Control of energy requirements of muscle Flashcards
energy flow
- sunlight provides energy
- energy trapped in organic molecules
- organisms utilise the organic molecules to obtain energy
- humans are 25% effcient
how energy efficient are humans
25% - rest is heat loss
what are the methods of providing energy to muscle without intake
- ATP is immediate fuel supply
- aerobic pathway
- anaerobic pathway
- long term stores in glycogen and TAG
muscles ATP consumption
- avidly consume ATP using actomyosin ATPase and calcium pump ATPase
- when activated, muscle metabolic rate increases more than 100-fold
- if muscles become depleted of ATP they would go into state of rigour mortis
what would happen if muscles depleted of ATP
Rigour mortis
what happens to metabolic rate of muscle when activated
increases more than 100 fold
how do muscles consume ATP
using actomyosin ATPase and calcium pump ATPase
how is rigour mortis avoided
- range of mechanisms to supply ATP accourding to needs of speed and endurance
- store lots of energy within each muscle
- range of fatigue mechanisms to ensure ATP isn’t critically depleted
PCr
phosphocreatine
what is ATP and PCr are measure of
energy turnover
what can be used to measure energy turnover
ATP and PCr
how to measure ATP and PCr
biopsy of tissue taken post exercise & rapidly frozen. then assay for
- ATP
- PCr
- Lactate
- Glycogen
problems with tissue biopsy for measuring energy turnover
- invasive
- limited points that this can be done
Alternative method of assesing ATP and PCr levels
31P NMR spectroscopy of ATP, PCr and pH
pros and cons of 31P NMR spectroscopy
pros: non invasive and measures muscle metabolism
cons: poor time resolution and limited variation of tasks
what happens to ATP levels during exercise
they fall, but not dramatically
ATP stores are sufficient for work for how long
couple of seconds
how is ATP recharged
resynthesises from ADP by:
- substrate level phosphorylation
- oxidative phosphorylation
substrate level phosphorylation
- enzyme transfers phosphate from organic P to ADP
- from phosphocreatine OR
- glucose (glycolysis&TCA)
oxidative phosphorylsation
energy from electrons pulled from organic molecules used to synthesis ATP
what is an indirect marker of muscle damage
creatine kinase (CPK)
reaction for yielding ATP from PCr
ADP + PCr + H+ -> Cr + ATP
enzyme: creatine kinase
what activates ATP synthesis using PCr
creatine kinase is always activated
a momentary rise in ADP is the stimulus for PCr hydrolysis
what is the temporal buffer for reductions in ATP
resynthesis of ATP using PCr
what does PCr buffer
ATP reductions
pH
partial buffer to move ~P from mitochondria to cross bridge
what does Pi release do
- stimulates glycolysis
- glycolysis regulates [ADP] and drives TCA
BUT
high Pi induces fatigue
what happens to muscle PCr during intermittent exercise
levels will oscillate
When does oxidate phosphorylation occur
cases of prolonged exercise
what restores PCr during recover
oxidate phosphorylation
benefit of creatine supplementation
if creatine stores increase, can increase energy store to longer than 10 seconds of vigorous exercise
- will also relate to faster recovery from aerobic exercise
2 other reactions of ADP
2ADP -> ATP+AMP
- myokinase reaction
AMP -> IMP + NH3
2ADP -> ATP+AMP
myokinase reaction
AMP is a metabolic byproduct and a stimulus
increase AMP acts as an energy crisis signal in muscle to activate AMP kinase
what is an energy crisis signal to the muscle
increased AMP - activates AMP kinase
AMP -> IMP + NH3
AMP can be deaminated giving inosine monophosphate and ammonia
together, creatine kinase and adenylate kinase act as a temporal buffer of ATP during anerobic contraction
what are the temporal buffers of [ATP] during anaerobic contraction
creatine kinase
adenylate kinase
when are creatine kinase and adenylate kinase the temporal buffers of [ATP]
during anaerobic contraction
adenylate kinase
catalysis the conversion of 2ADP to AMP and ATP
creatine kinase
catalysis conversion of ADP to ATP, using PCr
how does ATP sit in the hierarchy of energy supply
Instantly available but only in short supply
how does PCr sit in the hierarchy of energy supply
PCr rapidly produces ATP, and there is more PCr than ATP
energetic limitations of muscle power
maximum power output that human can achieve and sustain falls as the duration of effort increases
exercising for hours requires
lower power output over a long period of time
exercising for sprints requires
higher power output over a shorter period of time
method of providing energy to muscle for maintaining high rate of work once PCr supply has been exhausted
glycolysis
what is glycolysis
anaerobic process of degrading glucose or G1P to pyruvate and lactate
when does glycolysis start in exercise
immediately, but takes ~5s for max rate of ATP production tto be reached
what triggers glycolysis in exercise
increased [ADP]
what limits glycolysis
acidosis from H+ production
fatigue or Na+ depletion
storage of glucose
polymers of glucose are stored as granules of glycogen in the muscle and liver. Levels of both PCr and glycogen are manipulable by diet
Energy input and output of glycolysis
net = 2 ATP, 2NADH + 2H+
(2 pyruvate)
- investment phase needs 2 ATP from 1 glucose
- pay off phase produces 4 ATP and 2NADH
how much energy from a glucose molecule is extracted by glycolysis
2 ATP
only 10% of energy of glucose molecule. this is a pay off for convenience of supplying high power quickly
what happens to NADH and H+ produced by glycolysis
they are electron carriers that feed into mitochondria
lactate shuttle
- recruitment of TII glycolytic fibres at high exercise intensity increases lactate production
- lactate is used as fuel by the heart and oxidative skeletal muscle, and a substrate for glucose production in the liver to recreate and store energy
cori cycle
recreates and stores energy
- glycogen in the muscle undergoes glycolysis to produce lactate
- lactate travels in blood to the liver
- lactate in the liver undergoes gluceoneogenesis to produce glucose
- glucose travels in blood to muscle
presence of lactate transporters
TI slow fibres: lots of MCTI lactate transporter, has a low km of 3.5 so saturates and acts as H+ regulator for lactate uptake
TII fast fibres have lots of MCT4, with high km of 35, so act to export even high levels of lactate from muscle. Important bc TII fibres involved in lots of glycolysis
MCT4
expressed in TII
lactate transporter with high km 35mM to export lactate even at high levels
MCT1
expressed in TI
lactate transporter with low km 3.5 so saturate and act as H+ regulator for lactate uptake
how does glycolysis sit in heiracry of energy suppy
glycolysis is available fairly quickly and produces a more reasonable amount of ATP but has by products that causes acidosis which is limiting
what is the limiting factor of glycolysis
how much bodies can tolerate because of H+ produced, we cannot withstand acidosis.
CHO supply is NOT the limiting factor of glycolysis
how to provide energy to muscle for prolonged periods of work
2nd method of ATP synthesis
= TCA cycle and oxidative phosphorylation
how does TCA cycle and oxidative phosphorylation provide energy
energy from electrons pulled from organic molecules to synthesise ATP
what is the site of oxidative phosphorylation
mitochondria
where are the enzymes for beta oxidation, TCA cycle, ETC located
inside mitochondira
does TCA cycle produce lots of ATP
directly - No
Indirectly - yes, creates the environment fo oxidative phosphorylation which produces lots of energy :)
does TCA cycle require oxygen
nope
products of TCA cycle per 1 glucose
6 CO2
8 NADH + H+
2 FADH2
2 ATP
products of TCA cycle per 1 pyruvate
3 CO2
4 NADH + H+
1 FADH2
1 ATP
ATP accumulator from one glucose molecules after TCA
4
2 from glycolysis, 2 from TCA
cellular respiration reaction and energy production
Glucose + oxygen -> carbon dioxide + water
produces energy and heat
38 ATP
final step of oxidative phosphoryation
chemiosmosis
what molecular machine drives ATP synthesis in chemiosmosis
ATP synthase
where is ATP synthase
cristae of mitochondria
how does ATP synthase work
- H+ gradient provides the energy for ATP synthesis
- H+ gradient develops between IMS and matrix as electrons move along the ETC
- H+ gradient used to pump protons from the matrix to the IMS
- [H+] is the proton motive force which creates ATP from ADP and Pi
proton motive force
[H+]
where does H+ gradient develop in ETC
between IMS and matrix, with H+ moving out to IMS
IMS
inter membrane space
products of oxidative phosphorylation from one glucose molecules
3 ATP for every NADH = 10 X 3 2 ATP for every FADH2 = 2 x 2 - 6 oxygen = 34 ATP
ATP accumulator from one glucose molecules after oxidative phosphorylation
38
2 from glycolysis
2 from TCA
34 for oxidative phosphorylation
where does oxidative phosphorylation sit in the hierarchy of energy supply
happens at a limited rate but produces a very large amount of ATP
Control of cellular respiration
feedback allows for inhibitor or stimulation by key enzymes e.g:
phosphofructokinase is pH dependent and is inhibited in acidosis in order to limit glycolysis to maintain body’s pH set point
when is phosphofructokinase inhibited
acidosis
what does inhibition of phosphofructokinase do
limits glycolysis when pH id dropping to much to save from acidosis
energy provision of long duration low power exercise
fatty acids undergo beta oxidation to produce actyl coA to enter the TCA cycle to feed ETC for ATP production
where are lipid droplets for exercise fuel stored
muscle and can be regulated by diet and training
what does high lipid content in muscle mean
opposing things:
- obesity with danger of diabetes and CVD
- well trained endurance athlete
energy provided from TAG
18c FA gives 147 ATP
TAG has 3 FA = 441 ATP
+ 19 ATP from breakdown
= 460 ATP
state of lipids when stored
dry
highly hydrophobic, typical adipocyte contains 90% of its total weight as pure TAG
state of glycogen when stored
wet
hydrophilic, exists in hydrated granules and 65% of total weight is water
what is the better energy store/ CHO or fat
5 x better than CHO as energy store because of their capacity /density
how much glycogen per 1kg wet muscle
15-18g
how much intramuscular fat per 1kg wet muscle
20g
extramuscular fat stores
adipose tissue ~15kg, AKA 140,000 kcal
where does fatty acid oxidation sit in heirarchy of energy supply
happens at a very limited rate but produces a huge amount of ATP
power and capacity of anaerobic energetic processes
High power: PCr, glycolysis
Low capacity: limited supply
power and capacity of aerobic energetic processes
low power: oxidative phosphorylation and beta oxidation
high capacity: unlimited supply
respiratory exchange ratio
inform us which fuels are being used. CHO is oxidised with a RQ of 1
why is CHO RQ 1
6 molecules of oxygen are used to produce glucose, which produces 6 molecules of carbon dioxide
what is the RQ of CHO
1
what is the RQ of Fat
0.71
why is fat RQ 0.71
23 molecules of oxygen are used for fat oxidation, producing 16 molecules of carbon dioxide
what physiological function do we match to energy demand
breathing and cardiac output (HR and stroke volume)
what measure is a reflection of mitochondrial activity
VO2 and VCO2
What are VO2 and VCO2 a measure of
mitochondrial activity and they are very trainable
fuel supply in low intensity exercise
mostly FA
fuel supply in medium intensity exercise
start to use TAG and glycogen
fuel supply in high intensity exercise
lots of muscle glycogen
difference between fuel source of fit and unfit person
unfit person first burns glycogen
fit person rapidly swithes from glycogen to uses lipolysis of FA
glycogen sparing
a trained individual will burn fat preferentially when working out at the same rate as an unfit person who will burn CHO
this is an important training adaptation
how to manipulate muscle glycogen
diet and exercise
high CHO can double both glycogen stores and duration before exhaustion = basis of CHO loading
rapid, short lasting fuel supplies
PCr
slower but more abundant fuel supplies for exercise
fat oxidation
training will alter muscle metabolism to favour
fat utilisation, whilst sparing glycogen
what helps favour aerobic respiration (fat metabolism)
increase in local muscle blood supply
more mitochondria
