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Lecture 7

Lecture 7.odt

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University of Toronto St. George
Michael Baker

Recall: – pyruvate accumulates because not enough oxygen – muscle is not supplyed with enoughh blood- if not enough blood goes in muscle cells that mean red blood cells can't provide enough oxygen – lactate accumulates – PH drops – muscle cramping – NADH converted to NAD+ – what's the advantage of pyruvate converted to lactate with respect to glycolysis, if it can't go to mitochondria? – How is the conversion of NADH to NAD+ advantageous if you are relying on glycolysis to generateATP? True – Advantageous because – you are reducing the products (pushing the equilibrium to the right) and the NAD+ can go back in glycolysis and help generateATP – it's a substrate – most people can't convert lactate back to pyruvate – so goes back to blood and recycled in the liver – very useful fuel gone to waste Soon- yi continuatio – Soon-yi starts to run over the sand, but her existing blood glucose cannot readily sustain muscle glycolysis – she needs more fuel for glycolysis and her muscle glycogen will provide this – also needed to maintain blood glucose levels – you can go into hypoglycemia and collpase if blood sugar not maintained at 3 mM – side note – never eat and run – cramps – oxygen needed for digestion Glycogen – substantial resource of glucose – glycogen granuale can be broken down: – as a source of energy – source of blood sugar – takes a longer time to access fat than glycogen(breaks down more easily) – polymer of glucose (alpha 1-4 links primarily but could be alpha 1-6 at the branch point where the oxygen on carbon 1 connects to the ch2O6 on carbon 6) – much more branched than starch (amylopectin) – stored in muscle and liver – to supply energy for muscles to keep on running – liver supports blood sugar levels – ***can't just rely on fat storage, need glycogen to last you the entire race- why is that? Fat break down gives you energy too when it goes through mitochondrial reactions? – It's because pyruvate can make oxalocetate – Combining fuels is the best way to go- glycogen and fat Soon-yi has not eaten for 10 hours , blood sugar levels decreases, she releases two hormones into the blood – adrenaline/ epinephrine released – plays a big role in muscle contraction – released during stress or exercise – regulate breakdown of glycogen in muscles- how to acess glycogen in the muscles to keep glycolysis and contraction going in the muscles – adrenergic receptors in muscles (skeltal muscle) and heart – heart rate goes up with adrenaline – leads to elevated blood pressure = hypertension Pathway for muscles – epinephrine binds to the receptors (adrenergic receptor) on the muscle cells and actates intracellular signalling pathway – This activates Adenyl cyclase (through the whole G-protein alpha unit binding) releases cAMP fromATP – cAMP = the second messenger as adrenaline does not actually enter the cell – cAMP initiates a cascade of enzyme activation in the muscle cytoplasm- amplification effect – cAMP activates Protein KinaseA(PKA)- phosphorylates proteins at serine and threonine residues, using ATP • PKAphosphorylates phosphorylase Kinase making it active ◦ calcium ions increase in muscle cells to stimulate contraction during exercise ◦ this rise in calcium ions also activates phosphorylase kinase • Phosphorylase kinase phosphorylates glycogen phosphorylase making it active ◦ glycogen phosphorylase b (GPb) = the inactive form ◦ glycogen phosphorylase a (GPa) = the active form ◦ glycogen phosphorylase also activated by rising concentrations of Pi from the hydrolysis of ATP during exercise • GPa then attacks the glycogen chains ◦ inorganic phosphate is used by GPa to cleave the glycosidic bond • end products = alpha- D- glucose-1-phopshate • Glycogenolysis- endocrine controlled breakdown of glycogen • alpha-D-glucose-1-P eventually converted to alpha-D-glucose-6-P in the muscles via phosphoglucomutase • Now alpha-D-glucose-6-P rapidly flows into glycolysis and provides a burst of fuel for the growing energy neeeds of Soon-yi's muscles- because a lot of glucose released – In this same pathway when adrenaline is released, PKAphosphorylates glycogen synthase (the enzyme that produces muscle glycogen)- inactivating it – this allows for breakdown of muscle to continue on – same end effect as epinephrine but different targe enzymes – thus soon-yi mainly use catabolic, not anabolic patway for fuels This response is seen in muscles as well as liver glycogenolysis is regulated by – hormones – epinephrine, glucagon and insulin – calcium levels – increased due to muscle contract
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