Exercise and metabolism

muscle consists of 1000s of muscle fibers

muscle fiber = muscle cell

inside each muscle-specific protein: myofibrils composed of actin & myosin

skeletal muscle linked to bones to allow movement

100s of different skeletal muscles (& smooth muscle)

average length of skeletal muscle cell 3 cm (sartorius muscle up to 30 cm (thigh), stapedius muscle 1 mm (inner-ear)

diameter varies from 10-100 um

myofibrils difference from other cells allowing contraction

filaments of actin & myosin overlap —> structured in functional units repeating 1000s of times

disposed in the length of muscle cells, contraction due to increased overlapping of actin & myosin

myosin heads link to actin & pull actin towards the center —>macroscopic reduction of muscle

one functional unit goes from 3 um to 1.5 um in the contracted state

skeletal muscle highly structured & composed of repeated functional units

ATP binds the myosin head & chemical energy from hydrolysis is transferred to the myosin head —> changes conformation

increase in cytoplasmic Ca2+ binds troponin on actin filaments unmasking the binding site of the myosin head

muscle contraction in presence of Ca2+ & ATP —> 90-100x / min contraction & relaxation while running

—>thight control needed

tropomyosin has a structural role in the correct distribution of troponin

signal for contraction comes from the brain & goes down the spinal cord via efferent neurons

heart sends nutrients to produce ATP & lungs provide oxygen for aerobic metabolism but contraction only after signaling from the brain

1. action potential generated & propagates along sarcolemma down the T-tubules

2. Action potential triggers Ca2+ release from ER

3. Ca2+ binds troponin —>conformational changes —>removes blocking action of tropomyosin —>actin active sites exposed

4. contraction, myosin cross-bridges alternately attach to actin & detach, pulling the actin filaments toward the center of the sarcomere, release of energy by ATP hydrolysis powers the cycling process

5. removal of Ca2+ by active transport into the SR after the action potential ends

6. Tropomyosin blockage restored blocking of actin active sites, contraction ends & muscle fiber relaxes

oxygen & metabolic substrates must reach skeletal muscle to ensure ATP availability

1 muscle cell connected to half a dozen capillaries depending on training & genetics

capillary has the size of a red blood cell —>pass 1 after the other & carries oxygen (hemoglobin), no nucleus

few glycolytic molecules & no mitochondria —>efficient O2 transfer without using it itself

hemoglobin has 4 binding sites for O2 that are occupied depending on the partial pressure of O2 around it

high partial O2 pressure: in the lungs —> hemoglobin fully saturated

travels some minutes to go from the lungs over the heart and via the vascular system into capillaries of skeletal muscles

low partial O2 pressure: in capilalries of skeletal muscles (hemoglobin releases O2)

myoglobin: has 1 subunit binding O2 & can bind O2 at partial pressure present in skeletal muscles (high affinity)—> released O2 in intravascular space pulled by myoglobin

—> Difference in affinity important

oxygen needed in every cell for nutrient production ->transported in the bloodstream

in the lungs alveoli are filled with air (the last compartment with direct contact with the atmosphere)

blood enters the lung with a low level of oxygen & leaves with a high level

the time needed to go through the capillary system of the lung allows hemoglobin to be fully saturated with O2

capillary blood collected —> goes through the left ventricle of the heart & distributed —> part goes to capillaries of skeletal muscle & release O2 from hemoglobin —> collected in vein, back in right ventricle of heart & sent to lung

red & white muscle fibers but also a continuum in between

red color by myoglobin

ratio of red & white fibers determined by genetics & can be pushed by training

type 1: red fibers with a high level of myoglobin, high aerobic metabolism (oxidative metabolism, many mitochondria), high resistance to fatigue & slow contracting, lower contraction power but modest at a long time, thin

type 2B: low amount of oxygen—>glycolytic metabolism, fast contraction but rapidly exhausted by exercise, more voluminous (sprinter bigger than marathon runner)

type 2A: pink fibers

differences in glucose, lactate & fatty acid metabolism between fast & slow muscle fibers

fast (white fibers): glycolysis, full of glycolytic enzymes & many glucose transporters

slow (red fibers): relies on FA metabolism & much more mitochondria present —> different enzymatic & mitochondrial status

measured by biopsies

possibility to switch from type IIb to IIa —>push preexisting fibers (white —> pink) if trained aerobically

white fibers acquire more mitochondria, capillaries & myoglobin due to training

but no full conversion white —> red fiber, with training only partial switch possible

the main determinant for aerobic performance is genetics, training minor component

24 h energy need of a resting organism

energy for the heart, brain, respiration, digestion, preservation of constant body temperature

parameters influencing: weight, size & age (with age decreased energy need)

2000-2500 kcal needed for daily life, on top training session

consumption of 3.5 mL O2/min/kg at resting state —>basic oxygen consumption level

less than 1 MET during sleeping

18 MET if running > 17,5 km/h —> 18 fold increase in energy expenditure

exergaming: exercise + gaming around 4 MET (similar to normal biking)

400-500g stored & available for ATP production (glycolysis & aerobic processes)

muscular glycogen: 325 g (15g /kg)

liver glycogen: 90-100g (very important —> gluconeogenesis)

blood glucose: 15-20g to maintain glycemia

4 kcal/g of glycogen —> 1600kcal/individual as carbohydrates available

1kcal/kg/km —>600 kcal/h —>3h of running

glucose uptake in liver & muscle —>glycogen synthesis & storage until needed

breakdown of glycogen into G6P used in glycolysis to produce ATP —> in muscle and liver

in liver: glucose-6-phosphatase —> glucose can passively diffuse outside into blood circulation -> can be taken up by cells needing it

triglycerides in adipose tissue - lipid vacuoles between muscle fibers

10 kg for a 79 kg male —> huge in comparison to sugars (400g)

90000kcal (limitless) —> 100g of lipids allow 800 kcal

3 phases in exercise: intensity as a function of time —> 3 metabolic pathways

metabolic pathway: way by which ATP is produced

1. high speed (15-20s) —> non lactic, anaerobic

2. quick decrease —> lactic, anaerobic

3. decrease at a lower rate —> aerobic (most efficient extraction of ATP, respiration & heart function needs to be adapted)

no oxygen —> no waste

not a real pathway

need immediately ATP —> use ATP present in the cytoplasm & P-creatine for ATP production

85g ATP present: no storage of only usable form of energy due to instability —>need ATP regeneration at high speed

provides muscle 2-3 sec with energy & CP for 10 sec

—>allows the switch to glycolysis

glycolysis

ATP due to glucose metabolism in the cytoplasm: glucose —>pyruvate

nothing in the mitochondria: heart rate not yet increased

only cytoplasmic glycolysis

lactate produced: released from muscle & captured by the liver —> transition to glucose

sources of ATP after phosphagen exhaustion: glucose & glycogen

releases 5% of the total amount of energy available form glucose oxidation

cross of metabolic pathways at 3-4 min

if not too fast run exclusively aerobic after 10-15 min

switch anaerobic to aerobic

after increased heart rate & breathing frequency —> more oxygen-rich blood pumped & provided to skeletal muscles

pyruvate enters mitochondria —> Acetyl-CoA

used in the Krebs cycle, then the respiratory chain to produce ATP

1 glucose = 34 /36 ATP —> more efficient than anaerobic glycolysis

amount of blood delivered by heart: pumps under stress 5 times more blood/min

5L/min at rest & at Absolute perfusion 25 L /min

at rest, 15-20% of blood is delivered to muscle cells, under stress 80-85%

large range between resting & maximal exercise —> more oxygen & nutrients delivered

maximal volume of oxygen consumed per unit of time during maximal aerobic exercise

determines the volume of consumed oxygen

depends on:

• lung capacity (surface of interaction)

• blood oxygenation by the lungs

• cardiac output (amount of blood the heart can push during contraction)

• total blood volume

• total body hemoglobin (used in doping)

• muscle blood flow (the more capillaries, the more RBC can pass)

• muscle oxygen extraction

highest ever measured 99,5 (but probably doping)

VO2max values 50-100% greater than those seen in normally active healthy young subjects (45-50mL/min/kg) are seen in champion endurance athletes

training: stroke & blood volume, capillary & mitochondrial density

the upper limit of aerobic power officially measured without doping: 90,6 mL/min/kg

in female slightly lower (higher fat mass)—>testosterone increases muscle mass & reduces fat mass

difference between species ( in antelopes > 300 mL/min/kg)

with VO2max increase of MET (up to 25-fold)

without disease life-expectancy dependent on VO2max —>classified according to MET

prognostic of normal people & high-level athletes that trained > 50 years of consistent exercise training without no more than 6 months of no training

athletes with a history of vigorous aerobic exercise (4-6 days/week)

compare VO2max with classical octogenarians

with aging VO2max slowly decreases until not able to sustain life

in athletes, VO2max doubled

VO2max is not the only important parameter —> with identical VO2max different endurance / performance

lactate threshold: at comfortable pase 40-50% of personal VO2max, if faster (increased intensity) 60-70% VO2max & increase in blood lactate—>could go higher in oxygen consumption but additional ATP via glycolysis provided

pure aerobic: mainly FA burnt —> no glycolysis

aerobic + anaerobic: additionally glycolysis —> not all pyruvate can be used in Krebs cycle —> reduced to lactate

lactate correlated to the synthesis of protons

acidification —>muscle fatigue

the more lactate produced the lower the pH —> not good for muscle contraction

erythropoietin

EPO receptor expressed during differentiation of blood cells —> exogenous EPO pushes undifferentiated

cells into differentiated RBC —> increases hematocrit & oxygen carrying capacity

EPO = erythropoiesis stimulation —> endogenous molecule (undetectable in the beginning)

designs to differentiate endogenous & exogenous EPO —> circle of new doping strategies until detectable

between 1989-2001 abnormal increases in Hb in world-class cross-country competitors

Virenque: 500 EPO doses over 5 years

take low doses all year long —> no changes in biological passport

the maximum power that can be delivered increased by 10-15% at low doses for 3 months

huge in respect to differences at high-level sport