Term
| Name the 3 important enzymes of GLYCOLYSIS that are irreversible. |
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Definition
| Hexokinase, Phosphofructokinase 1 (PFK-1), Pyruvate kinase |
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Term
| Why are they irreversible? |
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Definition
| Because they are highly exergonic (-delta G). Reaction is too far from equilibrium. |
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Term
| What are the 3 Bypass Reactions of Gluconeogenesis? And what do they bypass? Why are they important? |
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Definition
Bypass I = Pyruvate Carboxylase and PEPCK
Bypass II = Fructose Bisphosphatase (FBPase)
Bypass III = Glucose-6-Phosphatase (G6Pase)
They bypass Pyruvate Kinase, PFK-1, and Hexokinase reactions, respectively (Steps 10, 3 and 1)
These rxns allow for the ACTIVATION of 1 pathway while tuning OFF the other -- RECIPROCAL/INVERSE REGULATION |
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Term
| What is the optimal enzyme of glycolysis to regulate? |
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Definition
| PFK-1 because it's early on in the cycle, is irreversible, and undoubtedly is the coolest enzyme. |
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Term
| What molecules directly upregulate PFK-1 via allosteric activation? |
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Definition
AMP, ADP, and especially F-2,6-BP (Fructose-2,6-bisphosphate).
This tells the cell that it should continue glycolysis because it needs ATP. |
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Term
| What molecules INHIBIT PFK-1? |
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Definition
ATP and Citrate
This tells the cell that there is too much ATP being produced.
(Citrate can ditch the TCA cycle and transport out of the mitochondria into the cytosol!) |
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Term
| What molecules DOWNREGULATE FBPase (Fructose Bisphosphatase)? Why does this make sense? |
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Definition
AMP and F-2,6-BP INHIBIT FBPase. Makes sense b/c high levels of each say that there is too little ATP so we want to undergo GLYCOLYSIS and NOT g-neogenesis.
RECALL: that FBPase is the Stage II bypass enzyme part of Glucoeogenesis. Also know that it's a RECIPROCAL reaction of PFK-1!
Note: AMP and F-2,6-BP stimulate PFK-1! |
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Term
| What is the BIFUNCTIONAL enzyme that interconverts F6P and F-2,6-BP? |
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Definition
Liver PFK-2 and liver FBP-ase-2
They are one ENZYME.
-PFK-2 is the PHOSPHORYLATOR of F6P!
-FBPase-2 is the DEPHOSPHORYLATOR of F-2,6-BP! |
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Term
| Where is PFK-2/FBPase-2 ONLY location? |
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Definition
The LIVER!
Thus GLUCAGON can regulate it (Glucagon does not stimulate Muscle cells!!!).
Glucagon is the "Great Phosphorylator" and wants to stimulate GLUCOSE production (g-neogenesis), thus stimulating FBPase-2 activity --> G-neogenesis) |
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Term
| How is the PFK-2 domain of the bifunctional enzyme activated? |
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Definition
Active when DEPHOSPHORYLATED!!!
Recall: Insulin is the "Great Dephosphorylator". Insulin wants to get rid of Glc, thus activating PFK-2 is what we want. Since insulin is ACTIVATING PFK-2 (indirectly) a DEPHOSPHORYLATION reaction occurs to make F-2,6-BP --> activates PFK-1 |
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Term
| How is the FBPase-2 domain of the bifunctional enzyme activated? |
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Definition
| We know that this domain converts the PFK-1 activator (F2,6BP to F6P), therefore favoring Gneogenesis, thus is GLUCAGON stimulated. Glucagon is the "Great Phosphorylator" --> THUS via PHOSPHORYLATION of the FBPase-2 domain, we upregulate it. |
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Term
| What are the 3 ways to regulate an enzyme of glycolysis/g-neogenesis(from what we learned in this lecture)? |
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Definition
1. Allosteric Ligands (i.e AMP)
2. Reversible Phosphorylation (i.e. PFK-2/FBPase-2)
3. Hormonal regulation of gene expression |
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Term
| What do Pyruvate kinase, Pyruvate Carboxylase and PEPCK do? |
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Definition
Pyr Kinase - last step of glycolysis - catalyzes the IRREVERSIBLE conversion of PEP to Pyruvate, making ATP.
Pyruvate Carboxylase - an "ABC" Carboxylase (USES ATP, Biotin, and CO2) of Bypass I rxn to make OAA, ADP.
PEPCK: (4C)OAA + GTP --> (3C)PEP + GDP + (1C)CO2 |
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Term
Now, what POSITIVELY regulates Pyruvate kinase?
a. ATP
b. F-2,6,BP
c. FBP
d. acteyl-CoA
e. cAMP dependent phosphorylation |
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Definition
Pyruvate Kinase (+) Regulation
c. FBP (Fructose Bisphosphate) is CORRECT
Too much FBP (EARLIER SUBSTRATE) build up tells the cell that there are too many glycolysis intermediates, so it activates Pyr Kinase to speed it up.
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Explanation to wrong choices
All except choice E (cAMP...) are FEEDBACK INHIBITORS of Pyruvate Kinase!
A. ATP inactivates PFK-1 and Pyr Kinase!
B. F26BP activates PFK-1 and inhibits FBPase
D. Acetyl CoA INHIBITS Pyr Kinase
E. cAMP dependent phosphorylation negatively regulates Pyr kinase. (Glucagon activated --> phosphorylate PK inactivates it! --> b/c want to keep Glc) |
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Term
What is the obligate stimulator of Pyruvate Carboxylase?
A. AMP
B. Acetyl-CoA
C. F-2,6-BP
D. Insulin
E. Citrate |
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Definition
Acetyl-CoA is REQUIRED to activate Pyruvate Carboxylase, thus B is correct.
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AMP, F-2,6-BP and Insulin would all STIMULATE Glycolysis and Pyruvate Carboxylase is active in Gluconeogenesis! Btw, these do NOT inhibit the enzyme. The only way Pyr Carboxylase is inactive is if Acetyl-CoA is not present, thus Acetyl-CoA is an OBLIGATE stimulator of Pyr Kinase.
Citrate was a distractor and would actually make sense, but Citrate only inhibits PFK-1 (for this class)! |
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Term
| T/F... The rate of expression of control-point enzymes can be regulated by hormones. |
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Definition
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Term
Glucagon is
a. Pro - Glycolysis and Anti-Gluconeogenesis
b. Pro-Glyc and Pro-GNG
c. Anti-Glyc and Pro-GNG
d. Anti-Glyc and Anti-GNG
e. None of the above |
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Definition
| Glucagon wants to keep Glc levels high, thus is Pro-Gluconeogenesis and Anti-Glycolysis (Choice C) |
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Term
| How does Glucagon control the level of Glycolytic/GNG enzymes? A. Decrease Glucokinase and PFK levels and an increase in PEPCK, FBPase, and G6Pase levels B. Increase Glucokinase and PFK levels and an decrease in PEPCK, FBPase, and G6Pase levels C. Decrease Glucokinase, PFK, PEPCK, FBPase, and G6Pase levels in the cell D. Decrease Glucokinase, PFK, PEPCK, FBPase, and G6Pase levels in the cell E. Increase Glucokinase, PFK, PEPCK, FBPase, and G6Pase levels in the cell |
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Definition
A. Decrease Glucokinase and PFK levels and an increase in PEPCK, FBPase, and G6Pase levels
Explanation:
Glucagon wants to INCREASE production of Gluconeogenic enzymes and DECREASE Glycolytic enzymes in the cell to sustain high Glc levels in the blood.
Recall that Glucagon does NOT affect Muscle cells. |
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Term
What is the only enzyme of Gluconeogenesis that is hormonally controlled to decrease its cellular levels? What is the hormone that induces this downregulation?
A. PFK-1; Insulin
B. Pyruvate Kinase; Glucagon
C. PEPCK; Glucagon
D. PEPCK; Insulin
E. Glucokinase; Glucagon |
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Definition
Choices A, B, and E are wrong because they are not gluconeogenic enzymes!
That leaves C and D.
Now, what would want to decrease the levels of PEPCK? Something that would want to prevent Gluconeogenesis --> INSULIN
Thus, D. PEPCK; Insulin is correct. Recall that Glucagon would want to STIMULATE PEPCK, thus GNG --> make glc! |
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