Metabolic Fates of Pyruvate- Wimmer Flashcards
what is lactic acidosis?
build up of lactate due to lack of oxygen for ETC
what is most common cause of metabolic acidosis?
lactic acid build up
what determines if pyruvate will continue with glycolysis or will become lactic acid?
NAD+ recycling
NAD needed at glyceraldehyde-3-phosphate dehydrogenase reaction
what happens to reducing equivalents in aerobic tissues?
malate or glycerol-P shuttle carry reducing equivalents to ETC
what happens to reducing equivalents in anaerobic tissues?
NADH gies reducing equivalents to pyruvate, forming lactate
catalyzed by lactate dehydrogenase
what cells are purely anaerobic?
mature RBC- lack mitochondria
where does the backup begin when tissues lack oxygen?
ETC- becomes completely reduced, so more electron carriers can’t dump reducing equivalents
NADH builds up and activates lactate dehydrogenase so reducing agents can give electrons to pyruvate
what happens to pyruvate carbons in anaerobic tissues?
lactate dehydrogenase pyruvate + NADH –> lactate + NAD
what happens to pyruvate carbons in aerobic tissues?
pyruvate dehydrogenase and TCA cycle
what is the final electron acceptor in aerobic conditions?
water (oxygen)
what is the final electron acceptor in anaerobic conditions?
lactate
how many ATP are made under aerobic conditions?
30-32 (depending on what shuttle is used)
how many ATP are made under anaerobic conditions?
2 via substrate level phosphorylation
what cells normally produce lactic acid?
RBCs and exercising muscle
what tissues are all aerobic?
brain and liver
what two ways is lactate used to aid in clearance from blood normally?
- conversion to glucose by the liver (gluconeogenesis)
- energy production- lactate–>pyruvate–>acetyl-CoA–>CO2
(also cleared by kidneys)
what are conditions that can result in lactic acidosis and can be fatal?
increased lactate production
decreased lactate use/clearance
what are symptoms of lactic acidosis?
nausea/vomitting
hyperventilation
irregular heart rate
why is hyperventilation a symptom of lactic acidosis?
blood is acidic, so CO2 in lungs is high
hyperventilation is a way to clear excess CO2
what are some possible causes of lactic acidosis?
- restriction in blood supply
- lack of oxygenation
- delayed clearance
- renal/hepatic dysfunction
- pyruvate dehydrogenase dysfunction
what do hypoxia and cyanide poisoning do?
forces anaerobic metabolism
pyruvate forced to lactate, builds up
what does cyanide poisoning do?
blocks complex 4 of ETC cycle
very quickly fatal
what form of iron does CN bind to?
Fe 3+ (does not bind to Fe 2+ in hemoglobin)
what else can lactate pyruvate be converted to?
alanine
what happens during pyruvate dehydrogenase dysfunction?
pyruvate builds up but oxygen is still present so shuttle still work
reducing equivalents formed during glycolysis can still take NADH to ETC and some aerobic metabolism can happen
not all pyruvate is forced to lactate
recoverable