Gluconeogensis Flashcards
why is gluconeogenesis important?
helps the body maintain glucose levels during fasting
what does gluconeogenesis use to make glucose?
amino acids, lactate, and glycerol
where does gluconeogenesis occur?
mainly the liver (could also be epithelial cells in kidney or intestine
Fasting, where do we get glucose?
1) glycogen stores (12-24 hours) until we run out
2) gluconeogenesis (kicks in 12 hrs in as main provider of glucose)
gluconeogenesis
uses ATP to turn pyruvate into glucose
which glycolysis reactions are irreversible?
1, 3, and 10
sources of pyruvate for gluconeogenesis (1)
lactate (lactate dehydrogenase takes Hydrogen from lactate and makes it pyruvate while making NADH)
sources of pyruvate for gluconeogenesis (2)
amino acids (alanine) alanine comes from breakdown of protein and skeletal muscle cells alanine transaminase (vitamin B6 as a cofactor) removes amino from alanine and turns it to pyruvate
during fasting,
pancreas senses low glucose, releases glucagon
there is also low insulin, high epinephrine
gluconeogenesis step 1A
1) pyruvate enters mitochondria
2) pyruvate carboxylase adds a carbon to it creating oxaloacetate
carboxylase enzymes require what cofactors
ABC
ATP
Biotin
CO2
gluconeogenesis step 1B
- we need oxaloacetate out of mitochondria and into the cytoplasm
1) malate dehydrogenase adds Hydrogen to oxaloacetate making malate
2) malate can exit mitochondria and get into cytoplasm where malate dehydrogenase converts it back into oxaloacetate
gluconeogenesis step 1C
oxaloacetate to phosphoenolpyruvate
enzyme: PEPCK removes a carbon and adds a phosphate
requires GTP
PEPCK regulation
stress hormones: glucagon, epinephrine, and cortisol enhance PEPCK by induction
gluconeogenesis 2nd roadblock
PEP to DHAP
using glycerol
- glycerol can make DHAP
- glycerol kinase adds phosphate from ATP to C3 on glycerol
- makes glycerol-3-phosphate (G3P)
- glycerol-3-phosphate dehydrogenase converts G3P to DHAP
gluconeogenesis 3rd roadblock
PFK1 rxn
in gluconeogenesis, fructose 1,6 bisphosphatase removes phosphate from C1 of fructose-1,6-bisphosphate making fructose-6-phosphate
rate limiting step of gluconeogenesis
fructose-1,6-bisphoshatase
up-regulation of gluconeogenesis
when liver burns a lot of fat making a lot of ATP
high ATP = enhances fructose-1,6-bisphosphatase
fructose-1,6-bisphosphatase regulation
glucagon activates, insulin inhibits
final step of gluconeogenesis
glucose-6-phosphate to glucose
enzyme: glucose-6-phosphatase
- once phosphate is removed, glucose can enter bloodstream
high levels of alcohol (ethanol)
- processed in liver
- cause increase in NADH and ATP
high NADH causes
lactate, malate, and G3P dehydrogenase enzymes in gluconeogenesis to go the reverse way
impairs gluconeogenesis!
causes low blood sugar when fasting
