Flashcards in Lecture 26: Gluconeogenesis Deck (86)
What are the 2 main metabolic priorities of our bodies?
1. Make sure the brain has enough fuel
2. Make sure we're not breaking down to much protein in our muscles = avoiding too many AA catabolism for gluconeo
3 mechanism to maintain blood glucose levels?
2. Glycogen synthesis/breakdown
What 2 organs can perform gluconeo? % of where it happens?
1. Liver: 90%
2. Kidneys: 10%
What are the possible starting materials for gluconeo?
1. Pyruvate from lactate
2. Glycerol (small amounts during fasting state)
3. TCA cycle intermediates (which can be formed by glucogenic AAs)
How do adipocytes contribute to gluconeo?
They break down TAGs to free glycerol:
1. Can convert all the way up to DHAP but process stops there
2. Liberate a ton of it for the liver/kidneys to perform full gluconeo
How is glycerol converted to DHAP? 2 steps
1. Glycerol kinase: glycerol + ATP = glycerol-3-P + ADP (only in kidneys/liver)
2. Glycerol-phosphate dehydrogenase: glycerol-3-P + NAD+ = DHAP + NADH
What do the 3 bypasses of gluconeo accomplish?
1. Add Cs to make glucose
2. Reduce molecules to give glucose its reducing power
How much ATP does gluconeogenesis use compared to the energy created by glycolysis?
It uses up more energy than glycolysis provides (6 used vs 2 in glycolysis)
What are the 2 inhibitors of pyruvate kinase? Explain how each works.
1. Alanine: allosteric inhibition
2. Glucagon/catecholamines: cAMP/PKA phosphorylation of pyruvate kinase = decreased activity
Gluconeo Step 1: Reactant/Products? Include # of Cs.
Pyruvate (3C) + HCO3- + ATP => Oxaloacetate + ADP + Pi
Gluconeo Step 1: Reaction type? 2 answers
2. Anaplerotic because provides a TCA intermediates thereby the TCA rate
Where does the pyruvate in Step 1 of gluconeo come from?
3. Lactic acid
4. Glucogenic AAs: glutamate, aspartate among others
What are alpha keto acids? What is their purpose?
AAs without the amino group (replaced by another carboxyl group) that will feed into other pathways
How is pyruvate generated from alanine?
Alanine + alpha ketoglutarate = pyruvate + glutamate
What is the glucose-alanine cycle? 5 steps
1. Glucose converted to pyruvate in muscle
2. Pyruvate converted to alanine via aminotransferase
3. Alanine is delivered from the muscle during starvation to the liver
4. Liver converts it to glucose through gluconeo
5. Glucose goes back to muscle for protein formation and energy
What is the Cori cycle?
1. Lactate formed in muscles during anaerobic metabolism of glucose is sent to the liver
2. Liver converts it to glucose through gluconeo
3. Glucose goes back to muscle for protein formation and energy
How is lactate converted to pyruvate?
Lactate dehydrogenase: lactate + NAD+ => pyruvate + NADH
Which conversion to pyruvate is faster: AAs or lactate? Why is this a good thing?
Good to avoid muscle wasting during fasting
Gluconeo Step 1: Enzyme?
What is pyruvate carboxylase regulated by?
Acetyl CoA: high levels activate it, low levels inhibit it (allosteric regulation)
Gluconeo Step 1: Cofactors?
Gluconeo Step 2: Reactant/Products? Include # of Cs.
Oxaloacetate (4C) + NADH => Malate (4C) + NAD+
Gluconeo Step 2: Purpose?
Get oxaloacetate out of the mitosol! Malate shuttle.
Gluconeo Step 4: Reactant/Products? Include # of Cs.
Malate (4C) + NAD+ => Oxaloacetate (4C) + NADH
Gluconeo Step 3?
Malate transport from mitosol to cytosol
Gluconeo Step 5: Reactant/Products? Include # of Cs.
Oxaloacetate (4C) + GTP => Phosphoenolpyruvate (3C) + GDP + CO2
Gluconeo Step 5: Reversible or irreversible?
Where does gluconeo step 5 happen?
Can happen either in mitosol or cytosol
Gluconeo Step 5: Enzyme?
Cytosolic/Mitochondrial PEP carboxykinase