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ATP supply 4 - Dr Webster
Clinical Medicine Final MB Part I
University of Cambridge
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How is the ATP supply maintained in a skeletal muscle fibre when it goes from rest through a period of sustained exercise?
The graph shows that when AMP concentration increases by even 0 mM, the activity of phosphofructokinase increases from 15 to 50% of the maximum.
Adenylate kinase catalyses the reaction: 2ADP ATP + AMP
As ADP concentration increases during muscle contraction, it is rapidly converted to AMP and ATP. However, [AMP] is only 2% of [ATP] at rest.
Therefore, a 10% decrease in ATP will result in a 400% increase AMP. Muscle glycolysis increases up to 1000 fold at the start of intense exercise, but it is unlikely that this increase is caused by allosteric effects alone.
Further amplification occurs because of the substrate cycle that is more sensitive to small changes in the concentration of regulatory molecules.
There are different isoenzymes of the bifunctional phoshpsfructokinase-2 and fructose-2,6- bisphosphostase.
An increase in [fructose-6-phosphate] activates PFK-2 causing an increase in concentration of fructose-2,6-bisphosphate which activates PFK-1 reinforcing the effect of an increase in [AMP]. Thus increasing glycolysis.
The final important point of regulation in glycolysis is pyruvate kinase which converts phosphoenolpyruvate to pyruvate producing an ATP in the process. Pyruvate kinase is
stimulated by fructose-1,6-bisphosphate by a ‘feed forward’ stimulation, therefore the start of the pathway can stimulate the end where ATP is produced.
The overall reaction for glycolysis is:
Glucose + 2Pi + 2ADP + 2NAD+ > 2Pyruvate + 2ATP + 2NADH + 2H+ + 2H 20
In order for more ATP to be produced NADH must be re-oxidised.
Consequently, pyruvate converted to lactate by lactate dehydrogenase regenerating NAD+ in the process.
This lactate is exported to the liver in the blood or converted back to pyruvate for oxidation of the carbon backbone in the citric acid cycle.
ATP supply 4 - Dr Webster
Module: Clinical Medicine Final MB Part I
University: University of Cambridge
