MODULE 9: Chapter 9.3 Flashcards
What is glycolysis?
Glycolysis is a core metabolic pathway that converts glucose to pyruvate, generating ATP under anaerobic conditions.
It consists of 10 enzymatic reactions and occurs in the cytosol.
What are the three primary reasons glycolysis is significant?
- Glycolytic enzymes are highly conserved among all living organisms
- It is the primary pathway for ATP generation under anaerobic conditions
- Metabolites of glycolysis serve as precursors for many interdependent pathways
This includes mitochondrial ATP synthesis.
What does glycolysis accomplish for the cell?
Glycolysis generates ATP and produces pyruvate, which can be converted to acetyl-CoA, lactate, or ethanol.
This is critical for energy production, especially in anaerobic conditions.
What is the overall net reaction of glycolysis?
Glucose + 2 NAD⁺ + 2 ADP + 2 Pi → 2 Pyruvate + 2 NADH + 2 ATP + 2 H₂O.
This reaction involves the conversion of one molecule of glucose into two molecules of pyruvate.
What are the key enzymes in glycolysis?
- Hexokinase
- Phosphofructokinase-1
- Pyruvate kinase
Each enzyme plays a critical role in specific steps of the glycolytic pathway.
How is hexokinase regulated?
Hexokinase is feedback inhibited by glucose-6-P.
This regulation helps control glucose phosphorylation.
What activates phosphofructokinase-1?
AMP and fructose-2,6-bisphosphate activate phosphofructokinase-1.
It is inhibited by ATP and citrate.
What is the significance of pyruvate kinase?
Pyruvate kinase catalyzes the final reaction in glycolysis and is activated by AMP and fructose-1,6-bisphosphate.
It is inhibited by ATP and acetyl-CoA.
What is the role of glycolysis in blood glucose levels?
Glycolysis helps maintain appropriate blood glucose levels.
A deficiency in glucokinase can lead to MODY2 diabetes.
What is the ATP yield from glycolysis under anaerobic conditions?
Glycolysis yields 2 net ATP molecules from one molecule of glucose.
This is significantly lower than the yield from aerobic respiration.
What happens to pyruvate under aerobic conditions?
Pyruvate is oxidized to CO2 and H2O in the mitochondrial matrix, generating an additional 30 molecules of ATP.
This contributes to a total of 32 ATP from one glucose molecule.
What are the two stages of glycolysis?
- Stage 1: ATP investment (reactions 1–5)
- Stage 2: ATP earnings (reactions 6–10)
These stages highlight the initial investment of ATP and subsequent production of ATP.
What is the first step of glycolysis?
Hexokinase phosphorylates glucose to form glucose-6-phosphate.
This step requires ATP.
What reaction does aldolase catalyze in glycolysis?
Aldolase catalyzes the cleavage of fructose-1,6-bisphosphate into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.
This is a key step in converting a six-carbon molecule into two three-carbon molecules.
What is substrate-level phosphorylation?
Substrate-level phosphorylation is the direct production of ATP by transferring a phosphoryl group from a high-energy donor to ADP.
This occurs in glycolysis during specific reactions.
Which enzymes in glycolysis have large negative ΔG values?
- Hexokinase
- Phosphofructokinase-1
- Pyruvate kinase
These reactions are considered irreversible under physiological conditions.
What is the significance of the ΔG values in glycolysis?
The ΔG values help identify critical steps in the pathway that drive product formation.
Large negative values indicate irreversible reactions.
What type of reactions are primarily involved in glycolysis?
Glycolysis involves bond rearrangements, phosphoryl transfer reactions, isomerizations, an aldol cleavage, an oxidation, and a dehydration.
These reactions contribute to the overall conversion of glucose to pyruvate.
What is the first reaction in glycolysis?
Phosphorylation of Glucose by Hexokinase or Glucokinase
What product is generated from the phosphorylation of glucose?
Glucose-6-P
Which enzymes catalyze the phosphorylation of glucose?
- Hexokinase
- Glucokinase
What is the role of Mg2⁺ in the phosphorylation reaction?
It shields negative charges in the ATP molecule
How does hexokinase differ from glucokinase?
- Hexokinase: found in all cells, broad substrate specificity
- Glucokinase: present only in liver and pancreatic cells, highly specific for glucose
What inhibits hexokinase activity?
Glucose-6-P
What is the second reaction in glycolysis?
Isomerization of Glucose-6-P to Fructose-6-P by Phosphoglucoisomerase
What type of reaction is catalyzed by phosphoglucoisomerase?
Interconversion of an aldose and a ketose
What is the free energy change for the isomerization of glucose-6-P to fructose-6-P?
ΔG = -2.9 kJ/mol
What is the third reaction in glycolysis?
Phosphorylation of Fructose-6-P to Fructose-1,6-BP by Phosphofructokinase-1
What is the significance of the reaction catalyzed by phosphofructokinase-1?
It serves as a major regulatory site in the pathway
What is the free energy change for the phosphorylation of fructose-6-P?
ΔG = -18.8 kJ/mol
What regulates phosphofructokinase-1 activity?
- AMP
- ADP (positive effectors)
- ATP (negative effector)
What is the fourth reaction in glycolysis?
Cleavage of Fructose-1,6-BP into Glyceraldehyde-3-P and Dihydroxyacetone-P by Aldolase
What does the term ‘lysis’ refer to in glycolysis?
Splitting
What is the mechanism of aldolase in the cleavage reaction?
Formation of a covalent enzyme–substrate complex through a Schiff base
What are the products of the cleavage of fructose-1,6-BP?
- Glyceraldehyde-3-P
- Dihydroxyacetone-P
What is the fifth reaction in glycolysis?
Isomerization of Dihydroxyacetone-P to Glyceraldehyde-3-P by Triose Phosphate Isomerase
What problem does the production of dihydroxyacetone-P create?
Only glyceraldehyde-3-P is the substrate for the next reaction
What occurs in stage 1 of glycolysis?
ATP investment and production of phosphorylated compounds
What is the net ATP yield from glycolysis after stage 1 and stage 2?
2 ATP per glucose
What is the main outcome of stage 2 of glycolysis?
ATP earnings through substrate-level phosphorylation
What is the sixth reaction in glycolysis?
Oxidation and Phosphorylation of Glyceraldehyde-3-P to Form 1,3-Bisphosphoglycerate by Glyceraldehyde-3-P Dehydrogenase
What is required for the glyceraldehyde-3-P dehydrogenase reaction to proceed?
A constant supply of NAD⁺
What happens to NADH produced in glycolysis under anaerobic conditions?
It is oxidized by lactate dehydrogenase to form lactate
What is the final product of glycolysis?
Pyruvate
True or False: Reaction 10 in glycolysis is reversible.
False
Fill in the blank: The difference between ΔG°′ and ΔG values indicates the ________ of a reaction under cellular conditions.
favorability
What two high-energy phosphoryl compounds are required for gluconeogenesis?
ATP and GTP
What is the product of the oxidation and phosphorylation of glyceraldehyde-3-P?
1,3-bisphosphoglycerate
Which enzyme catalyzes the reaction that forms 1,3-bisphosphoglycerate from glyceraldehyde-3-P?
Glyceraldehyde-3-P dehydrogenase
What coenzyme is required for the oxidation step in the reaction forming 1,3-bisphosphoglycerate?
NAD⁺
What must be continually replenished in the cytosol to maintain flux through glycolysis?
NAD⁺
What are the four steps of the enzyme mechanism for glyceraldehyde-3-P dehydrogenase?
- Binding of glyceraldehyde-3-P to the enzyme
- Dehydrogenation of the aldehyde group
- Release of NADH and regeneration of NAD⁺
- Nucleophilic attack by phosphate ion
What is the standard free energy of hydrolysis for 1,3-bisphosphoglycerate?
−49.4 kJ/mol
What is the standard free energy of hydrolysis for ATP?
−30.5 kJ/mol
What accounts for the large favorable free energy change for phosphate hydrolysis of 1,3-bisphosphoglycerate?
Resonance stabilization of the product 3-phosphoglycerate
What is the biochemical standard free energy change for phosphoenolpyruvate?
−61.9 kJ/mol
What does the high phosphoryl transfer energy in 1,3-bisphosphoglycerate allow?
Phosphorylation of ADP to generate ATP
Which enzyme catalyzes the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate?
Phosphoglycerate kinase
How many ATP molecules are generated from one molecule of glucose during glycolysis?
2 ATP
What structural feature do phosphoglycerate kinase and hexokinase share?
They have two lobes, each binding a substrate molecule
What is the actual change in free energy for reactions 6 and 7?
Close to zero (ΔG ₌ −1.3 kJ/mol; ΔG ₌ −3.4 kJ/mol)
Which three enzymes in glycolysis catalyze irreversible reactions?
- Hexokinase
- Phosphofructokinase-1
- Pyruvate kinase
What is the side reaction involving 1,3-bisphosphoglycerate in erythrocytes?
Conversion to 2,3-bisphosphoglycerate (2,3-BPG)
What is the role of 2,3-bisphosphoglycerate in erythrocytes?
It is an allosteric regulator of hemoglobin
What does the presence of defects in glycolytic enzymes affect regarding oxygen transport?
Levels of 2,3-BPG
What is the purpose of reaction 8 in glycolysis?
To generate 2-phosphoglycerate
What enzyme catalyzes the reaction that forms 2-phosphoglycerate from 3-phosphoglycerate?
Phosphoglycerate mutase
What type of reaction does phosphoglycerate mutase catalyze?
Isomerization reaction
What is the mechanism of the phosphoglycerate mutase reaction based on?
Phosphoryl transfer from a phosphorylated histidine residue
What is the product formed from the dehydration of 2-phosphoglycerate?
Phosphoenolpyruvate
What enzyme catalyzes the dehydration of 2-phosphoglycerate to form phosphoenolpyruvate?
Enolase
What reaction does enolase catalyze in glycolysis?
The conversion of 2-phosphoglycerate to phosphoenolpyruvate through a dehydration reaction
This reaction increases the phosphoryl transfer potential of the triose sugar.
What is the standard free energy change (ΔG°′) for the conversion of 2-phosphoglycerate to phosphoenolpyruvate?
ΔG°′ = +1.7 kJ/mol
This indicates that the overall metabolic energy available from 2-phosphoglycerate or phosphoenolpyruvate is similar.
What is the significance of the enol form generated by enolase?
It traps the phosphoryl group in an unstable form, dramatically increasing the phosphoryl transfer potential
The biochemical standard free energy change for phosphate hydrolysis of 2-phosphoglycerate is ΔG°′ = -17.6 kJ/mol, while for phosphoenolpyruvate it is ΔG°′ = -61.9 kJ/mol.
What is substrate-level phosphorylation?
A mechanism for ATP production through the direct transfer of a phosphoryl group from a high-energy donor to ADP
This process is independent of ATP synthase.
Which enzymes catalyze the substrate-level phosphorylation reactions in glycolysis?
Phosphoglycerate kinase and pyruvate kinase
These enzymes transfer phosphoryl groups from substrates with high biochemical standard free energy changes.
How many ATP are generated from glycolysis per glucose molecule under anaerobic conditions?
Net yield of 2 ATP
This accounts for the 2 ATP invested in the initial stages of glycolysis.
What is the role of pyruvate kinase in glycolysis?
It catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP
This is the second substrate-level phosphorylation reaction in glycolysis.
What is the overall standard change in free energy (ΔG°′) for the glycolytic pathway?
The specific value is not provided in the text
The overall actual change in free energy (ΔG) for the glycolytic pathway also needs to be determined.
What is the key function of phosphoenolpyruvate in glycolysis?
It has a high phosphoryl transfer potential used to generate ATP
This potential is exploited in the reaction catalyzed by pyruvate kinase.
True or False: Pyruvate is a stable compound in cells.
True
Pyruvate is used by many other metabolic pathways.
Fill in the blank: The enzyme _______ catalyzes the conversion of glucose to glucose-6-phosphate.
hexokinase
Hexokinase is a key enzyme in glycolysis.
Fill in the blank: The enzyme _______ converts fructose-6-phosphate to fructose-1,6-bisphosphate.
phosphofructokinase-1
This enzyme is a key regulated enzyme in the glycolytic pathway.
