Regulation of Enzymes in Glycolysis and Gluconeogenesis Flashcards
PDH Kinase
+ ATP, Acetyl-Coa, NADH (indicates high energy in the cell to deactivate PDH complex so acetyl-CoA is not produced.
- Pyruvate (needs to be converted to acetyl-CoA)
PDH Phosphatase
+ Ca2+ (indicates contracting muscle and a need for energy, so acetyl-CoA is needed.
Removes phosphate group from PDH complex
Pyruvate dehydrogenase complex
- by its own products, NADH and acetyl-CoA
PFK-2
Increase in BG levels = + INSULIN, which - cAMP, which - protein kinase, which dephosphorylates the bifunctional enzyme, activating PFK-2 activity, leading to production of F 2,6-bisphosphate and increase glycolysis
Fructose 2,6-bisphosphatase
Decrease in BG levels = + GLUCAGON, which + cAMP, which + Protein kinase, which phosphorylates the enzyme, activating F 2,6-bisphosphatase leading to the production of F-6-phosphate and a decrease in glycolysis
PFK-1
- ATP, Citrate
+ AMP, Fructose 2,6-bisphosphate
RATE-LIMITING STEP
Hexokinase
- Glucose-6-phosphate (its own product)
*low Km for glucose
Glucokinase
- F-6-P
+ F-1-P
*Liver only
**INDUCIBLE enzyme + INSULIN
***High Km for glucose
Pyruvate kinase
- ALLOSTERIC
+ F 1,6-bisphosphate (product of gatekeeper step) to + cAMP + protein kinase, and phosphorylation - COVALENT MODULATION via glucagon signaling
- INDUCTION (in the LIVER) by a combination of high CHO diet and high insulin levels
Fructose 1,6-bisphosphatase
- F 2,6-bisP
- AMP
PEPCK
long-term hormonal regulation + GLUCAGON = increase synthesis of PEPCK
Glucose-6-phosphatase
Long-term hormonal regulation + GLUCAGON = increase synthesis of itself
*Liver only
Citrate Synthase
- ATP
Primary regulation is the availability of its substrates (Acetyl-CoA and OAA)
Isocitrate dehydrogenase
- ATP, NADH
+ ADP, AMP, Ca2+
Alpha-ketoglutarate dehydrogenase complex
- ATP, GTP, NADH, Succinyl-CoA (its own product)
+ Ca2+
Pyruvate carboxylase
+ [acetyl-CoA in mito] due to FA oxidation
*ANAPLEROTIC REACTION (chemical reaction that forms intermediates of metabolic pathways).
Protein kinase
- INSULIN
+ GLUCAGON
How is the activity of the bifunctional enzyme different in the liver and heart?
HEART: Phosphorylation by PROTEIN KINASE occurs at a different site that +s rather than inhibits PFK-2. This produces an INCREASE rather than a decrease in F 2,6-bisP levels (which results in an increase in PFK-2 and INCREASED GLYCOLYSIS.
LIVER: the opposite of above
How is gluconeogenesis allosterically regulated?
FA OXIDATION promotes gluconeogenesis and inhibits glycolysis by: causing an INCREASE in acetyl-CoA in mito which:
a. + Pyruvate carboxylase
b. + Citrate (- effect on PFK-1 which decreases F 1,6-bisP, that - pyruvate kinase)
c. - AMP
How does glucagon and insulin regulate gluconeogenesis covalently and through induction?
+ Glucagon via covalent modulation regulates in the SHORT-TERM by glucagon: + cAMP, which + protein kinase, causing phosphorylation of the bifunctional enzyme, which - F 2,6-bisP favoring gluconeogenesis.
+ Glucagon in the LONG-TERM causes induction and increase synthesis of PEPCK and Glucose-6-phosphatase while decreasing synthesis of Glucokinase and Pyruvate kinase.
