enzymes double (as we discussed previously) (remember lect 4 situation 3)
- 2x mitochondria= 2x many enzymes so 2x Vmax but Km stays the same
- makes it more efficient
- greater chance of ADP interacting w/ mitochondria and incr the rxn
- Vmax has change not the kinetics!
- shifts Lt to a higher point then

Absolute v Relative Workloads

Example 1: resistance workout

- they both go to the gym and theyre asked to do a test

- how much can they lift —> strength test
- max is different
- they do a test lift ; submaximal test
- who’s working the hardest? JG is since he’s working at 50% of his
maximum

- ZC is only working at like 25% of his max relative to his max

 Lecture 9 - September 29 2021
Quiz:
1. Calc Serena’s VO2 max
2. What is apoptosis?
3. P.36 question
4. Summarize why there is a sex difference in VO2 max

Absolute vs Relative Workloads

We did example 1 already - Canada vs US jkjkjk
• first graph measures their VO2 for submaximal
- theyre jogging
- running at 2L / min —> they are running at the same ABSOLUTE
workload hence why the line is better
• now theyre doing the max VO2 test which is the second graph
- so as exercise intensity incr their o2 consumption incr
- Bianca’s plateaus at 3L/min ; Serena plateaus @ 4L/min

Q1. Who was working the hardest during the submaximal workout?
A: bianca was working more: 2/3 = 67.7%
for Serena it would be 2/4 = 50%
Q2: who is the most fit ?
A: Serena would be the obvious choice since her vo2 max is higher
but we also need to take into account the person’s weight (size)
- size of a person makes a difference when talking about O2
consumption per min

- a 3 yr old child would have a lower vo2 max than a 7ft ball player
since the 7ft player is MUCH bigger than the baby
- so from an absolute point of view if you measure the total amt of
L of o2 being consumed you’d argue that the ball player is more fit
than the child
- you need to take into account their size
- so w/ Bianca she’s 110lbs and Serena is 160 lbs so the best way to express this is pound for pound —> the absolute number
doesn’t tell much
- so doing a correction for body sz —> take the VO2 (put into ml) and div by body sz in kg
- ex. W/ Bianca: 3000ml O2 (converted from L) —-> now div 3000 by body sz (kg)
= 3000÷50 = 60o2/kg/min
- so now Serena’s calc: 4000/73 = 54.79O2/kg/min
- by these calculation we can actually see that BIANCA is in fact the most fit

Examples:
- Vo2 (L/min) is proportional to body mass. A big person consumes more L of o2 than a small person
- a 2000kg elephant could consume 50L O2/min does that tell you how fit it is?
- 50000/20000 = 25mL O2/kg/min which is not that fit at all

Examples of how to measure VO2 in athletes

- coaches and trainers in all sports want to know if their athletes are coming to training camp “in shape”
- the VO2max test is a dreaded part of assessing cardio respiratory fitness prior to “training camp” in any sport
Maximal Aerobic Power (VO2 Max) in various patients and in train and untrained subjects
- need to know: elite top end value and bottom end values (poor o2 consumption due
to disease) ; clinical cond that would affect your Vo2 max ; average person’s vo2 max
- these are all male values tho
- top end: cross country skiers - use their arms and legs so lots of o2 being consumed
so they typically have the highest VO2
- around 75-80ml/kg/min is ELITE — or 5.5L/min which is common to many other
athletes
- when you correct for body mass then it gets lower (last pt)
- the avg: 20-25 yrs old -> 35-45 mL/kg/min
- football linemen fall into the “avg” category but they aren’t average theyre trained
in specific tasks but not aerobic athletes
- when you correct for body sz then you get a “true” range
- untrained 50 yr old: 28.4
REMEMBER: VO2 = Q * (a-v)o2
- cardiac probs can effect VO2 and VO2 max ; same w/ muscle probs
- if you have both then Soz
- 50 yr old w/ heart disease: = 20.4
- 50 yr old cardiac transplant patient: = 17.5
- 50 yr old w/ mitochondrial myopathy: 6-10
- these are the ppl w/ the genetic defects
- affects the MUCLE NOT THE Q

Untrained and Endurance Trained people have the same submaximal VO2 values during a standard work test
Where they differ is in:
1) their capacity for O2 consumption
2) their metabolism during submaximal exercise, and
3) the time required to get to steady state VO2
- In a UT 4L/min is the VO2Max
- at 2L they were working at 50% of their max
- at 3L they were working at 75% of their max
Now the person is trained (T) and is doing the same exact test
- in T they incr their VO2 max to 5L/min -> theyre more fit
- now the workload relative is: 1L is now 20% , 2L = 40%
now,its a lower relative intensity
- their submaximal though was the same ; the peak and the
kinetics are the only things that have changed
- VO2 @ SUBMAX DOES NOT CHANGE
- 2) > a trained person uses lipid during submax and less carb
for their energy source

Q: how do you produce the same relative workload in a T subj, compared to an UT subj?
- you need to increase the workload for the trained person so that theyre working at identical intensity

Next page —>

Age, Sex, and Training status affect VO2max

- first graph is max vo2 with a function of age looking at male and female subjects ; the scale is in L/min so its not corrected for
body weight > exaggerates the difference b/w male and female
- age 10-20 there is a incr in vo2 ; peak is at age 20-25
- regardless of gender its coming down after that
- the difference b/w male and female:
- is about 10-20% lower values due to
1) decr muscle mass/unit body weight
2) decr red blood cells (14 vs 16 Hb/100ml of blood)
- regardless of age, if a person decides to become active they can improve their VO2max
- at any point of age
- One of the things that happens w/ age is that max HR goes down
- 220-age gives a rough estimate of your HR
- hr goes down linearly with age so thats a limit
- muscles also lose mitochondria function and content (few of them and less of them)
- we lose muscle mass with age, becoming more frail
- the loss of muscle mass is called sarcopenia and its due to atrophy and apoptosis of motor neurons and muscle fibers
- the pic on the right: shows the two fibers (T1-ST and t2-ft )
- w/ age we get shrinkage of the type 2 fibers ; T1 stay relatively the same on average - atrophy
- we lose fibers thru a cell death process called apoptosis
- the graph on the right shows the decline in the fibers
- muscle mass in the body is lean mass and that contributes to resting metabolic rt and
- less metabolism as you age means less burning so what you eat will be stored as adipose tissue => as you get older you need
to decline caloric intake
 Lecture 10 - Oct 1
Quiz
1. What cellular processes are involved in sarcopenia
2. Calculate your personal training HR

- metabolic rt goes down w/ age

The important parameters for any training program are:

1) intensity of exercise
2) duration of each exercise bout
3) frequency of exercise bouts (per wk)
4) length of the training progress
- graph w/ frq
- suppose you start at a VO2 max of 40 ml/kg
- if the change is 4ml/kg/min
That means you went from 40 to 44ml/kg/min —> a 10% improvement (calculation =
44-40/40 * 100)
- if you exercise one day per wk for like 2 months ; you’re likely to change your VO2Max
by 4ml/kg
- if you go to 3x per week (all @30 mins) —> the change is bigger maybe 6ml/kg
- if you do 5x per week itll be bigger —> maybe 8ml/kg

- with most training parameters theres a point where you get diminishing returns
- studies indicate that when you go from 5x to 7x you wont see much improvement —> you hit plateau in terms of achieving a
greater Vo2 max
Duration graph
- frq is same @ 3x/wk
- duration 15,30,45,60 CONTINUOUS NOT INTERVALS
- 15 = 4ml
- 30 = way better
- 45 = starting to curve
- 60 = plateau > not better than 45

- frequency and duration always matter

- intensity is very important

- to get the best benefits you need to provide a stimulus to your cardiovascular system
and a stim to your muscular syst so that you can prod some adaptation
- an adaptation = an improvement basically
- walking for example is a good calorie burning exercise but the problem with walking
is that there is no intensity —> need both intensity and frequency
- to ge maximum benefits to improve VO2 max you need to get intensity that is higher
- this is when you train between 50-85% of your VO2 max to get into the optimal
training range
- how do you know what that is when you are training?
- you have comething that correlates very well with VO2 max and thats HR
- using the straight percentage of peak heart rate method an exercise heart rt of 60% to
90% of maximum is roughly equivalent to 50% to 85% of VO2max. W/in this optimal
training range, the stimulus placed on the cardiorespiratory system and skeletal muscles
is sufficient to cause adaptive responses
- so if you know your max HR and you can calculate 60 & 90 % of that then youre in an optimal training range

Next page —>

 Two methods for estimating the training HR range to achieve an estimate of training intensity
- consider heart rt range

- this is from when ur ded to your max if you’re 20 years old (rmr 220-
age)
- pretend its a 20 yr subject

•Formula 2: from the graph on the previous page

- training hr range = 60-89% of max hr
so would = 120-180 bpm —> should be here to get some benefits to improve VO2 max
Mudd intense

- very easy to calculate

- if youre a marathoner since you’ve been training for years you get what’s called a training induced lower heart rt at rest and at
any submaximal exercise = called bradycardia - when you have a lower heart rt at rest
- opposite = tachycardia - high heart rt at rest
- pretend the person has gotten a heart transplant
- they typically have a higher resting heart rt
- they let the intrinsic heart rt go => it’ll beat at roughly at 100bpm - cause theres no neural innervation
•Formula 1 can be used to take in your specific resting hr
- gives a narrower range to train in
training hr range = (50-80% of HRR)+RHR
- so in the ex: HRR = 200-60=140 (its the black arrows)
= [.50(140) to 0.80(140)]÷ RHR (resting heart rt)
= 70-112 + RHR
= (70+60) to (112+60)
= 130 to 172 bpm
- narrower range than below but “harder” to calculate
- its more specific for situations in which RHR is different from expected
•Why not calculate your own training heart rt method using the two methods above ?

It is generally assumed that the more “unfit” you are (ie. the lower your VO2max) the more you will benefit
from a training program:
newb
> example of two people who have initial vo2 values of 30 and 59 mls/kg/min
→
←

- if you’ve never exercised then start to exercise youll obvi see some changes than someone thats already
active
- shown in the graph
- numerically this represents: lower = more benefit
Inready fit

However: a) considerable inter-individual variability exists in the response to training, and b) the training
effect is highly “familial”
The HERITAGE family study showed us that the environment and genetics contribute to 50% of the VO2max response to training,
and the rest of the adaptation is due to the training itself
- The training was:
75% VO2max for 5 days a week for 20 weeks
- total subjects tested were 720
= high and low responders
= average response was abt 400mlso2/min ; avg response of 5 families is shown in the graph
- they picked families and tested them all and figured if there was a family impact on vo2
(familial influence)
- the people generally improved about the same so each bar represents a MEAN
- low responders to exercise training achieve only 2-3% improvement of VO2max
- high responders to exercise training can achieve up to a 50% incr in VO2max
- dotted line = average

Next page ->

Dose-response relationship for medication
- we have 3 people - Normal joe is responding to a drug
- he had a couple drinks last night w/ some friends - sensitive Sam and insensitive
Ian
- the next day they all had a headache so they take a drug (Advil or ibu) 2 each
- effect is diminishing the hangover
For norm joe:
- he got 50% relief by taking 2 pills
Sensitive Sam:
- he’s feeling great at 100% relief
Insensitive Ian:
- still feels like shit — <10% relief
Moral of the story: people differ in sensitivity to treatments
- for Ian he would need about 3 pills to get to how joe is feeling & SSam
would only need 1 pill to get to where joe’s at
- shift to the right shows an insensitivity while a shift to the left shows a high
sensitivity

Dose of exercise, response in terms of VO2max

- so compiled research is in this graph

- red line: gains in VO2 max, optimal training intensity and frq and duration:
- exercise b/w 60-80%; 3-4days/wk; 20-30 mins
- exercising at higher intensity more frequently and longer duration does increase the risk of orthopaedic problems, and cardiac
complications in SPECIFIC populations of people
•recommendation: 4x/wk ; 30min/da ; at 50-85% VO2Max
- will get you to the optimal training intensity, frequency and duration