Guconeogenesis Flashcards
What hormone stimulates gluconeogenesis?
glucagon (think Glucose is Gone)
What is used to make glucose when starving, low/no carbs and when you exercise?
Starvation: primarily amino acids
Low/no carbohydrates = primarily amino acids
Exercise = lactic acid alanine
What are the main non-carbohydrate precursors for gluconeogenesis?
Lactic acid
alpha keto acid
glycerol
What are the main entry points in gluconeogenesis?
Pyruvate
oxaloacetate
DHAP
What requires glucose in the body?
Brain Red blood cells Testes Medulla of the kidney Cornea of the eye Muscle (during high intensity exercise)
What is the energy requirement of the brain for glucose?
100 grams per day (400 kcal)
What is the Red blood cells need for glucose?
20 grams per day (the brain needs 5x time at 100g/day)
Where does gluconeogenesis occur?
Liver (90% of GNG)
Renal cortex
Small intestine
How is GNG made energetically favorable?
by alternative enzymes in the cytosol and mitochondria
coupled reactions
ATP
What reactions are irreversible in glycolysis?
Hexokinase (glucokinase)
Phosphofructokinase
Pyruvate kinase
(because these 3 reactions are irreversible in glycolysis we need to find another way around them for GNG)
What is the first obstacle in GNG?
Turning pyruvate into phosphoenolpyruvate (this reaction is the opposite of the last irreversible reaction in glycolysis)
What are the 2 enzymes used to get turn pyruvate into phosphoenolpyruvate? (get past the first obstacle for GNG)
Pyruvate crboxylase
PEP carboxykinase
What coenzyme does pyruvate carboxylase use?
Biotin
When does gluconeogenesis occur?
when blood glucose is low from:
starvation
not eating carbohydrates
exercise
Where can you find pyruvate carboxylase?
in the mitochondria of liver and kidney
also present in muscle but does not synthesize glucose
What does pyruvate carboxylase do in muscle?
Uses OAA produced as intermediate in Kreb’s (in liver/kidney it makes OAA)
What is the function of pyruvate carboxylase?
Turn Pyruvate into Oxaloacetate
What is the precursor for pyruvate? (the substrate that it works on)
pyruvate or alanine (remember that alanine can be turned into pyruvate by transamination)
After pyruvate carboxylase turns pyruvate into oxaloacetate, how is OAA moved into the cytosol.
Through the malate shuttle
malate dehydrogenase is used inside the mitochondria and the cytosol in the malate shuttle
What is the function of malate dehydrogenase in the malate shuttle?
In mitochondria: turn OAA into Malate
In cytosol: turn malate into OAA
In the cytosol what enzyme turns Oxaloacetate into phosphoenolpyruvate?
PEP carboxylase
During what steps is energy used in GNG for the first obstacle?
Pyruvate carboxylase uses ATP (1st step)
PEP carboxykinase uses GTP (2nd step)
Which part of the 1st obstacle of GNG does not use energy?
malate shuttle (adds or subtracts hydrogen through NADH)
What stimulates Pyruvate carboxylase?
Acetyl CoA (this is produced during FA oxidation or OHOT)
In what location will an elevated amount of Acetyl CoA stimulate Pyruvate Carboxylase?
Mitochondria
the enzyme PEP carboxykinase is dependent upon what mineral?
Mg2+
When is the only time that PEP will act in the mitochondria during GNG?
if lactate is the precursor (lactate will be turned into pyruvate first then transported into the mitochondria. Then phosphoenolpyruvate will be transported to the cytosol)
When will Lactate be present in the mitochondria?
after Anaerobic glycolysis or Erythrocyte glycolysis
What does the conversion of Lactate to pyruvate in the cytosol yield?
NADH
What is the second obstacle in GNG?
Fructose-1,6-bisphosphate
we use PFK for this reaction in glycolysis
What enzyme is used to overcome the 2nd obstacle in GNG?
Fructose-1,6-bispohsphatase
it is also Mg2+ dependent
What mineral doe Fructose-1,6-bisphosphatase require?
Mg2+
What is the third obstacle in GNG?
glucokinase (this turns glucose into glucose-6-phosphate)
What enzyme is used to overcome the 3rd obstacle?
Glucose 6-phosphatase (also Mg2+ dependent)
What enzymes are Mg dependent in GNG?
- PEP carboxykinase
2.Fructose-1, 6-bisphosphatase - Glucose-6-phosphatase
(each obstacle has an Mg2+ dependent enzyme)
Why can the l9ver release glucose?
it contains glucose-6-phosphatase (this turns G6P into free glucose which muscle does not have)
Why can’t muscle release glucose?
it does not have glucose-6-phosphatase (this enzyme turns G6P into free glucose)
Is GNG energy expensive?
yes, it uses 6 high-energy phosphate groups (4ATP and 2 GTP) and 2 NADH. (2 pyruvate are used to make glucose)
