Gluconeogenesis Flashcards
where are most of the enzymes for gluconeogenesis?
cytosol
where is pryvate carboxylase found?
mitochondria
why is the mitochondria needed in gluconeogenesis?
to use lactate, pyruvate and glucogenic aa as substrates for gluconeogenesis
Where is PEP carboxylase found?
mictochondria and cytosol
what ensures that glycolysis and gluconeogenesis won’t take place at the same time?
tight hormonal regulation
what are the irreversible steps of gluconeogenesis?
glucose 6-phosphatase
Fructose 1,6-bisphosphatase
pyruvate carboxylase
PEP carboxylase
where is glucose 6-phosphatase found
liver and kidney
where is glucose 6-phosphate generated?
gluconeogensis and glycogen degradation
what does glucogon activate at the same time?
gluconeogensis and glycogen degradation
what two pathways provide blood glucose during the first day of fasting?
gluconeogensis and glycogen degradation (most used blood glucose at beginning of fast = branched structure)
when are liver glycogen levels remarkably reduced? totally depleted?
8 hours
24 hours fo fasting
where do lactate and alanine come from
muscle
how is lactate converted to pyrvuate?
using NAD+ to make NADH and use lactate dehydrogenase
how do you convert alanine to pyruvate ?
alpha KG + glutarate
alanine aminotransferase
what are the two enzymes needed for gluconeogenesis?
pyruvate carboxylase
PEP carboxylase
how is fructose 2,6 bisphosphate formed?
by the bifunctional enzyme when the insulin/glucagon ratio is high
at high blood glucose levels, what happens to hepatic glycolysis?
favored and gluconeogenesis is inhibited
what can the bifunctional enzyme do?
form fructose 2,6 bisP using PFK-2
degrade fructose 2,6-bisP using BPase
how many proteins and how many genes does the bifunctional enzyme have?
1 and 1
insulin leads to the dephosphroylation of bifunctional enzyme and does what?
form fructose 2,6-bisP = promotes glycolysis why? - PFK-2 is active
what does glucagon do to the bifunctional enzyme?
phosphorylates it and degrades fructose 2,6 bisP and promotes gluconeogenesis –PFK-2 inactive!
what is gluconeogenesis stimulated by?
glucagon and cortisol
when liver glycogen stores are limited and once they are depleted, what is gluconeogenesis the sole provider for?
blood glucose
why are glycogen degradation and glucoenogenesis going at the same time after eating? glucagon activate
hormonal control
what inhibits gluconeogenesis in the liver?
fructose 2,6 bisP
what substrates for gluconeogenesis are found in liver?
intermediates of glycolysis, lactate in the liver, glucogenic aa
what substrates for gluconeogenesis are found in the blood?
new lactates from RBC and Cori cycle muscle
alanine and glutamine (urea cycle)
glycerol
what are the energy requirements for gluconeogenesis?
2 pyruvate
4 ATP
2 GTP
2 NADH
how many nitrogen does alanine give to the liver?
1
how many nitrogen does glutamine give to the liver?
2
what is the advantage of the Cori cycle?
allows for anerobic glycolysis in skeletal muscle and release of lactate into the blood without lactic acidosis because the lactate is used by the liver for gluconeogenesis
what happens to pyruvate in the fed state when insulin is ruling?
its substrate for PDH and acetyl coA formation goes to TCA cycle
what happens to pyruvate when glucagon is ruling in the fasting state?
pyruvate is substrate for pyruvate carboxylase – gluconeogenesis
what is the purpose of lactate in the heart?
pryruvate is formed and is substrate for the PDH and acetyl coA is used for energy metabolism
big advantage - pyruvate is formed from lactate not glucose! - therefore blood glucose is saved
since the heart always has enough ATP, what will be inhibited? why is this significant?
glycolysis and PFK-1 are inhibited by ATP
this saves glucose
heart perferes degrading fatty acids for energy - degradation of palmitate = 128 ATP!
what specific aa can be used for gluconeogenesis and inhibits (at the same time) glycolysis in the liver at the PK level?
alanine
what molecules is released during fasting into the blood and can be used donating carbon atoms for gluconeogenesis in the liver?
glycerol released from fat cells after lipolysis of the stored TAGs
what substrates are mostly used for gluconeogenesis during starvation and where do they come from?
amino acids
low insulin levels and high cortisol levels leads to protein degradation in muscle – they mainly alanine and glutaine
