KIN2CC3 Cardiorespiratory Final

bioenergetics

transfer of energy in living tissue via chemical reactions

ATP regulation

• supply & demand basis → determine metabolic pathway

• controlled most by myosin ATPase in exercise, activated by muscle contraction

factors to consider when considering supplements

• side effects

• dosage

• target tissue

• generalization

• life style

• purity

• circulation

byproducts vs end products

byproducts: leftovers from chemical reactions

final product: final byproduct, no energy left

enzyme mechanisms

• work as a catalyst to speed up reactions via lowering activation energy needed

• facilitate by pulling substrates together → use active site to form enzyme-substrate complex

factors affecting enzyme activity

• pH (ideally 7.0)

• temperature ideally ~40^o C

• substrate concentration

• product concentration

• presence of modifiers (limiters/stimulants)

V_max

• max enzyme concentration rate

• can be increased through training

• increase of protein → more enzymes

• can also be increased through drugs

k_m

• half maximal enzyme concentration

• predict affinity of enzyme

modulator mechanisms

inhibitors: inhibitor mimics substrate, binds to the enzyme and blocks substrate

stimulators: open up binding site

modulators relevant to exercise

inihibitors: ATP, hormones (nep/ep), temperature & pH lowering (lactic acid)

stimulators: ADP, bicarb supplements, hormones (ex adrenaline)

anabolism vs catabolism

anabolism: breakdown, energy release (ATP → ADP)

catabolism: synthesis of molecules (ADP → ATP)

• both occur simultaneously, net catabolic (exercise) or net anabolism (rest/recovery)

fuel stores

• liver glycogen (200-400 kcal)

• muscle glycogen (2000-3000 kcal)

• muscle creatine (8-10 kcal)

• muscle triglycerides (2000-3000 kcal)

• adipose (50 000 - 100 000) **potentially infinite

can be affected by diet but only liver can release glycogen into the blood

phosphagen breakdown pros & cons

pros: quick, 1 step, does not use oxygen

cons: limited storage of phosphocreatine, long recovery

non-oxidative metabolism pros & cons

pros: no oxygen, quick

cons: limited storage

oxidative metabolism pros & cons

pros: many choices & storage, lots of ATP available

cons: slow, needs oxygen, needs to occur in mitochondria

phosphagen breakdown location

cytosol

phosphagen breakdown storage form

phosphocreatine in the cell

phosphagen breakdown usage

rest → exercise transition, high altitude, intensive exercise & workload transitions

oxidative metabolism location

mitrochondria

oxidative metabolism storage forms

tg, fa, glycogen, glucose & amino acids

non-oxidative metabolism location

cytosol & cell membrane

non-oxidative metabolism fuel storage

glycogen & glucose

glycolytic cycle steps

glycogen in liver → glucose in the blood → glucose in muscle cell (transported via glut transporter) → G6P (phosphorolized to stay in cell via hexokinase, ATP → ADP) → 2 Pyruvate (2ADP-ATP, phosphofructokinase)

glycogen vs glucose

glycogen: uses phosphorolase to become G1P to G6P, does not use ATP, net 3 ATP

glucose: net 2 ATP

krebs/citric acid cycle

pyruvate [3C] → acetyl coA [2C] (pyruvate hydrogenase) → oxaloacetate [4C] + acetyl coA [2C] → citrate [6C] (via citrate synthase) → oxaloacetate

byproducts of pyruvate oxidation

2NADH

citric cycle byproduct (per 1 pyruvate)

1 ATP, 3 NADH, 1 FADH, CO2

electron transport chain/chemiosmotic theory function

• within inner mitochondrial membrane

• electrons form NADH and FADH passed through membrane to form electron gradient to pump protons out through complexes 1 & 2

• FADH skips complex 1, less chance to pump protons → lower ATP yield

ATP yield of 2H⁺

1 ATP

ATP yield of NADH

1 NADH = 3 ATP

ATP yield of FADH

2 ATP

lipolysis steps

triglycerides in adipose → fatty acid in blood (via hormone-sensitive lipase, regulated by NEP/EP) + glycerol (travels to liver to reform glucose) → fatty acid in muscle cytosol (FA transporter) → fatty acylco-A (via carnitine palmitol transferase/CPT enzyme, 2 ATP-2ADP) → mitrochondria

fat vs CHO?

• CHO more active in exercise

• less exhaustive of O₂

• fat has more storage & ATP yield, but less dependent

• oxidative metabolism used during resting states or steady exercise >20 min

beta oxidation

fatty acyl co-A → 2 carbons removed per cycle via B-HAD enzyme to form acetyl co-A, each 2C removed = 1 FADH & 1NADH

acetyl co-A → krebs

problems with protein metabolism

toxic ammonia group, must be discarded

protein metabolism steps

1. deamination

   1. liver or sk muscle (only for branch chain amino acids) remove NH group → ammonia broken down into glutamine (become urea) and alanine (goes to liver to reform glucose)

2. oxidation of carbon skeleton

   1. formation of oxoacids

   2. become pyruvate or acetyl coA

gluconeogenesis

process of reforming glucose in liver

products: alanine (from prot), glycerol (from fat) & lactate (from CHO)

lactate formation

without sufficient oxygen, pyruvate further oxidized to form lactate & NADH as a buffer → changes pH but allows glycolysis to continue

usable capacity of primary fuels

phosphagen: ~15 sec

glycolytic: <1 min

oxidative (CHO): ~90 mins

oxidative (fat): several days

key regulators of fuel usage

• ATP level/ratio (most prominent during exercise)

• SNS hormones

• metabolies (pH, O_2, etc)

• substrate concentration

• product buildup (i.e lactate → pH change → enzyme function suffers)

energy concentrations during exercise for 5s

85% phosphogen, 10% CHO (non oxidative), 5% oxidative

energy concentration during exercise 30s

30% phosphagen, 50% glycolysis, 20% oxidative

energy concentration during exercise 5 min

<1% phosphagen, 20% glycolytic, 80% oxidative

energy concentration during exercise 3hrs

<1 phosphagen, <1 glycolytic, 99% oxidative

wingate test

• 2 mins of maximal exercise to measure anaerobic exercise response

• not all energy is nonoxidative

• peak power approaches %fatigue (loss of power from peak to end)

• usually peaks around first 10 secs

• can tell about athlete’s strengths & weaknesses

intense exercise effect on muscle ATP, PCR & lactate

• lactate concentration jumps after 1 min

• PC quickly drops around 15 sec

• ATP slope lowers, concentration hardly changes because of speed of resynthesis (large usage & production)

direct measure of ATP & fuel usage?

muscle biopsy

phosphagen: pcr difference (1 pcr → 1 ATP)

glycolysis: lactate change, glycogen change (1 lac → 1.5 ATP)

calorimetry

measure of energy expenditure

direct: 1kcal = raise temp of 1 kg water by 1^o C

indirect: 1 L O₂ = 5 kcal

RER

• VCO₂/VO₂

• used to determine fuel mix

• closer to 1 = all CHO metabolism, smaller number = more fat metabolism

• 0.85 RER = 50/50

• assumes no protein contributions & steady state

• limited by hyperventilation (artificially heightens CO₂

average resting VO₂

0.2 L/min or 350 mL/kg/min (1 MET)

average VO_2max

around 10 MET or 35 mL/kg/min, dependent on sex/lifestyle, lung size, etc

F: 20-40 L/min

M: 30-43 L/min

standard deviation

2/3 fall within standard deviation

interquartile range

middle 50%

ventilatory threshold (VO₂)

• incremental exercise test

• indirect VO2MAX measurement

• coincides with lactate threshold

• noninvasive

gas exchange threshold (VOC2)

• similar to lactate threshold, indirect measure

• incremental, noninvasive

intensity & fuel selection

25% VO2MAX: 70% fat, 30% CHO

50% VO2MAX: 50% fat, 50% CHO

75% VO2MAX: 30% fat, 70% CHO

• more intensive exercise relies more on CHO due to oxygen availability

• biggest change in fuels in muscle glycogen & blood FFA

determining VO2MAX

direct: incremental exercise test to volitional exhaustion

• relies on equpiment & motivation

indirect: HR response to submax exercise

• convienent but largely affected by variability

indirect estimate: based on exercise algorithm, lowest individual accuracy

VO2MAX criteria

1. plateau

2. age predicted HRMAX

3. RER > 1.1

4. voluntary exhaustion

lactate threshold

• threshold at which lactate accumulates before body can clear it

• signifies sustainable/unsustainable exercise

• affected by O2 availability, enzyme activity, muscle fibre type, transporters, SNS activity

duration effect on exercise

• depends on diet

• longer exercise → lower use of glycogen, more use of muscle TG & plasma FFA, RER lowers

• more liver contributions by BG

• lower energy expenditure → more glycogen storage

steps to determine specific energy fuel use

1. take VO2 (overall energy use rate)

2. determine RER (%CHO/fat)

3. biopsy to measure muscle glyc- other fat from liver glyc

4. catheter to measure FFA uptake - all other use muscel TG

hormone categories

peptide: key in exercise, protein derives, fast & soluble

steroid: derived from lipids, insoluble and slow

insulin role in exercise

• released by pancreatic beta cells

• glucose/ffa/aa usage increases

• glycogen & tg synth increases

• lipolysis decrease

glucagon effect in exercise

• released by pancreatic alpha cells

• liver glyconeognesis increase

• gluconeogenesis increase

epinephrine effect on exercise

• released by adrenal medulla

• muscle glycogen use increases

• lipolysis in muscle & adipose increases

noepinephrine effect on exercise

• released by SNS & adrenal medulla

• liplysis in adipose increases & cardiorespiratory function increases

hormones during exercise

• all show increases aside from insulin which decreases

cyclic amp system

1. hormone approaches cell membrane

2. enter via receptor

3. binds to receptor & g protein → adenylate cyclase

4. ATP → cAMP

5. inactive kinase activated via phosphorolation

6. kinase activation causes cellular responses

enzyme effected by norepinephrine

CPT (lipolysis increase)

enzyme effected by glucagon

phosphorolase (glyconeogenesis increases)

primary regulators of metabolism

ADP, epinephrine

glucose uptake

• pool of transporters stored in vessicles

• recruited via contraction (Ca⁺ release) or insulin to increase glucose transport into cell

insulin recognition in muscle

rest → 15 units/L per L of bloodflow

exercise → 10 units per 10L of bloodflow

• bloodflow increases but concentration lowers so more insulin travels to muscles

BG and insulin levels during feeding/exercise

feeding: blood insulin increases, blood glucose increases, sk muscle uptake up and other tissue up

exercise: insulin decreases, no change in BG (lowers over prolonged exercise), sk muscle uptake increases greatly (particularly active muscle) while other tissues lower

maintaining BG during exercise

• glucose of inactive tissues lowers insulin & bloodflow

• mobilize of alternative fuels (NOREP increases, FFA uptake increases)

• stimulate muscle glyc use (EP release, phosphorolase activity)

• glucose release from liver stores (glucagon increases)

metabolic adaptations to training

• mitochondrial content increases (size, efficacy, number) → lower workload on mitochondria

• exercise triggers mitrochondrial biogenesis

• more fuel storage & enhanced aerobic usage

• lactate threshold increases as lactate clearance increases and more pyruvate oxidation

• increase of fat transporters → more lipid usage

sustainable workload

• determined by VO2max → increases under training

• determined by lactate threshold (limited by genetics but still changeable)

reasonable values of VO2MAX before & after training at absolute workload

before training:

• VO2MAX 50 mL/kg/min

• VO2MAX 3.5 L/min

• VO2 25 mL/kg/min

• VO2 1.8 L/min

post training:

• VO2MAX 60 mL/kg/min (~20% increase)

• VO2 30 mL/kg/min

adjustments of cardiorespiratory system during exercise

• CO increased (5L/min at rest, ~20L/min at exercise)

• oxygen uptake increased tenfold, CO increased four fold

• CO redistributed → sk muscle recieves more via vasoconstriction/dilation

• tissues adjust O2 removal

systole

contraction phase

diastole

resting phase

avg time of cardiac cycle at rest/exercise

rest: 0.8 sec (0.3 s diastole, 0.5 s systole)

exercise: 0.4 sec (0.25 s systole, 0.15 diastole)

• ratio still 60:40

avg HR at rest/exercise

rest: 75 bpm

exercise: 150 bpm

end diastolic volume

• volume at the end of diastole (rest)

• at rest ~130 mL untrained

stroke volume

• volume ejected from ventricles per beat

• at rest: ~70 mL

• when low, heart rate rises (limited by HR_max)

exercise effects on stroke volume

• SV and max SV increases

• ejection fraction increases, systolic reserve volume (leftover blood) lowers

• preload increases → more forceful contractions & heart is filled more (frank-starling)

• reserve volume stays the same

frank-starling law

• as EDV increases, pressure increases & strength of contraction increases

• due to elastic recoil of cardiac muscle → more blood = more stretch = stronger contraction

• within physiological limits, contraction from previously stretched muscle is much stronger, pumps greater volume

CO at rest, trained & untrained

HR * SV = CO

• typical HR 75 bpm & SV 60 mL per beat → CO = 4.5 L/min

• after training, HR lowers while SV increases

COmax for trained & untrained healthy 20 yo

untrained: 200 HRmax, SV 100, Qmax ~20-28

trained: 200 HRmax , SV 140, Qmax ~28

predicting maximal exercise via HR

• not a good predictive test individually

• can be used to predict max workload

• fitness indicated by less steep HR increases → shows lower HR at fixed workload → less stress on heart

• indirectly used to predict VO2MAX

regulation of CO

• chronotropic: rate of contraction (HR, beta blockers, neural/hormonal control mechanisms)

• inotropic: affect strength of contraction (SV), neural, hormonal or mechanical control (frank-starling)

neural control of CO: PNS

• innervate SA node

• primarily via vagus nerve which slows SA node firing (typially 100 times/min) via acetylcholine release

neural control of CO: SNS

• more complex than PNS, innervates SA node, ventricles & arterioles/veins

• norepinephrine release via cardiac accelerator nerves → speed up SA node firing

hemodynamics during exercise

• flow, pressure & resistance control bloodflow

• flow inversely proportional to resistance (which is most affected by radius)

• veins & arterioles vasoconstrict towards to redirect bloodflow

• vasodilate near sk muscle, dilation slows bloodflow → more time for gas exchange

• more capillaries open to allows greater surface area for gas exchange

bloodflow to tissues during rest

resting CO: 5L/min

muscle: 1 L/min (20%)

splanchic: 1.25 L/min (40%)

heart: 0.2 L/min (4%)

bloodflow to tissues during maximal exercise

COmax: 25 L/min

sk muscle: 20 L (80%)

splanchnic: 1 L/min (5%)

heart: 1L/min (4%)

ejection fraction

fraction of blood ejected by ventricles, ~55% (i.e 130 SV → 70 ej. fraction)

• percent form of SV

preload

stretch on ventricles from filling → determines strength of contraction

muscle pump

• rhythmic contraction of sk muscle in aerobic exercise

• pushes on veins, promotes venous return → greater EDV

• when relaxing, sucks blood back into muscle & pumps to heart when exercising

calculating HRmax

1. 220- age

2. THR = HRrest +0.6(HRmax - HRrest)