Anaerobic Metabolism During High Intensity Exercise
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Transcript of Anaerobic Metabolism During High Intensity Exercise
Anaerobic Metabolism During Anaerobic Metabolism During High Intensity ExerciseHigh Intensity Exercise
Various Roles for Anaerobic Various Roles for Anaerobic MetabolismMetabolism
Essential when the demand for ATP is greater than can be provided by aerobic metabolism
At the onset of high-intensity exercise
At maximal O2 consumption
The onset of High Intensity The onset of High Intensity ExerciseExercise
Anaerobically derived ATP may contribute 80-90 % of the total
– O2 is in short supply until cardiovascular system can meet demands
Near Maximal ONear Maximal O22 Uptake Uptake
Near maximal O2 uptake, increases in workload elicit greater contribution from anaerobic sources
– Since aerobic metabolism is maximal, the only other source of ATP is from non-oxidative sources
Anaerobic Contribution Anaerobic Contribution Decreases as Exercise Decreases as Exercise
ProgressesProgresses30 s
– 80 % anaerobic/20 % aerobic
60-90 s
– 45 % anaerobic/55 % aerobic
120-180 s
– 30 % anaerobic/70 % aerobic
Insert fig 1.2Insert fig 1.2
Insert Fig 1.1Insert Fig 1.1
Sources of Anaerobic ATPSources of Anaerobic ATP
CP or PCr degradation
Endogenous ATP
Glycolysis
PCr DegradationPCr Degradation
Creatine PhosphoKinase
PCr + ADP + H+ ATP + Cr
GlycolysisGlycolysis
Glycogen + 3 ADP + H+3 ATP + 2 lactate + 2 H+
– Can use this relationship to determine ATP provision from glycolysis during intense exercise
– Take a post exercise muscle biopsy and multiply [La+] by 1.5 Must also take into account lactate that leaves muscle
Adenosine PhosphorylationAdenosine Phosphorylation
Adenylate Kinase
2 ADP ATP + AMP
• creates an ATP, but also leaves an AMP
DeaminationDeamination
AMP + H+ IMP + NH4+
AMP Deaminase
• Conversion of AMP to IMP is irreversible
• Prevents buildup of AMP
• in conjunction with Adenylate Kinase prevents accumulation of ADP
[ATP]/[ADP] Ratio[ATP]/[ADP] Ratio
Important because it determines free energy
Hi [ATP]/[ADP] allows ATP to be converted to ADP more easily– If this happens, there is more free energy
Lo [ATP]/[ADP] – ATPADP more difficult
– Less free energy
How do you keep the ratio How do you keep the ratio high?high?
Keep making ATP from ADP
Also, Adenylate Kinase
– ADP + ADP ATP + AMP
– But AMP can go back to ADP
SoSo
Deamination converts ADP to IMP and removes loitering ADPs
Adenylate Kinase and AMP deaminase work together to prevent AMP and ADP buildup
Why do we want to keep ratio Why do we want to keep ratio high?high?
To maintain control of energy flow
We must generate ATP, but if ADP or AMP accumulate we lose control of metabolism
Timing of Anaerobic PathwaysTiming of Anaerobic Pathways
Traditional “Serial Metabolism”Traditional “Serial Metabolism”
PCr degradation immediate and only source of ATP supply in first 10 s
When PCr depleted glycolysis begins
No overlap of two pathways
Recent evidence argues against this
PCr DegradationPCr Degradation
PCr degradation is indeed instantaneous
Biopsies after 1.28 s of electrical stimulation show PCr breakdown
Glycolysis Also InstantaneousGlycolysis Also Instantaneous
Elevated [La+] reported after 10 s cycling 110 % VO2max
Although no resting sample taken (Saltin et al., Jacobs et al.)
Other studies have shown [La+] after only 6 s, and PCr stores were not depleted after 6 or 10 s
Rates of Anaerobic Rates of Anaerobic MetabolismMetabolism
Anaerobic ATP must be provided at very high rate
Power outputs of 2-4 times VO2max can be attained for short periods
Even though anaerobic pathways provide less ATP per mole of substrate than oxidative pathways
Insert Table 1.2Insert Table 1.2
Rate ContinuedRate Continued
0-10 s - ~6.0 – 9.0 mmol ATP/kg dm/s
– Combined for PCr and glycolysis
30 s – PCr ~ 1.6 and glycolysis ~4.4 mmol/kg dm/s
– Assuming 25 % releas of lactate, ~5.8 for glycolysis
Insert fig 1.4Insert fig 1.4
Take HomeTake Home
Highest rates of ATP provision from PCr and glycolysis 0-10 s
From 10 – 30 s PCr stores are depleted
– Glycolytic rate ~ 50 % of intitial 10 s
– Glycolytic rate of ATP provision during 30s maximal exercise, 3-4 times > PCr
Direct Measurement of Direct Measurement of Anaerobic ATP ProvisionAnaerobic ATP Provision
Insert Table 1.3
Problems Associated with Measuring Problems Associated with Measuring Anaerobic ATP ProvisionAnaerobic ATP Provision
Must take pre and post-exercise biopsies
Must account for lactate release from muscle
– Arterial and venous blood sampling
– If not, exhaustive exercise or….
– Spriet et al. and closed circulation
GlycolysisGlycolysis
During intense exercise bouts ~3 min, glycolysis provides ~ 80 % total anaerobic ATP
Glycolysis is activated more quickly than aerobic metabolism – provides ATP at a higher rate
Can provide more ATP than PCr degradation
Glucose from where?Glucose from where?
Glucose can come from blood or glycogenDuring short-intense exercise, primarily
from glycogenUptake of glucose cannot meet glycolytic
demand
GLUT proteinsGLUT proteins
RegulationRegulation
Accumulation of G-6-P inhibits glucose phosphorlation
Primary points of regulation are PHOS and PFK
Why does G-6-P inhibit glucose Why does G-6-P inhibit glucose phosphorylation?phosphorylation?
Low level of glycolytic flux– Glycolysis isn’t moving very fast– Must not need G-6-P
That glucose can be stored as glycogen instead of being utilized for glycolysis
PHOS regulationPHOS regulation
PHOS = glycogen phosphorylase
The enzyme responsible for breakdown of glycogen to glucose
Removes one glucose at a time by adding Pi (phosphorylating)
Insert fig 12.2 from HoustonInsert fig 12.2 from Houston
PHOS cont’dPHOS cont’d
Km of PHOS for glycogen very low (1-2 mM)
– Means that PHOS has high affinity for glycogen
This means PHOS can function effectively even at low glycogen concentrations
More PHOSMore PHOS
Previous exercise can affect glycogenolytic rate relative to glycogen concentration
For example during afternoon practice following morning practice..
– If glycogen stores are low, glycogenolysis will be reduced
– Higher glycogen stores will result in higher relative glycogenolysis
Insert fig 1.5Insert fig 1.5
Pi and PHOS regulationPi and PHOS regulation
Phosphorylation of PHOS (pretty redundant eh?) results in conversion of forms
– b is inactive form
– a is active form
– Phosphorylation converts b form to a
Implications for activity???
At rest 10-20% of PHOS in a form
Conversion from b to a doesn’t necessarily mean increased glycogenolysis
Free Pi also needs to be available for elevated glycogenolysis to occur
Calcium activates PHOS Calcium activates PHOS kinasekinase
Phosphorylation of PHOS (again) results from PHOS kinase
PHOS kinase activated by elevations in intracellular [Ca2+]
Why would you want to tie PHOS to Why would you want to tie PHOS to intracellular [Ca intracellular [Ca 2+2+]??]??
With E/C coupling Ca2+ released from sarcoplasmic reticulum
Intracellular [Ca2+] elevated drastically and rapidly
Therefore glycogenolysis is tied closely to muscular contraction
Acidosis hinders PHOS acitivity Acidosis hinders PHOS acitivity
Conversion of PHOS b to a is depressed under acidic conditions
After repeated bouts of interval cycling, decreased activation of glycogenolysis related to increasing muscle acidity (Spriet et al.)
Although activity was still reduced in a second bout 1 hour after the first, where H+ had recovered
Phosphofructokinase (PFK) Phosphofructokinase (PFK) regulationregulation
Most important regulator of PFK activity is ATP
ATP can bind to PFK at two sites and alter its activity
Binds to catalytic site with high affinity
Can also bind to allosteric site
PFK cont’dPFK cont’d
Binding to the allosteric site inhibits activity
So,… when [ATP] in the cell is high, PFK will be inhibited– no need for glycolysis, plenty of ATP
H+ can enhance ATP affinity for allosteric site– Provides feedback inhibition
Some other proposed Some other proposed modulatorsmodulators
Inhibitors
– Citrate
– Phosphoglycerate
– Phophoenolpyruvate
– Mg2+
Promoters
– AMP and ADP
– Pi
– NH4+
– Fructose –2,6 diphosphate
CitrateCitrate
Probably not a major factor during short, intense exercise
Aerobic metabolism does not contribute greatly until later (>30 s)
Citrate probably does not accumulate within the 30-60 s time frame
PromotersPromoters
ADP and AMP will accumulate rapidly at the onset of anaerobic exercise
– Breakdown of PCr
H+ may be reduced at the onset of exercise
– Removing the ATP induced inhibition
ConclusionConclusion
PFK regulation is obviously a complicated matter
During exercise many of the promoters (ADP,AMP, Pi, and NH4+) will accumulate
ATP will be reduced, but H+ should also rise
There may be unidentified factros which help maintain the awkward balance of promotion and inhibition during intense exercise