Wk 2 - bioenergetics, exercise metabolism and hormonal responses to exercise Flashcards

1
Q

What are bioenergetics?

A

-Bioenergetics -> Flow and exchange of energy within a living system. Conversion of foodstuffs (fats, proteins, carbohydrates) into usable energy for cell work. ‘Chemical -> mechanical’.

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2
Q

What is metabolism?

A

-Metabolism -> Sum of all chemical reactions that occur in the body.
* Anabolic reactions – synthesis of molecules e.g. glucose being stores as glycogen
* Catabolic reactions – breakdown of molecules e.g. glycogen being broken down into glucose

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3
Q

What are cellular chemical reactions?

A

-Cellular chemical reactions -> Energy cannot be created or destroyed only transformed from one form to another (1st law of thermodynamics). Endergonic = requires energy to be added to the reactants. Exergonic = releases energy.
-Cellular chemical reactions: coupled reactions -> Liberation of energy in an exergonic reaction drives an endergonic reaction.

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4
Q

What are oxidation-reduction reactions?

A

-Oxidation-reduction reactions -> Are always coupled reactions. Oxidation = removing an electron. Reduction = addition of an electron. Nicotinamide adenine dinucleotide (NAD) and Flavin adenine dinucleotide (FAD) play an important role in the transfer of electrons, acting as ‘carrier molecules’ during bioenergetic reactions.

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5
Q

Describe enzymes: catalysts for reactions:

A

-Enzymes: catalysts for reactions -> Enzymes are proteins that lower the energy of activation and accelerate chemical reactions. Increased rate of product formation. Enzymes are not consumed or changed by the reaction they are involved in.

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6
Q

How do enzymes lower the energy of activation?

A
  • Kinase – add a phosphate group
  • Dehydrogenases – remove hydrogen atoms
  • Oxidases – catalyse oxidation-reduction reactions involving oxygen
  • Isomerases – rearrangement of the structure of molecules
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7
Q

How does the cellular environment influence enzyme activity?

A

-> Temperature and pH level. pH level – Heavy exercise increases lactate threshold. Increased H+ results in a lowered pH. Lowered pH ATP production and muscular fatigue.

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8
Q

Describe ATP

A

-Adenosine triphosphate (ATP) -> High energy phosphate molecule. Synthesis: ADP + Pi = ATP. Breakdown: ATP -> (ATPase) -> ADP + Pi + Energy. ‘Universal energy donor’. Only small amounts of ATP in intramuscular stores (enough <2s of all-out exercise).

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9
Q

Describe bioenergetics: metabolic pathways activated to form ATP:

A
  1. Anaerobic pathways (substrate-level phosphorylation) – Do not involve oxygen and there is PC breakdown and glycolysis (degradation of glucose)
  2. Aerobic pathways – Required oxygen, oxidative phosphorylation, dependent on respiratory and cardiovascular systems to deliver adequate O2.
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10
Q

Describe anaerobic ATP production: ATP-PC system and glycolysis

A
  • ATP-PC system -> Most rapid (milliseconds) and simplest (one-enzyme reaction) method of producing ATP by phosphocreatine breakdown. Although PC can be reformed with recovery, limited capacity to provide prolonged energy e.g. depleted after 10-15secs all out activity.
  • Glycolysis -> Increase in the by-products of ATP breakdown activates energy influx through reactions of the glycolytic pathway. Anaerobic glycolytic capacity is threefold higher (~30-90s) than the ATP-PC system. Besides ATP, produces: 2 NADH, and 2 pyruvate or 2 lactate.
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11
Q

What is the net gain of glycolysis dependent on the starting point?

A

-> Glycolysis occurs in 2 phases. Net gain of glucose is the substrate 2 ATP. Net gain of glycogen is the substrate 3 ATP.

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12
Q

Describe electron carrier molecules and how it is achieved:

A

-Electron carrier molecules -> For chemical reactions in glycolysis to continue, adequate amounts of NAD+ must be available to accept H+. Therefore NAD+ needs to be rapidly reformed from NADH. This is achieved as follows:
1. If sufficient O2 is available, H+ can be ‘shuttled’ into the mitochondria for ATP generation (aerobic)
2. In the absence of O2, pyruvate can accept the hydrogens to form lactate (anaerobic) (catalysed via lactate dehydrogenase)
+Lacate formation allows the recycling of NAD+ so that glycolysis can continue without O2.

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13
Q

Describe the Krebs cycle and endurance exercise below VO2 max:

A

Endurance exercise below VO2 mx allows time to mobilize substrates from energy stores. In this instance, aerobic ATP generation dominates and results from cooperation between (and the ETC):
* Citric acid cycle -> (Krebs cycle) Completes oxidation (electron removal) of acetyl CoA (formed from fuels fats, CHO, proteins) to provide electrons for the electron transport chain.
1. Glycolysis generates 2 molecules of pyruvate
2. Pyruvic acid (3-C) enters the mitochondria and is converted to acetyl-CoA (2-C), losing a carbon (generating CO2)
3. Acetyl-CoA combines with oxaloacetate (4-C) to form citrate (6-C)
4. Series of reactions to generate oxaloacetate (generating 2 CO2 molecules)
5. Each turn of the cycle, 1 ATP molecule is synthesized from guanosine triphosphate (GTP: high-energy compound) with the release of high-energy electrons (3 NADH and 1 FADH2)

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14
Q

Describe the electron transport chain:

A
  1. Electrons removed from NADH and FADH are passed along a series of carriers (cytochromes) coupled with the pumping of H+ into the intermembrane space
  2. Increased concentration of H+ ions in the intermembrane space
  3. Results in electrochemical gradient
  4. ATP produced as H+ ions diffuse back across the membrane
    +At the end of the ETC, O2 accepts the electrons that are passed along and combines with hydrogen to form H20 (chemiosmotic hypothesis). Without O2 available to accept these electrons, oxidative phosphorylation is not possible.
    + Interactions between metabolic fuels -> Beta oxidation: process of oxidizing fatty acids to Acetyl-CoA
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15
Q

What is the aerobic ATP tally per glucose molecule? + draw the glucose molecule

A

-Efficiency of respiration (energy contained in ATP produced/ total potential energy in a glucose molecule)
-In addition to substrate-level phosphorylation (4 ATP), 10 NADH and 2 FADH are shuttled into the mitochondria: total = 32 ATP molecules -> total = 38 ATP molecules. Total ATP is variable as NADH is used as a reducing agent in other processes and the proton gradient is used in transporting other substances through the inner membrane into the matrix.

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16
Q

What is feedback inhibition and what are the rate limiting enzymes?

A

-Biochemical pathways are regulated by very precise control systems (feedback inhibition)
-Rate limiting enzymes:
1. Are found early in a metabolic pathway
2. Activity is regulated by modulators

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17
Q

What are the metabolic responses to exercise: influence of duration and intensity

A
  • Short-term, high intensity exercise (<5 secs) – ATP produced via ATP-PC
  • Intense exercise > 5 secs – shift to ATP production via glycolysis
  • Events lasting > 45 secs – ATP production through ATP-PC, glycolysis and aerobic systems. 50% anaerobic/ 50% aerobic at 2 mins.
  • Prolonged exercise (> 10 mins) – ATP production primarily from aerobic metabolism.
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18
Q

Summarise cellular respiration in 3 points

A

-Muscle cells store limited amounts of ATP, given exercise requires a constant supply of ATP to provide energy needed for contraction, metabolic pathways must exist in the cell that are capable of rapidly producing ATP
-Short bouts of exercise, the contribution of aerobically produced ATP is small because of the time required to complete the many reactions involved in the citric acid cycle and the ETC
-The shorter the duration of all-out activity, the greater the contribution of anaerobic energy production; conversely, the longer the duration, the greater the contribution of aerobic energy production

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19
Q

Describe 4 processes how blood glucose is maintained during exercise:

A

-Blood glucose homeostasis during exercise -> Plasma glucose when fasting or during exercise maintained through 4 processes:
* Mobilization of glucose from liver glycogen stores
* Mobilization of FFA from adipose tissue – spares blood glucose
* Gluconeogenesis from amino acids, lactic acid, and glycerol
* Blocking the entry of glucose into cells – forces use of FFA as a fuel
+Controlled by hormones -> Permissive or slow-acting (thyroxine, cortisol and growth hormone) and fast-acting (epinephrine, norepinephrine, insulin and glucagon)

20
Q

What are permissive and slow-acting hormones?

A

-> Act in a permissive manner to allow other hormones to exert their full effect

21
Q

Describe thyroid hormones:

A

-> Influences the number of receptors on the surface of a cell for other hormones to interact with. The affinity of the receptor for the hormone.
* Triiodothyronine (T3) enhances effect of epinephrine to mobilize free fatty acids from adipose tissues (little effect without T3)
* No real change in thyroid hormones during exercise
* Hypothyroid state interferes with the ability of other hormones to mobilize fuel for exercise (linked to overall metabolic rate)

22
Q

Describe growth hormone:

A
  1. Growth hormone -> Essential for growth of all tissues – increases amino acid uptake and protein synthesis. Spares plasma glucose – Reduces the use of plasma glucose, increases gluconeogenesis and mobilizes fatty acids from adipose tissue.
    * Growth hormone and performance -> GH increases protein synthesis in muscle and long bone growth. High dose: more adverse effects from benefits. No evidence from GH promotes strength gains. Difficult to detect suage by athletes. Questionable benefits as anti-ageing therapy.
    * Changes in GH during exercise -> Net effect of GH is to preserve plasma glucose concentrations – Increases gluconeogenesis in liver and blocks glucose entry to adipose cell to favour fat mobilisation. Increase in plasma GH with increases intensity.
23
Q

Describe cortisol:

A
  1. Cortisol -> Steroid hormone derived from cholesterol and secreted from the adrenal cortex.
    * Stimulated by -> Stress, via Adrenocorticotropic hormone (ACTH) and exercise
    * Contributes to the maintenance of plasma glucose by a variety of mechanisms
    * Considerations -> 1. Diurnal variation: Concentrations peak in the am and drop throughout the day. 2. Events other than exercise e.g. emotional arousal
    * Increases proportional to an increase in exercise intensity -> The direct effect of cortisol is mediated through the slow process of DNA transcription and translation to protein synthesis. Therefore, changes in cortisol may be related to repair of exercise-induced tissue damage rather than the mobilization of fuel per se.
24
Q

Describe catecholamines:

A
  1. Catecholamines -> Secreted from the adrenal medulla:
    - Epinephrine (E ) (80%) and norepinephrine (NE) – Fast-acting hormones, part of fight or flight responses. Bind to adrenergic responses (alpha and beta). Effects depend on hormone used and receptor type).
    * Fast-acting hormones -> Catecholamines.
    * Return Plasma E and NE increase during exercise -> Related to increased HR and BP during exercise e.g. sympathetic activation
    * Endurance training causes a rapid decrease in catecholamine responses to a fixed intensity exercise bout
    * Catecholamine responses to supramaximal exercise -> Trained individuals have a greater capacity (~35% higher) to increase catecholamines compared to untrained individuals. Regular stimulation of the SNS increases capacity to respond to extreme challenges e.g. supramaximal exercise.
    * Glycogen depletion -> Glycogenolysis is related to exercise intensity. High-intensity exercise results in greater and more rapid glycogen depletion.
    * Role of plasma epinephrine -> Plasma epinephrine is a powerful simulator of glycogenolysis. High-intensity exercise results in greater increases in plasma epinephrine.
25
Describe insulin and glucagon:
* Pancreas -> Both exocrine (secreted via ducts) and endocrine (directly into the blood) functions. Secretes counter-regulatory hormones from the islets of Langerhans: - Insulin (from beta cells) -> promotes the storage of glucose, amino acids and fats - Glucagon (from alpha cells) -> promotes the mobilization of fatty acids and glucose. Stimulates gluconeogenesis in the liver. * The ratio of glucagon to insulin provides control over the mobilization of glucose and FFA. Insulin – drives uptake and storage of substrates to lower their levels in plasma. * Changes in plasma insulin during exercise -> During moderate-intensity exercise, insulin concentrations can drop by ~50%. – Favouring the mobilization of glucose from the liver and FFA from adipose tissue. * Changes in plasma glucagon during exercise -> Following an endurance training programme, the glucagon response is diminished to the point that there is little to no increase during exercise. * Effect of catecholamines on insulin and glucagon secretion -> When plasma glucose is relatively constant (trained individual), the SNS can modify hormone secretion. (right)
26
Summary of the hormonal responses to exercise:
-To provide adequate fuel for exercise while maintaining plasma glucose concentration for central (brain) functions is a complex task requiring many hormones -These hormones (except insulin) mobilise fat and CHO and preserve blood glucose
27
What is hormone-substrate interaction?
-> These hormones (epinephrine, norepinephrine, growth hormone, cortisol, glucagon) that are elevated with exercise favour the mobilization of FFA. However, in spite of this persisting hormonal stimulation, FFA oxidation decreases during heavy exercise. May be due to: - High levels of lactic acid - Elevated H+ concentration inhibits HSL - Inadequate blood flow to adipose tissue - Insufficient albumin to transport FFA in plasma Therefore, decreased FFA and increased glucose use.
28
What is the impact of endurance training (with hormone-substrate interaction)?
-> Decreases the lactate concentration at any fixed work rate, which reduces this inhibition to FFA mobilization from adipose tissue. When this is combined with the training-induced increase in mitochondria, the trained person can use more fat as a fuel, spare the limited CHO stores and improve performance.
29
What are the energy requirements at rest?
-Almost 100% of ATP are produced by aerobic metabolism -Blood lactate levels are low (<1.0mmol/L) -Resting O2 consumption -> 0.25 l/min (3.5ml/kg/min). This is considered the baseline for activity units
30
What are the rest-to-exercise transitions?
-ATP production increases immediately. (∆ in metabolic rate can be 25-fold) -Oxygen uptake rapidly increases -> Reaches steady-state with 1-4 minutes. At steady-state primary ATP production processes are aerobic. -Initial ATP production must be through the anaerobic pathways (ATP-PC system -> glycolysis) -This creates an oxygen deficit -> Discrepancy between initial demand/ ATP production and oxygen consumption
31
Why do endurance trained individuals have a lower O2 deficit than untrained?
-Better developed aerobic bioenergetic capacity: * Greater regional blood flow to active muscles (e.g. more capillaries) * Increased cellular adaptation and efficiency * Increased mitochondrial volume in muscle fibres results in less lactate production at beginning of exercise
32
Describe recovery from exercise (oxygen):
-Oxygen uptake remains elevated above rest during recovery from exercise -Oxygen debt -> Term coined by A.V. Hill. Hill believed that the elevated O2 consumption post exercise was repayment for O2 deficit at onset of exercise. Oxygen deficit concept provide to be incorrect. -Excess post-exercise oxygen consumption (EPOC) -> More recently, EPOC was coined to replace the term ‘oxygen debt’. Terminology reflects that only around 20% elevated O2 consumption used to ‘repay’ O2 deficit.
33
What is magnitude and duration of EPOC influenced by?
Intensity of exercise
34
What are the EPOC slow and fast components?
-‘Rapid’ portion of EPOC -> Re-synthesis of stored PC in muscle (completely recovered in 60-120s). Replenishing muscle (myoglobin) and blood (haemoglobin) O2 stores. -‘Slow’ portion of EPOC -> Elevated heart rate and breathing increase O2 demand. Elevated body temperature = increased metabolic rate. Elevated blood levels of epinephrine and norepinephrine = increased metabolic rate. Conversion of lactic acid to glucose (gluconeogenesis).
35
Draw the table for fuels of exercise (carbs, fats and proteins)
In exercise metabolism notes
36
What is the estimation of fuel utilization during submax exercise and what are caveats?
-Measurement of pulmonary gas exchange provides a non-invasive technique to ‘estimate’ fuel utilization during exercise and involves measurement of respiratory exchange ratio (RER). -Caveats -> Measurement must be performed during steady-state exercise (that is below lactate threshold) to be reflective of metabolic exchange of gases in tissues. Assumes that ‘0’ protein is used as a fuel during exercise. -Oxidation of fat = 0.70 and oxidation of carbs = 1.00
37
Describe how exercise intensity and duration govern fuel selection during exercise:
-Exercise intensity -> ‘Crossover’ concept: the shift from fat to CHO metabolism as exercise intensity increases. Due to: recruitment of fast muscle fibres (abundance of glycolytic enzymes, fewer lipolytic enzymes) and increasing blood levels of epinephrine stimulate glycolysis and lactate production (inhibits fat metabolism by reducing the availability of fat as a substrate) -Exercise duration -> Due to an increased rate of lipolysis - Breakdown of triglycerides (by lipases) = glycerol + FFA. Stimulated by rising blood levels of several hormones (epinephrine, norepinephrine and glucagon)
38
Describe the interaction of fat/ CHO metabolism:
-Glycogen is depleted during prolonged (<2hrs) high-intensity exercise -> Decreased rate of glycolysis and production of pyruvate (important precursor for Krebs-cycle intermediates) and decreased rate of Krebs-cycle activity -‘Fats burn in the flame of carbohydrates’ -> Decreased Krebs-cycle intermediates also decrease the rate of fat oxidation. Fats can only be metabolized via Krebs-cycle oxidation. -Decreased amount of muscle and blood carbohydrate stores contribute to fatigue -Ingestion of sports drinks (30-60g of CHO/hr) can improve endurance performance
39
Draw the table for best exercise intensity to burn fat
-In exercise metabolism notes
40
What is the impact of exercise intensity on fat metabolism?
-FAT max -> Highest rate of fat oxidation. Reached just before lactate threshold.
41
What is the influence of exercise intensity on fuel source?
-The relative contribution of muscle glycogen and blood glucose varies as a function of the exercise intensity (and duration) -Increased rate of glycogenolysis due to recruitment of fast-twitch fibres and elevated blood epinephrine levels
42
What is the influence of exercise duration on fuel source?
-Percentage of energy derived from the four major sources of fuel during prolonged submaximal exercise (i.e. 65%-75% VO2 max), -Immediate energy sources in muscles depleted over time. -Increased reliance on substrates in the blood
43
What is lactate threshold?
-The point at which blood lactic acid rises systematically during incremental exercise -Appears at 50-60% VO2 max in untrained subjects -Occurs at higher work rates (65 to 80% VO2 max) in endurance trained subjects -Also called ‘anaerobic threshold’ -OBLA = point at which blood lactate reaches >4 mmol/L
44
What are the explanations for lactate threshold?
-Low muscle oxygen (hypoxia), therefore increases anaerobic metabolism -Accelerated glycolysis -> NADH produced faster than it is shuttled into mitochondria (exceeds transport capacity of the hydrogen shuttle mechanism). Failure of this mechanism to keep up with the rate of glycolysis results in pyruvate accepting un-shuttled H+ to form lactate. -This is independent of whether the cell has sufficient O2 -Recruitment of fast-twitch muscle fibres during intense, rapid exercise -> LDH isozyme (exact form of the enzyme) in fast fibres has a greater affinity for attaching to the pyruvate – promotes lactate formation -Reduced rate of lactate removal from the blood -> Blood flow to muscle prioritized over tissues responsible (e.g. liver) for removing lactate -Blood lactate concentration = Lactate entry into the blood – blood lactate removal
45
Describe lactate as a fuel source during exercise:
-Historically, lactate was considered to be a waste product of glycolysis with limited metabolic use -Lactate shuttle: produced in one tissue and transported to another to be used as an energy source -The cycle of lactate/ glucose between the muscle/ liver is called the Cori Cycle