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Questions and Answers
What is the net yield of ATP produced per mole of glucose during glycolysis?
What is the net yield of ATP produced per mole of glucose during glycolysis?
What regulates the activity of phosphofructokinase-1 (PFK-1) in skeletal muscle?
What regulates the activity of phosphofructokinase-1 (PFK-1) in skeletal muscle?
How many moles of NADH are produced per mole of glucose in glycolysis?
How many moles of NADH are produced per mole of glucose in glycolysis?
What role does ATP play in the regulation of phosphofructokinase-1?
What role does ATP play in the regulation of phosphofructokinase-1?
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Which of the following statements correctly describes the changes in free energy during glycolysis?
Which of the following statements correctly describes the changes in free energy during glycolysis?
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What role do the three large negative standard free-energy changes play in glycolysis?
What role do the three large negative standard free-energy changes play in glycolysis?
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Which enzyme is primarily responsible for the conversion of pyruvate to acetyl-CoA?
Which enzyme is primarily responsible for the conversion of pyruvate to acetyl-CoA?
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In which tissue is pyruvate kinase regulation specific to the liver isoenzyme observed?
In which tissue is pyruvate kinase regulation specific to the liver isoenzyme observed?
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In the equation G = H - TS, which terms contribute to the determination of free energy?
In the equation G = H - TS, which terms contribute to the determination of free energy?
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What is the significance of the free energy change (∆G) being negative in a reaction?
What is the significance of the free energy change (∆G) being negative in a reaction?
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How many allosteric regulatory sites does phosphofructokinase-1 (PFK-1) possess?
How many allosteric regulatory sites does phosphofructokinase-1 (PFK-1) possess?
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Which of the following is an allosteric activator of phosphofructokinase-1?
Which of the following is an allosteric activator of phosphofructokinase-1?
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What molecule is produced alongside pyruvate in the glycolytic pathway?
What molecule is produced alongside pyruvate in the glycolytic pathway?
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What does the term 'exergonic' imply about a biochemical reaction?
What does the term 'exergonic' imply about a biochemical reaction?
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Which of the following statements about the regulatory mechanisms of PFK-1 is true?
Which of the following statements about the regulatory mechanisms of PFK-1 is true?
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What is the effect of AMP on phosphofructokinase-1 under physiologic conditions?
What is the effect of AMP on phosphofructokinase-1 under physiologic conditions?
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What is the primary role of phosphofructokinase-1 (PFK-1) in glycolysis?
What is the primary role of phosphofructokinase-1 (PFK-1) in glycolysis?
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Which of the following statements about PFK-1 is true?
Which of the following statements about PFK-1 is true?
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What initiates the reaction catalyzed by PFK-1?
What initiates the reaction catalyzed by PFK-1?
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Which type of enzymatic reaction does PFK-1 perform?
Which type of enzymatic reaction does PFK-1 perform?
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How does PFK-1 contribute to the glycolytic pathway?
How does PFK-1 contribute to the glycolytic pathway?
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What does tissue-specific isoenzymes of PFK-1 indicate?
What does tissue-specific isoenzymes of PFK-1 indicate?
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What is the significance of the thermodynamic irreversibility of PFK-1's reaction?
What is the significance of the thermodynamic irreversibility of PFK-1's reaction?
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Which two reactants are transformed during the reaction catalyzed by PFK-1?
Which two reactants are transformed during the reaction catalyzed by PFK-1?
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What is the Km characteristic of glucokinase compared to other hexokinases?
What is the Km characteristic of glucokinase compared to other hexokinases?
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In which tissues is glucokinase primarily found?
In which tissues is glucokinase primarily found?
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What is the significance of the binding of hexokinase to porins in the outer mitochondrial membrane?
What is the significance of the binding of hexokinase to porins in the outer mitochondrial membrane?
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What is formed when glucose 6-P is isomerized?
What is formed when glucose 6-P is isomerized?
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Why is the isomerization of glucose 6-P essential?
Why is the isomerization of glucose 6-P essential?
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What effect does a lower Km value have on an enzyme's binding to its substrate?
What effect does a lower Km value have on an enzyme's binding to its substrate?
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What happens to glucose 6-P after it is isomerized to fructose 6-phosphate?
What happens to glucose 6-P after it is isomerized to fructose 6-phosphate?
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Which enzyme is known to take glucose only at lower speeds?
Which enzyme is known to take glucose only at lower speeds?
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What is the primary product of anaerobic conversion of pyruvate in yeast?
What is the primary product of anaerobic conversion of pyruvate in yeast?
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Which enzyme is responsible for decarboxylating pyruvate?
Which enzyme is responsible for decarboxylating pyruvate?
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Which coenzyme is tightly bound to pyruvate decarboxylase?
Which coenzyme is tightly bound to pyruvate decarboxylase?
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Why do lens cells not need oxygen or capillaries?
Why do lens cells not need oxygen or capillaries?
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What is the role of NADH in the conversion of pyruvate to ethanol?
What is the role of NADH in the conversion of pyruvate to ethanol?
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What is the significance of ethanol synthesis by yeast?
What is the significance of ethanol synthesis by yeast?
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What type of reaction is catalyzed by alcohol dehydrogenase?
What type of reaction is catalyzed by alcohol dehydrogenase?
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Which ion is required for the activity of pyruvate decarboxylase?
Which ion is required for the activity of pyruvate decarboxylase?
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What effect does high ATP concentration have on PFK-1 activity?
What effect does high ATP concentration have on PFK-1 activity?
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Which factor primarily regulates glycolysis in the short term?
Which factor primarily regulates glycolysis in the short term?
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What is the result of regular consumption of carbohydrate-rich meals on specific liver enzymes?
What is the result of regular consumption of carbohydrate-rich meals on specific liver enzymes?
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How does the binding of AMP affect PFK-1 isoenzymes?
How does the binding of AMP affect PFK-1 isoenzymes?
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Which of the following is an effect of hormonal regulation on glycolysis?
Which of the following is an effect of hormonal regulation on glycolysis?
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What is the typical response of PFK-1 activity versus fructose-6-phosphate concentration at high ATP levels?
What is the typical response of PFK-1 activity versus fructose-6-phosphate concentration at high ATP levels?
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What major products are indicated in the pathways for blood glucose production?
What major products are indicated in the pathways for blood glucose production?
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What process most affects the long-term regulation of enzyme protein synthesis in glycolysis?
What process most affects the long-term regulation of enzyme protein synthesis in glycolysis?
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Study Notes
Glycolysis
- Glycolysis is the breakdown of glucose to pyruvate in the cytoplasm
- It occurs in 10 steps and generates ATP and NADH.
- The process generates 2 ATP and 2 NADH.
- Key enzymes include hexokinase, phosphofructokinase-1, pyruvate kinase.
- The steps are regulated to ensure that glucose metabolism is efficient and controlled.
Metabolic fates of pyruvate
- Pyruvate can be converted to lactate, acetyl CoA, or other compounds under different conditions.
- Aerobic conditions: Pyruvate is converted to acetyl CoA, which enters the citric acid cycle for further oxidation.
- Anaerobic conditions: Pyruvate is reduced to lactate, regenerating NAD+ to continue glycolysis.
- The fate of pyruvate depends on the presence of oxygen and the cell's needs.
State of reduction of carbon atoms in biomolecules
- Fats, carbohydrates, carbonyls, and carboxyls are decreased in state of reduction with carbon dioxide.
- In living organisms, energy used for biosynthetic reactions is derived from the oxidation of organic substrates.
- In aerobic organisms, oxygen is the ultimate electron acceptor, which is reduced as a byproduct of the process.
- An example is the oxidation of glucose in the presence of oxygen as shown in the image.
Energy levels of electrons
- Energy is the capacity to cause change.
- Electrons have potential energy due to their distance from the atomic nucleus.
- Changes in potential energy occur in fixed amounts.
- Electron energy level is correlated with its average distance from the nucleus.
- The ball-bouncing-down-the-stairs analogy is used to visually explain.
Stepwise energy harvest via NAD+
- In cellular respiration, organic compounds are broken down in steps, with electrons being transferred to NAD+ first.
- NAD+ is reduced to NADH, which carries electrons.
- NAD+ is a coenzyme involved in electron transport (oxidizes NADH).
- The chemical structure of oxidized and reduced forms of NAD+ is given.
Overview of carbohydrate digestion
- Starches, lactose, and sucrose are the major carbohydrates in the diet.
- Starches are polysaccharides composed of glucose units linked together through a-1,4- and α-1,6 -glycosidic bonds.
- Lactose is a disaccharide made of glucose and galactose.
- Sucrose is a disaccharide made of glucose and fructose.
- Digestion breaks down these molecules into their constituent monosaccharides (glucose, galactose, fructose) for energy production.
Overview of carbohydrate metabolism
- Glucose is important to cells because it is a universal fuel and energy source.
- After being transported into cells, glucose is phosphorylated to glucose-6-phosphate.
- The three common pathways are glycolysis, pentose phosphate pathway, and glycogen synthesis.
- Fructose and galactose are converted into intermediates of glucose metabolism.
Overview of glycolysis and the TCA cycle
- Glycolysis begins with the phosphorylation of glucose to glucose 6-phosphate.
- Glycolysis occurs in the cytosol.
- NADH cannot cross the mitochondrial membrane; its reducing equivalents are transferred using shuttles.
- Pyruvate is oxidized to CO2 using pyruvate dehydrogenase and TCA cycle.
Energy Investment Phase
- The beginning phase of glycolysis that utilizes ATP to phosphorylate glucose.
- Phosphorylation of glucose commits glucose to metabolism in the cell and prevents the glucose from leaving the cell.
- The process involves multiple enzyme-catalyzed reactions.
Isomerization of glucose 6-phosphate to fructose 6-phosphate
- Converting glucose 6-phosphate to fructose 6-phosphate is necessary for further reactions in glycolysis.
- This is catalyzed by an enzyme called phosphoglucose isomerase.
- The process involves an isomerization, going from an aldehyde to a ketone.
Reaction of the PFK-1 within the Energy Investment Phase
- Phosphofructokinase-1 (PFK-1) is the first committed step in glycolysis.
- Phosphorylation of fructose 6-phosphate produces fructose 1,6-bisphosphate.
Aldol cleavage within the Energy Investment Phase
- Fructose 1,6-bisphosphate is cleaved into two three-carbon compounds through the aldolase, producing Dihydroxyacetone phosphate (DHAP) and Glyceraldehyde-3-phosphate.
Mechanism for the fructose-1,6-bisphosphate aldolase reaction
- Aldolase activates the substrate by cleaving.
- Reaction involves nucleophilic attack catalyzed by an active site lysine ε-amino group and an aspartate residue.
- Formation of a covalent intermediate, Schiff base, that is crucial for the reaction.
Energy Payoff Phase
- The energy payoff phase of glycolysis yields ATP through substrate-level phosphorylation, utilizing high-energy phosphate bonds in the metabolic intermediates.
Reactions of the Glyceraldehyde 3-P dehydrogenase
- Glyceraldehyde-3-P is oxidized and phosphorylated to 1,3-bisphosphoglycerate generating NADH.
- This high-energy intermediate is later used in substrate-level phosphorylation to produce ATP.
Reactions in steps 8-10 of the Energy Payoff Phase
- Converting 3-phosphoglycerate to pyruvate through a series of reactions leading to PEP and then to pyruvate.
- This phase generates ATP.
Phases of the glycolytic pathway
- Glycolysis is divided into an energy investment phase and an energy payoff phase.
- Glycolysis involves a net gain of 2 ATP using 2 ATP.
- Glycolysis creates 2 pyruvates, 2NADH, and 2H+.
The critical reaction steps in glycolysis
- Glycolysis has 3 irreversible reactions: hexokinase, phosphofructokinase-1, pyruvate kinase,
- These steps are crucial because they are regulated.
- The free energy change in these reactions is large and negative.
Major sites of regulation in the glycolytic pathway
- Hexokinase and phosphofructokinase-1 are major regulatory enzymes in skeletal muscle, impacting pyruvate metabolism.
- The activity of pyruvate dehydrogenase impacts whether pyruvate is converted to lactate or acetyl coenzyme A.
- Regulation of pyruvate kinase occurs only in the liver.
Regulation of Phosphofructokinase-1
- PFK-1 is an allosteric enzyme, meaning it has different binding sites for substrates and regulatory molecules.
- ATP is an inhibitor; AMP is an activator, influencing the enzyme's affinity for fructose-6-phosphate.
Regulation of Glucose content
- Pathways for glucose metabolism and regulation are complex, involving multiple substrates and enzymes.
Hormonal regulation of glycolysis
- Short-term control of glycolysis involves allosteric regulation and phosphorylation/dephosphorylation of enzymes.
- Longer-term control involves hormonal influences (insulin, glucagon) and changes in enzymes synthesized.
- For example, elevated carbohydrate intake or insulin administration promotes glucokinase, phosphofructokinase, pyruvate kinase.
Biosynthetic functions of glycolysis
- Glycolysis produces precursors for other metabolic pathways, including the synthesis of nucleotides, fatty acids, and glycerol-3-phosphate.
Anaerobic glycolysis
- Without oxygen, pyruvate is converted to lactate via lactate dehydrogenase, regenerating NAD+.
- This allows glycolysis to continue producing ATP, but at a lower rate compared to aerobic reactions.
- The buildup of lactic acid can lead to an increase in acidity in the cells.
Oxidative fates of pyruvate and NAD+
- Aerobic glycolysis: Pyruvate is converted to acetyl CoA, which enters the TCA cycle.
- Anaerobic glycolysis: Pyruvate to lactate, regenerating NAD+.
- NADH from glycolysis can be reoxidized in different ways depending on the availability of oxygen and the cell type.
Lactate dehydrogenase reaction
- Lactate dehydrogenase is an enzyme that catalyzes the interconversion of pyruvate and lactate, while regenerating NAD+.
- The equilibrium of this reaction favors lactate formation, which is crucial for anaerobic conditions.
Fermented milk products
- Yogurt and Dahi are produced through bacterial fermentation of milk catalyzed by Lactobacillus and Streptococcus.
- The bacteria convert lactose to lactic acid, impacting the texture and flavor.
Fate of Lactate (Cori Cycle)
- Lactate can be shuttled from tissues to liver where gluconeogenesis occurs to convert lactate to glucose.
- The lactate produced during anaerobic glycolysis can be used by other tissues or converted back to glucose in the liver.
Tissues of the eye and anaerobic glycolysis
- The eye requires anaerobic glycolysis for energy production in structures like the lens, as the cells involved lack mitochondria.
Anaerobic conversion of pyruvate to ethanol
- Yeast converts pyruvate into ethanol and CO2.
- This process regenerates NAD+ to keep glycolysis going under anaerobic conditions.
- This is part of fermentation.
TPP and its role in pyruvate decarboxylation
- Thiamine pyrophosphate (TPP) is a coenzyme needed for pyruvate decarboxylation.
- It is involved in a crucial transition state that stabilizes the process of decarboxylation.
Production of Swiss Cheese
- Swiss cheese production involves several bacteria, including propionibacteria, consuming lactic acid and producing gases that create holes.
- Flavor compounds are produced during fermentation.
Fermentation Overview
- Fermentation is an anaerobic metabolic process where pyruvate is produced and oxidized, creating products like lactate and ethanol.
Major pathways for fermentation of sugars
- Various microorganisms and organisms use fermentation to convert sugars to different end products depending on specific organisms.
Industrial products from fermentations
- Various microorganisms are involved in producing different foods and chemicals using fermentation.
The evolutionary significance of Glycolysis
- Glycolysis is a fundamental metabolic pathway found in most organisms.
- The cytosol location of glycolysis points to its ancient origin.
- The reactions are regulated by certain conditions.
Comparison of fermentation and respiration
- Fermentations occur in the absence of oxygen.
- Respiration requires oxygen and occurs in mitochondria. Glycolysis is the first stage of both.
Quiz Questions and Answers
- The questions cover various aspects of glycolysis, its regulation, and its relationship with other metabolic pathways.
- The answers are provided, and direct answers are given without unnecessary re-explanations.
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