Lecture 2 - E systems

Question 1

• what does ATP stand for?
• it is the ________ ________ of the cell –> explain
• what are the 3 parts of ATP?
• where are the high energy bonds?

Answer 1

• adenosine triphosphate
• energy currency of the cell –> a high energy phosphate compound which is the immediate and most important source of energy for muscular contraction
• adenine + ribose + phosphate
• in between the 3 phosphates

Question 2

• what is adenosine?
• what are the 2 major energy transforming activities in the cell?

Answer 2

• adenine + ribose
  1. extract potential energy from food and conserve it within bonds of ATP
  2. extract and transfer chemical energy in ATP to power biological work

Question 3

what are the formulas of ATP formation vs degradation?
- endergonic vs exergonic reaction?

Answer 3

FORMATION:
- ADP + Pi –> ATP
- endergonic rxn: uses E –> anabolism
DEGRADATION (ATP hydrolysis):
- ATP + H2O –> ADP + Pi + energy (7.3kcal/mol of ATP)
- exergonic rxn: releases E –> catabolism

Question 4

• what are energy systems responsible for?
• what are the 3 energy systems?

Answer 4

• for matching ATP supply to demand at rest and during exercise
  1. ATP-PCr or phosphagen system (anaerobic alactic) –> formation of ATP via degradation of phosphocreatine (PCr)
  2. Glycolysis (anaerobic lactic): formation of ATP via degradation of glucose or glycogen (also FA and aa but less likely)
  3. oxidative phosphorylation (Aerobic metabolism): formation of ATP by the use of oxygen

Question 5

• under normal conditions, body only stores ___-____g of ATP at any time –> enough to power how many seconds of all out activity?
  -how much PCr is stored in cells?
• does the amount of ATP in body change during exercise?

Answer 5

• 50-100g –> enough to power 10sec all out activity
• about 4-6x more PCr than ATP
• not really! pretty constant!

Question 6

what are the 2 ways to overcome storage limitation of ATP?

Answer 6

1. ATP synthesis proceeds uninterrupted to continuously supply energy for all body’s biological work (from CHO and fat)
2. phosphocreatine (PCr) = another high-energy phosphate compound, stored in muscle cells

Question 7

what are the characteristics (3), role (3) and limitations (2) of ATP-PCr system?

Answer 7

CHARACTERISTICS:
- extremely rapid reaction (fastest way to regenerate ATP)
- extremely sensitive to ATP demand
- rxn catalyzed by enzyme, creatine kinase (CK)
ROLES:
- supply ATP at onset of exercise
- supply ATP at extremely high rates for high power output activities
- energy buffer while other ATP supply systems are “turned on”
LIMITATIONS:
- limited substrate, including stored ATP and intracellular PCr, means we run out of energy supply very quickly (5-10sec)
- speed at which system can regenerate ATP (regenerate through glycolysis or ox. phos)

Question 8

what are the 2 steps/sources of energy for the ATP-PCr system?

Answer 8

1. stored ATP –> used by contractile protein and becomes ADP + Pi
2. PCr + ADP <–> ATP + Cr using creatine kinase
   *but after 10sec, no more PCr, need to replenish stores through rest or low-intensity exercise (1’ for 50%, 4’ for 90% and 8’ for close to 100%) replenished)

Question 9

what are 5 strategies to optimize function of ATP-PCr efficiency?

Answer 9

1. creatine monohydrate supplementation
2. high intensity interval training (30” to 2’ effort)
3. rest and recovery
4. strength and power training
5. tapering before competitions

Question 10

• what is the glycolytic system?
• lasts from ___ to ____ of activity
• there are 2 forms of ________ breakdown that occur in a series of _________ rxns collectively termed __________. –> describe 2 forms

Answer 10

• anaerobic energy system that break down glucose to produce ATP (quickly)
• from 10sec to 120sec of activity
• 2 forms of CHO breakdown –> series of fermentation rxns –> glycolysis:
  1. lactate formed from pyruvate remains end product –> anaerobic glycolysis –> rapid but limited ATP production
  2. pyruvate remains end product –> aerobic glycolysis –> slow but substantial ATP production (through krebs cycle and ETC)

Question 11

does the glycolytic process itself involve oxygen? in both cases?

Answer 11

does NOT involve oxygen!
- whether end product is lactate (anaerobic) or pyruvate (aerobic glycolysis)

Question 12

• what are the 2 main phases of glycolysis?
• glycolysis occurs where?
• what is the net equation of glycolysis?

Answer 12

1. energy investment phase: uses ATP to phosphorylate glucose, preparing it for subsequent breakdown
   - steps 1-5: glucose –> 2 x 2-3-phosphoglyceraldehyde
   - loses 2 ATP
2. energy generation phase
   - steps 6-10: 2 x 2-3 PGA –> 2 x pyruvate
   - generates 4 ATP + 2 NADH
   - occurs in watery medium inside cell, outside of mitochondrion
   GLYCOLYSIS:
   glucose + 2 ADP + 2 Pi + 2 NAD+ –> 2 pyruvate + 2 ATP + 2 NADH

Question 13

what are the 5 first steps of glycolysis?

Answer 13

1. glu phosphorylation. uses ATP! –> traps g-6-p in the muscle! (hexokinase)
2. isomerization to F-6-P (glucose-6-phosphate isomerase)
3. phosphorylation again. uses ATP! –> makes F-1,6,BP *key regulatory step in glycolysis (phosphofructokinase1)
4. cleavage into DHAP and 2-3PGA (G3P) (aldolase)
5. convert DHAP to 2-3PGA (G3P) (triose phosphate isomerase)

Question 14

What are the 5 last steps of glycolysis?

Answer 14

6. oxidation. uses 2 NAD+ and 2Pi –> 2 NADH + 2 (1,3-DPG) (glyceraldehyde 3 phosphate dehydrogenase)
7. 1st ATP generation: to form 2 ATP + 2(3-PG) (phosphoglycerate kinase)
8. isomerization, mutation to 2-PG (phosphoglycerate mutase)
9. reduction/dehydration: produces water: PEP, molecule with high-energy phosphate bond (enolase)
10. 2nd ATP generation step: uses 2 ADP –> 2 ATP + 2 pyruvate (pyruvate kinase)

Question 15

what happens when there is a high demand of energy? which substrate accumulates? what does it lead to?

Answer 15

• when high energy demand, NADH accumulates bc NADH production is bigger than NADH oxidation in ETC (mitochondria cannot keep up with oxidative phosphorylation partly cause O2 is limited)
• therefore, pyruvate + NADH –> lactate + NAD+, using lactate dehydrogenase
  *pyruvate is reduced to lactate –> NAD+ produced can then be used to make more NADH at step 6 of glycolysis

Question 16

what are the characteristics (3), role (3) and limitation of anaerobic lactic/glycolysis system?

Answer 16

CHARACTERISTICS:
- occurs in sarcoplasm and very rapid rate of ATP prod
- has energy “investment” phase: glucose = 2 ATP and glycogen = 1 ATP used to add phosphate to glucose and F-6-P
- has energy “generation” phase: net gain of glycolysis is 2 ATP if glu is substrate and 3 ATP if glycogen is substrate (bc skipped 1st step = 1 additional ATP)
ROLES:
- supply ATP at high rates for high power output activities
- supply ATP in absence of adequate ATP via oxidative phosphorylation
- first step in aerobic degradation of CHO: supplies NADH to e- transport chain –> [La-] is not “zero” at rest!
LIMITATIONS:
- acidosis (ie increase [H+] or decrease pH

Question 17

what are the 2 fates of pyruvate/pyruvic acid after glycolysis?

Answer 17

1. converted to lactic acid/lactate through lactate dehydrogenase
   - lactic acid then is converted to La- + H+ = decrease pH of blood and muscle = acidosis = one of the causes of burn in muscle
2. pyruvate is transported into mitochondria –> converted to Acetyl-coA by pyruvate dehydrogenase complex. Acetyl-coA goest to TCA cycle –> further oxidation to produce E in form of ATP, NADH and FADH2 –> NADH goes to electron transport chain

Question 18

what is the lactate threshold?
- explain difference btw trained vs untrained athletes’ blood lactate threshold?

Answer 18

exercise intensity at which lactate begins to accumulate in blood at a faster rate that it can be cleared
- shift from aerobic to anaerobic metabolism –> leads to slowing down of pace
- trained ppl will have a high lactate threshold, and can go through mod-hard intensity without reaching that threshold
VS untrained people reach threshold as soon as they start mod-hard intensity

Question 19

• what is a test that can measure anaerobic power and capacity?
• what is the difference btw anaerobic power and capacity?

Answer 19

Wingate Anaerobic Test –> most often performed on stationary bicycle: requires 30sec of pedaling at max speed against fixed resistance
POWER:
- maximum rate at which energy can be produced by body’s anaerobic energy systems (ATP-PCr) and anaerobic glycolysis. measure of how quickly body can generate E without relying on O2
CAPACITY
- total amount of energy that can be produced by body’s anaerobic energy systems during a sustained, high-intensity activity. represents ability to maintain high power output over a period of time, relying on anaerobic pathways. increase anaerobic capacity = decrease fatigue onset

Question 20

explain the 4 steps of the pyruvate dehydrogenase complexe

Answer 20

1. pyruvate enters mitochondrion through the mitochondrial pyruvate carrier (MPC) = transport protein
2. 3C pyruvate –> decarboxylated to a 2C molecule + CO2
3. 2C is oxidized –> e- transferred to NAD –> NADH + H+. this step also involves attachment of Coenzyme A to form acetyl-CoA
4. formation of acetyl-coA: 2C molecule attached to coA

Question 21

how many ATP produced from pyruvate dehydrogenase complex? (from 1 glucose)

Answer 21

-1 glucose = 2 pyruvates
- 2 pyruvates = 2 NADH
- 1 NADH = 2.5 ATP

• 2 pyruvates = 5 ATP!

Question 22

what is the name of the aerobic (slow) glycolysis pathway?
- known as what?
- for what time frame of activity?
- briefly explain the 3 main steps of oxidative system

Answer 22

• Krebs cycle or TCA cycle
• 2nd stage of CHO breakdown
• > 120s of activity at moderate or low intensity
  1. TCA cycle degrades the acetyl-coA to CO2 and hydrogen atoms within mitochondria
  2. reduced coenzyme carrier molecules transfer hydrogen to electron transport chain (ETC)
  3. ATP forms when hydrogen atoms oxidize during electron transport oxidative phosphorylation

Question 23

Krebs cycle supplies _______ in the form of _______ ________ (2 ex) to be passed through the ______ to produce _________ needed to combine _____ and ______ to reform _____, which provides _______ for muscle contraction

Answer 23

Krebs cycle supplies [electrons] in the form of [reducing agents (NADH + FADH2)] to be passed through the [ETC] to produce [energy] needed to combine [ATP and Pi] to reform [ATP] which provides [energy] for muscle contraction

Question 24

• does oxygen participate in the Krebs cycle?
• what is oxygen’s role?

Answer 24

• does not participate in Krebs BUT is the final H+ acceptor at the end of the ETC

Question 25

- what are the 3 sources of Acetyl-CoA? before it enters TCA cycle? - how many steps in TCA?

Answer 25

1. glycolysis --> pyruvate --> PDH --> acetyl-CoA 2. protein breakdown --> aa --> deamination --> acetyl-CoA 3. lipolysis --> FA --> b-oxidation --> acetyl-coA - 8 steps!

Question 26

- which steps of the TCA produce products? - net equation for 1 cycle?

Answer 26

step 3: produces NADH + CO2 (isocitrate dehydrogenase) step 4: produces NADH + CO2 (a-ketoglutarate dehydrogenase) step 5: produces GTP/ATP (succinyl-coA synthetase) step 6: produces FADH2 (succinate dehydrogenase) step 8: produces NADH (malate dehydrogenase) 1 acetyl-coA + 3 NAD+ + 1 FAD + 1 GDP + 1 Pi --> 2 CO2 + 3 NADH + 1 FADH2 + 1 GTP

Question 27

where does ETC occur? from where to where do NADH and FADH2 go?

Answer 27

NADH and FADH2 are transported from mitochondrial matrix to inner mitochondrial membrane, where they will enter the ETC

Question 28

explain the 4 complexes of the ETC --> 5 steps ish

Answer 28

*complex 1 and 2: reducing agents formed during glycolysis and TCA (NADH for complex 1 and FADH2 for complex 2) transfer their stored E in form of e- to ETC 1. complex 1 pumps protons from mitochondrial matrix into intermembrane space, creating proton gradient. (e- also given to coQ, reducing it to ubiquinol) 2. complex 2 does NOT pump protons, but passes e- directly to coQ, reducing it to ubiquinol 3. coQ carries e- from complex 1 & 2 to 3 which transfers e- to cytochrome c. --> cyt c shuttles e- to complex 4 4. as e- pass through complex 3 and 4, additional protons are pumped into intermembrane space, enhancing proton gradient 5. e- are transferred to molecular oxygen which then forms water (complex 4), completes ETC

Question 29

why is it critical that O2 accepts the electrons?

Answer 29

bc it removes electrons from the ETC, preventing backup of e- --> without O2, e- would accumulate, halting the flow of e- through the ETC

Question 30

what happens if drug blocks complex 1, 2, 3 or 4?

Answer 30

- if complex 1 and 2 are blocked --> ETC will still work bc e- shuttled to coQ - if complex 3 is impaired, ETC cannot work --> complex 3 = limiting enzyme --> too weak [H+] gradient *didn't talk about in class but i guess no complex 4 = no O2 to receive final e- = baf

Question 31

- the proton gradient (also called what?) establishes a difference in both (2) across what? - which side is high/low potential vs acidic/alkaline?

Answer 31

- also called proton motive force --> both concentration (pH) and electrical charge across inner mitochondrial membrane - intermembrane space: more acidic (high [H+]) + high potential - mitochondrial matrix: more alkaline + low potential

Question 32

- what is ATP synthase? - 2 regions? - what does it do?

Answer 32

- large enzyme complex located in the inner mitochondrial membrane 1. F0 region: protons flow through here 2. F1 region: catalytic site for ATP synthesis - as protons flow back into mitochondrial matrix through ATP synthase, the protein complex uses this E to convert ADP and Pi into ATP: ADP + Pi --> ATP *this happens through chemiosmotic phosphorylation

Question 33

what are the energy intermediates + net ATP synthesized from: GLYCOLYSIS PYRUVATE dehydrogenase KREBS CYCLE for 1 glucose molecule

Answer 33

1 NADH = 2.5 ATP 1 FADH2 = 1.5 ATP GLYCOLYSIS - 5 ATP (from 2 NADH) + 2 ATP = 7 ATP PYRUVATE dehydrogenase - 1 glu = 2 pyruvate - 5 ATP (from 2 NADH) KREBS CYCLE - 1 glu = 2 acetyl-coA = 2 cycles - 7.5 ATP (3 NADH) + 1.5 (1 FADH2) + 1 GTP = 10 ATP per cycle - 20 ATP in total

Question 34

describe the 2 muscle fiber types - generates E through what pathway? - contraction speed? - high what? - color?

Answer 34

SLOW TWITCH (type 1 fibers) - generates energy through aerobic pathway - slower contraction speed - high mitochondrial content, high ATP generating capacity via aerobic metabolism (slow and efficient) --> fatigue resistant - high lactate threshold - red in colour bc high myoglobin content and high blood flow FAST TWITCH (type 2 fibers) - rapid contraction speeds - high capacity for anaerobic ATP production via glycolysis (but short term for type 2b) - type 2a: can switch btw aerobic and anaerobic --> pink in color, moderate myoglobin content --> moderate aerobic capacity -type 2b: white or pale: explosive fibers for high force production

Question 35

what is energy system interplay? - do all energy system function in isolation?

Answer 35

- the way different energy systems in body work together to supply necessary ATP for various intensities and durations of physical activity - 3 energy systems do not function in isolation: they interact dynamically depending on the demands of the activity *as time increases, magnitude at which you're using the system changes

Question 36

- what is the primary function + energy source for all 3 systems?

Answer 36

ATP-PCr: - fct = immediate energy - E source = stored ATP and PCr in muscle GLYCOLYTIC SYSTEM: - fct = produces ATP quickly via glucose/glycogen breakdown - E source = glucose/glycogen broken down to pyruvate --> in absence of sufficient oxygen, pyruvate converted to lactate OXIDATIVE SYSTEM: - fct = sustained E for prolonged activities - E source: CHO, fats and to lesser extent prot to produce ATP via Krebs cycle and ETC

Question 37

- describe the interplay as one energy system goes to the other

Answer 37

ATP-PCr: as phosphagen system rapidly depletes its stores, body begins to rely more on glycolysis GLYCOLYTIC: contributes to energy as the phosphagen system depletes. however, lactate or hydrogen ion build up can lead to fatigue, necessitating shift towards aerobic metabolism OXIDATIVE: during prolonged exercise, oxidative system takes over as primary energy source. however, other systems may still contribute during bursts of higher intensity within the activity

Question 38

what are the 3 main hormones regulating metabolism? + explain what happens during exercise

Answer 38

INSULIN - plays critical role in promoting glu uptake by skeletal muscle cells - stimulates translocation of GLUT4 to cell membrane - enhances glycogen synthesis - promotes storage of fat - during exercise, insulin secretion decreases GLUCAGON: - opposite effect of insulin - stimulates glycogenolysis in liver (to increase blood glu) - promotes lipolysis - during exercise, as exercise intensity increases, glucagon secretion increases ADRENALINE/EPINEPHRINE: - stress response hormone - enhances glu uptake in muscles cells during exercise, independent of insulin - potent stimulator of glycogenolysis in both liver and muscle - promotes lipolysis by activating HSL in adipose tissue - during exercise, levels surge (especially if high intensity), providing both immediate and sustained energy

Question 39

explain hormone regulation (adrenaline, glucagon and insulin) of metabolisme for ATP-PCr system

Answer 39

ATP-PCr: - high adrenaline, slight increase; begins to rise SHARPLY to prepare the body for higher E demandes, tough E is mostly derived from PCr - bit high insulin, stable: no significant change as E is supplied by stored ATP and phosphocreatine, not glucose - low glucagon; minimal change; not actively involved in immediate release of glu during this short duration

Question 40

explain hormone regulation (adrenaline, glucagon and insulin) of metabolism for glycolysis

Answer 40

GLYCOLYSIS: - adrenaline: elevated; stimulates glycogen breakdown in both muscles and liver + increase glucose availability for E production --> decreases a bit to mid levels - insulin: decreased; lower insulin levels reduce glu uptake into non-exercising tissues, making more glu available for muscles --> becomes low - glucagon; slight increase: helps maintain blood glu levels by promoting glycogenolysis in liver

Question 41

explain hormone regulation (adrenaline, glucagon and insulin) of metabolism for aerobic metabolism

Answer 41

OXIDATIVE: - adrenaline stays stable at mid levels; elevated: continues to support glycogenolysis and lipolysis, promoting sustained energy production form both glu and FA --> shift to fat oxisation - insulin stays low to prevent excessive glu uptake into non-active tissues and to ensure glu availability for working muscles - glucagon increased; supports continues glu supply through glycogenolysis and gluconeogenesis as glycogen stores are used up

Question 42

what are the metabolic adaptations fo aerobic vs anaerobic training?

Answer 42

AEROBIC: - increased mitochondrial density (# of mitochondria in tissue) - enhanced mitochondrial biogenesis (capacity to produce more mit.) + more capillaries! - enhanced oxidative enzymes (all enzymes in krebs cycle) ANAEROBIC: - increased glycolytic enzymes (enzyme in glycolysis) - increased muscle buffer capacity (buffers lactate --> quicker clearance of lactate + use for E (Cori cycle)) --> allows an individual to perform at higher intensity for a longer period before fatigue sets in, delaying onset of acidosis

Question 43

what is a key factor to determine oxidative capacity?

Answer 43

mitochondrial density