GLUCONEOGENESIS Flashcards
what is gluconeogenesis
- Conversion of non carbohydrates to glucose (or glycogen)
- MAKING GLUCOSE
Where does it occur?
- Liver (and kidney to a lesser extent) - no other tissues can do it (as they don’t express enzymes that you need)
- Cytosol, mitochondria and smooth endoplasmic reticulum
- express all 4 obligatory enzymes for gluconeogensis at same time*
Functions og gluconeogensies
-Maintains glucose when dietary carbohydrates are low in supply
- Maintains TCA cycle intermediates
- Clears metabolites from blood (ie lactate, glycerol, propioate)
why are ruminants and big cats dependent on gluconeogenesis
- In ruminants, the carbohydrates in the diet are fermented to volatile fatty acids (VFA) in the rumen by the action of microbes.
- Therefore, ruminants do not absorb much glucose under normal dietary conditions.
- Gluconeogenesis is essential at all times in ruminants for the glucose homeostasis.
- In the well-fed ruminant, glucose is derived from the conversion of propionate (a C3 fatty acid) to
carbohydrates from their diet.
obligate carnivores do not absorb carbs from diet really
- These species too are dependent on gluconeogenesis from amino acids for their glucose supply.
- During starvation, gluconeogenesis is the basis for long-term glucose homeostasis for all mammalian species.
When is gluconeogenesis needed
- Long term glucose homeostasis (commences after 12 hours of limited glucose intake)
- Animals that absorb little glucose
- well fed ruminants and pseudo-ruminants -> ferment carbs, make fatty acids, must make glucose from them -> absorb little glucose from diet - horses on roughage diets
- cats (obligate carnivore) -> lots of proteins, not carbs
- All starving animals -> STARVATION
when is glycolysis considered irreversible back into gluconeogenesis
- when pyruvate turned into
WHAT are the obligatory quartet enzymes?
- Pyruvate carboxylase - mitochondrial
- Phosphoenolpyruvate CarboxyKinase (PEPCK) - mitochondrial and cytosolic; varies between species
- Frutose 1,6-bisphosphatase - cytosol
- Glucose 6-phosphatase - smooth endoplasmic reticulum
Obligated to have them to do gluconeogenesis as needed to reverse irreversible steps of glycolysis
What are Non-carbohydrate gluconeogenic substrates
- carbon from non carbohydrate sources
1. Lactate -> back to pyruvate
From muscle (anaerobically) and erythrocytes
2. Gluconeogenic amino acids - From protein catabolism (high protein diets or from muscle during starvation)
3. Glycerol - From adipose tissue (don’t confuse with fat)
4. Propionate - From carbohydrate digestion in ruminants (major gluconeogenic substrate in fed ruminants)
how is gluconeogenesis regulated?
- Change in rate of enzyme synthesis (takes hours) -> slow - Insulin (glycolytic enzymes)
- Adrenalin/glucagon (gluconeogenic enzymes) - Covalent modification -> add phosphate to
- Allosteric effects
What regulates the enzymes of gluconeogenesis
- Pyruvate Carboxylase
allosteric enzyme; acetyl CoA is stimulator - Phosphoenolpyruvate Carboxykinase induced by glucocorticoids
- Fructose 1,6-bisphosphatase
major control allosterically regulated by F 2,6 bisP - Glucose 6-phosphatase
essential for the release of glucose from the liver cell into the hepatic vein
What is glucagon and Where is glucagon released
- hormone that signals the liver to increase blood glucose supply (release glucose during starvation)
- signals gluconeogenesis
- released from alpha cells of pancrease when low glucose levels
where are glucagon receptors found
- liver and adipose
- NOT MUSCLE
what effect does insulin have on gluconeogenesis?
inhibits the enzymes needed
What does glycogen do to regukate glycolysis and gluconeogensesis during starvation?
- stimulates cAMP dependent protein kinase -> phosphorylates pyruavate kinase which usually makes pyruvate in glycolysis -> this inhibits glycolysis
- also stimulates gluconeogenesis when needed via inhibiting fructose 2,6 bisphosphate
What does Frucpse 2,6 BisPhosphate do to regulate glycolysis and gluconeogenesis during starvation
- powerful allosteric affector -> bifunctional -> stimulates PFK2 which stimulates PFK1 (glycolysis) and inhibits fructose 2,6 biphosphatASE to inhibit gluconegenesis
- if gluconeogenesis needed (starving), glucagon will bind, switch on cAMP dependent protein kinase which will phosphorylate PFK 2 -> means that fructose 2,6 bisphosphtASE is working and stimulates gluconeogenesis.
- This will mean glycolysis cannot occur because PFK 2 doesn’t stimulate PFK 1 and thus no glycolysis
how does adrenalin regulate glycolysis and gluconeogenesis during starvation
does exact same seps at glucagon -> cAMP -> pyruvate kinase inhibited, inhibits fructose bisphosphate and PFK 2 = no glycolysis
how does insulin regulate glycolysis and gluconeogenesis when body well fed?
- binds to receptor and stimulates phosphodiesterase -> this breaks down cAMP -> no cAMP dependent protein kinase made -> cannot phosphrylate pyruvate kinase or PFK 2 = gluconeogenesis inhibited, glycolysis activated
- also causes increased uptake of glucose into cells -> causes increased fructose 6-phosphate (allosteric effector) -> speeds up fructose 2,6 bisphosphate enzyme = stimulates glycolysis (PFK2 to PFK 1), fructose 2,6 bisphosphatase inhibited = gluconeogeness inhibited
glucose homeostasis main functions during short term fed, short term starving, mdeium term starving and during exercise
- Short term - just fed (day 1)
- Emphasis on storage of excess glucose as glycogen and excess carbon as fat
- Driven by insulin - Short term shortage
- Emphasis on mobilisation of glycogen stores
Driven by glucagon - Medium term - starvation (2 days on)
Emphasis on glucose sparing
Gluconeogenesis for glucose dependent tissues
Driven by glucagon - High demand - stress/exercise
Emphasis on maximising glucose availability
Driven by adrenalin
