4_1Gluconeogenesis Flashcards
What are the 4 main regulation points of glycolysis?
1) GK, 2) PFK1, 3) F(2,6)bPase/PFK2, 4) PK, 5) PDH
What function of PFK2/F26bPase is functional with phosphorylation?
F26bPase
What is the active form of PFK-2?
dephosphorylated
What is the active form of F26bPase?
phosphorylated
What is the active form of PK?
phosphorylated
What is the active form of PDH?
dephosphorylated
What are the glycolytic enzymes?
1) GK, 2) PGI, 3) PFK1, 4) Aldolase, 4) tpi, 5) G3PDH, 6) PGK, 7) PGM, 8) Enolase; 9) PK; initation of TCA = PDH
What glycolytic steps require energy?
1, 2, 6, 7, 10
What glycolytic steps are regulated?
GK, PFK-1, PK, PDH (1, 3, 10+) and PFK2
What is the key regulatory enzyme in glycolysis?
pfk1
How is GK regulated?
induced by insulin; high Km for glucose; cannot do reverse;;; also inhibited by G6P directly
How is PFK-1 regulated?
allosterically + (AMP, ADP, F26bP), allosterically - (ATP, citrate)
How is F26bPase regulated?
inhibited by F2,6bP and AMP
How is PK regulated?
activated by phosphorylation and F16bP; inhibited by Ala and ATP
What are the non-reversible steps of glycolysis?
GK, PFK1, PK
What gluconeogenetic enzyme replaces PK?
PC and PEPCK
What gluconeogenetic enzyme replaces PFK1?
FBPase
What gluconeogenetic enzyme replaces GK?
G6Pase
What are the 4 key UNIQUE regulatory enzymes of gluconeogenesis?
PC, PEPCK, F16bP, G6Pase
Where is PEPCK located?
mitochondria or cytosol
Where is PC located?
in mitochondria
How is stress gluconeogenesis triggered?
cortisol and epinephrine
What factors stimulate gluconeogenesis?
1) prolonged exercise; 2) high protein diet; 3) stress
How is gluconeogenesis regulated (in general)?
1) by availability of substrate, 2) by key enzymes
What is the energy cost per mole of glucose?
12 ATP
What are the energy requiring steps in gluconeogenesis and how much?
1) PC = 2 ATP; 2) PEPCK = 2 GTP; 3) PGK = 2 ATP; 4) G3PDH = 2 NADH
How many ATPs = 1 NADH?
3
How is PDH regulated?
allosterically + (pyruvate, CoASH, NAD+); allosterically - (acetyl-CoA, NADH); by kinase (kinase activated by acetyl-CoA, NADH, ATP); by phosphatase (activated by Ca++)
How is PC activated?
by acetyl-CoA
How is PEPCK activated?
induced when needed via GCG cAPK pathway
How is F16bPase (FBP) regulated?
inhibited by F26bP and AMP; activated in their absence!; also induced via transcription
How is G6Pase regulated?
reacts to the increased G6P that inhibits GK; not regulated otherwise
Describe the PC mechanism.
1) ATP + COOH form phosphoanhydride, then de-CO2; 2) CO2-biotin, then decarboxylation; then biotin activates pyruvate for attack on CO2
What is the PC reaction?
pyruvate + CO2 – OAA
What is the PEPCK reaction?
OAA + GTP – PEP + GDP
What are the ways that OAA can cross mito membrane to cytosol?
1) as malate (when NADH needed in cytosol); 2) as ASP; 3) as PEP from PEPCK
What is the mechanism of the PEPCK reaction?
concerted de-CO2 of OAA and phosphorylation from GTP
