Glycogen, Gluconeogenesis and Hexose Monophosphate Shunt Flashcards
Hallmark clinical feature of Pompe disease related with the cause of death, what is the cause of this disease?
- cardiomegaly infantile onset, death without tx at 2 yrs
- lysosomal alfa 1-4 glucosidase deficiency
Difference between Von Gierke and Hers disease?
- Von Gierke overall MORE severe (profound hypoglycemia), Hers MILD (hypoglycemia).
- Hepatomegaly and normal collagen structure - sameness
What is the cause of hyperuricemia in Von Gierke disease?
- ⬇️ Pi (“trap” in glucose 6-P) ▶️ ⬆️ AMP ▶️ Uric acid (⬆️ lactate ▶️ ⬇️ Uric acid excretion in kidney) ▶️ Gout
What are the glycogen storages disease that have inclusion or result abnormal glycogen structure?
- Cori ▶️ single glc residues outer branch, short outer branches
- Andersen ▶️ very few branches, especially toward periphery
- Pompe ▶️ glycogen-like material in inclusion bodies
Which fatty acid is the exception that can rise a gluconeogenic molecule?
- odd number carbon fatty acids ▶️ propionyl-CoA
What is the key control point in gluconeogenesis? What regulates it?
- fructose 1,6 biphosphatase
- (+) ▶️ ATP
- (-) ▶️ AMP, F 2,6-BP (control glycolysis and gluconeogenesis);
- glucagon ▶️ (-) PFK-2 ▶️ ⬇️ F 2,6-BP (+) gluconeo
- insulin ▶️ (+) PFK-2 ▶️ ⬆️ F 2,6-BP (-) gluconeo
Why the skeletal muscle doesn’t have glucose 6 phosphatase?
- muscle glycogen cannot serve as a source of blood glucose
- it’s only in the liver
HOW the B-oxidation of fatty acids contribute to gluconeogenesis besides the energy given as ATP/GTP?
- produce acetyl-CoA
▶️ (+) Pyruvate carboxylase (go on gluconeo)
▶️ (-) PDH (avoid conversion of pyruvate, and use it for gluconeo)
What kind of fuel can give rise acetyl-CoA from fatty acids since that can’t be converted to glucose?
Ketone bodies - alternative fuel, ex; Brain
WHY the B-oxidation of fatty acids contribute to gluconeogenesis besides the energy given as ATP/GTP?
- between meals ▶️ 🔛 gluconeo and (-) PDH to prevent lactate and alanine ▶️ acetyl CoA, need them as pyruvate only.
- well fed state ▶️ ⬆ acetyl CoA ▶️ cytoplasm to do FA, need OAA for this. Same acetyl CoA (+) pyr carboxylase to form it from pyruvate.
In liver and skeletal muscle what regulates the glycogen synthase?
- insulin (+) both tissues
- glucagon, epinephrine (-) liver
- epinephrine (-) skeletal muscle
What is the cori cycle?
Lactate (from RBC and muscle during exercise) ▶️ glucose (return to RBC and muscles), through gluconeo in liver
What is the alanine cycle?
Muscle release Alanine ▶️ pyruvate (gluconeo) and NH3 (urea)
Why alcoholism lead into hypoglycemia?
⬆️⬆️ NADH by alcohol DH and acetaldehyde DH to metabolize etanol:
- ⬆️ lactate from pyruvate
- ⬆️ malate from OAA
- ⬆️ glycerol 3-P from DHAP
- deviate gluconeo substrates from the pathway
Why after extreme exercise a high alcohol consumption can lead metabolic acidosis and hypoglycemia?
To realize gluconeo NAD is needed to lactate ▶️ pyruvate; it’s gone used in etanol metabolism, stay ⬆️ lactate ▶️ acidosis and hypoglycemia
What could be the mechanism to produce lipid accumulation in alcoholic liver disease?
⬆️⬆️ NADH (B-oxidation very slow) and ⬆️ glycerol 3-P + FA coming from adipose ▶️ store TG in liver
Functions of NADPH in liver, RBC, neutrophils
- liver ▶️ biosynthesis
- Neutrophils ▶️ bactericidal activity
- RBC ▶️ protect against ROS (helping supplying reduced glutathione)
Why in Glucose 6-P DH deficiency is not impair the synthesis of pentoses? What enzyme is involved?
- because there is a Shunt that allow convert glycolysis intermediates (fructose 6-P, glyceraldehyde 3-P) directly without G6PDH reaction into Ribose 5-P.
- Transketolase (TPP require)
How could you differentiate (differential Dx) between G6PDH deficiency (mutation that reduce activity less than 5%) and chronic granulomatous disease?
- Differential Dx ▶️ hemolytic anemia (may be chronic) and Heinz bodies
- both predispose an impair ability to kill microbes:
- CGD ▶️ NADPH oxidase deficiency
- G6PDH def ▶️ ⬇️ NADPH ▶️ NADPH oxidase doesn’t work
How is regulated the glycogen phosphorylase in liver and muscle?
- liver: epinephrine, glucagon (+), insulin (-)
- muscle: epinephrine, AMP, Ca (through calmodulin) (+), insulin, ATP (-)
Why G6PDH deficiency confer protection against malaria?
Accumulates ROS in RBC (target of malaria) ▶️ plasmodium deficient in antioxidant mechanism
What substances regulate G6PDH?
- NADP, insulin (+)
- NADPH (-)
Making conclusion, what substrate can control (as an axis) both gluconeogenesis and glycolysis?
Fructose 2,6 bisphosphate
