Week 5: Glycolysis Flashcards
What is glycolysis?
The sequence of enzyme-catalyzed reactions by which glucose is converted into pyruvate
How do we extract free energy from glucose aerobically or anaerobically?
First: Activate it by phosphorylation.
Second: Collect energy from the high-energy metabolites.
What are the 2 phases of glycolysis?
- Preparatory
2. Payoff
What step reactions are within the preparatory phase?
- Phosphorylation of Glucose
- Phosphohexose Isomerization
- 2nd Priming Phosphorylation
- Aldol Cleavage of F-1,6-bP
- Triose Phosphate Interconversion
What step reactions are in the payoff phase?
- Oxidation of Glyceraldehyde 3-Phosphate
- 1st Production of ATP
- Migration of the Phosphate
- Dehydration of 2-PG to PEP
- 2nd Production of ATP
What occurs during the phosphorylation of glucose?
Glucose phosphorylated by hexokinase to G6P
What energy molecules are used during the phosphorylation of glucose?
ATP and Mg++ shields its negative charge
What is the rationale behind the phosphorylation of glucose?
- Traps glucose inside cell by giving it a negative charge
2. Lowers intracellular glucose concentration to allow further uptake
What make the phosphorylation of glucose irreversible?
- Regulated mainly by products
- Hexokinase is allostericly inhibited by glucose-6-phosphate
- Glucokinase is activated by glucose (feedforward) and inhibited by fructose 6-phosphate
What the difference between hexokinase and glucokinase?
Hex: has a high affinity for glucose
Glu: has a low affinity for glucose
What is the purpose for glucokinase?
Plays an important role in controlling blood glucose levels since it is only active when glucose is high
Stimulates insulin release
What occurs during Phosphohexose Isomerization?
G6P is isomerized by phospohexose isomerase to F6P
What is the rationale behind Phosphohexose Isomerization?
- C1 of fructose is easier to phosphorylate by PFK
2. Allows for symmetrical cleavage by aldolase
Is Phosphohexose Isomerization reversible?
Yes
Does Phosphohexose Isomerization require Mg++?
Yes
What occurs during 2nd Priming Phosphorylation?
F6P is phosphorylated by PFK-1, ATP, and Mg+++ into Fructose 1,6-bidphosphate
What is the rationale behind 2nd Priming Phosphorylation ?
- Further activation of glucose
2. allows for 1 phosphate/3-carbon sugar after step 4
Which step would be the first committed step of glycolysis?
2nd Priming Phosphorylation by Phosphofructokinase-1
Why is 2nd Priming Phosphorylation by Phosphofructokinase-1 irreversible?
Phosphofructokinase-1 is highly regulated.
Allosterically inhibited by ATP and citrate
Allosterically activated by AMP and ADP
What occurs during Aldol Cleavage of F-1,6-bP?
Fructose cleaves into GAP and Dihydroxyacetone by aldolase
What is the rationale for Aldol Cleavage of F-1,6-bP?
- Six-carbon sugar is cleaved into two three-carbon sugars.
2. High-energy phosphate trioses
Why Aldol Cleavage of F-1,6-bP by Aldolase reversible?
Product (GAP) concentration kept low to pull reaction forward
What occurs during Triose Phosphate Interconversion?
Dihydroxyacetone isomerize to GAP by triode phosphate isomerase
What is the rationale behind Triose Phosphate Interconversion?
Allows glycolysis to proceed to payoff phase by a single chemical pathway
Why is Triose Phosphate Interconversion reversible?
GAP concentration kept low to pull reaction forward
What occurs during Oxidation of Glyceraldehyde 3-Phosphate?
GAP + Pi are catalyzed by GAP dehydrogenase and NAD+ to 1,3-bisphosphoglycerate
What is the rationale for Oxidation of Glyceraldehyde 3-Phosphate ?
- Incorporates inorganic phosphate
- Generates a high-energy phosphate compound
- Allows for net production of ATP via glycolysis
How is Oxidation of GAP reversible?
Coupled to next reaction to pull forward
What occurs during the 1st Production of ATP?
1,3-bisphosphoglycerate pairs with ADP and Mg++ to form ATP and 3-Phosphoglycerate by Phosphoglycerate kinase
What is the rationale for 1st Production of ATP?
Substrate-level phosphorylation to make ATP
What enzyme transfer phosphate groups
Kinases
What occurs during the Migration of the Phosphate?
3-Phosphoglycerate is catalyzed by phosphoglycerate mutate and Mg++ to form 2-Phosphoglycerate
What is the rationale for Migration of the Phosphate?
Generate a high-energy phosphate compound
What enzyme catalyze the migration of functional groups within the same molecule?
Mutases
What makes Migration of the Phosphate reversible?
Reactant concentration kept high by phosphoglycerate kinase to push reaction forward
What occurs during the Dehydration of 2-PG?
2-PG is dehydrated by enolase to form PEP
What is the rationale of Dehydration of 2-PG?
Generate a high-energy phosphate compound
Why is Dehydration of 2-PG reversible?
Product concentration kept low to pull forward
What occurs during the 2nd Production of ATP?
PEP + ADP is initiated by Mg++, K+ and pyruvate kinase to make ATP and pyruvate
What is the rationale for 2nd Production of ATP?
- substrate-level phosphorylation to make ATP
2. Net production of 2 ATP/glucose
What makes the 2nd Production of ATP irreversible?
- Regulated by ATP, divalent metals, and other metabolites
2. Activated by feed forward regulation by fructose 1,6-bisphosphate
What is used in glycolysis?
1 glucose, 2 ATP; 2 NAD+
What is made in glycolysis?
2 pyruvate
4 ATP
2 NADH
Why is glycolysis heavily regulated?
- Ensure proper use of nutrients
2. Ensure production of ATP only when needed
What enzyme cleaves glycogen and starch
Glycogen phosphorylase
What are components of lactose
Glucose and galactose
What are the components of sucrose?
Glucose and fructose
What occurs during fermentation?
- Generation of energy (ATP) without consuming oxygen
- Reduction of pyruvate to another product (alcohol or lactate)
- Regenerates NAD+ for further glycolysis under anaerobic conditions
What enzyme reduces pyruvate to lactate?
Lactate dehydrogenase
What is coenzyme is used for fermentation?
NADH
What is produced during aerobic glycolysis?
- Produces 2 ATP and 2 NADH
2. NADH is converted to ATP in the electron transport chain (ultimately gain 2.5 ATP per NADH)
What is produced during anaerobic glycolysis?
- Produces 2 ATP
2. 2 NADH are recycled to NAD+ by lactate dehydrogenase
