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What is glycolysis?
A metabolic pathway that breaks down one molecule of glucose into two molecules of pyruvate while generating ATP and NADH.
Where does glycolysis occur?
In the cytoplasm (cytosol) of the cell.
What is the primary purpose of glycolysis?
To break down glucose and capture some of its energy in the form of ATP and NADH.
How many molecules of pyruvate are produced from one molecule of glucose?
Two molecules of pyruvate.
How many ATP molecules are consumed during glycolysis?
Two ATP molecules.
How many ATP molecules are produced during glycolysis?
Four ATP molecules.
What is the net ATP yield of glycolysis?
Two ATP molecules per glucose molecule.
How many NADH molecules are produced during glycolysis?
Two NADH molecules per glucose molecule.
What are the two major stages of glycolysis?
Energy-investment stage.
Energy-payoff stage.
What happens during the energy-investment stage?
Glucose is trapped inside the cell, phosphorylated, and modified so that it can be cleaved into two phosphorylated three-carbon compounds.
What happens during the energy-payoff stage?
The three-carbon compounds are oxidized to pyruvate, producing ATP and NADH.
Why must glucose be phosphorylated during the beginning of glycolysis?
Phosphorylation traps glucose inside the cell because glucose 6-phosphate cannot readily cross the plasma membrane.
What enzyme catalyzes the first reaction of glycolysis?
Hexokinase.
What reaction does hexokinase catalyze?
Glucose + ATP → glucose 6-phosphate + ADP.
What is the purpose of the hexokinase reaction?
To phosphorylate glucose and trap it inside the cell.
What inhibits hexokinase?
Glucose 6-phosphate through feedback inhibition.
What enzyme converts glucose 6-phosphate into fructose 6-phosphate?
Phosphoglucose isomerase.
What type of reaction does phosphoglucose isomerase catalyze?
An isomerization reaction that converts an aldose into a ketose.
What enzyme catalyzes the third reaction of glycolysis?
Phosphofructokinase-1 (PFK-1).
What reaction does phosphofructokinase-1 catalyze?
Fructose 6-phosphate + ATP → fructose 1,6-bisphosphate + ADP.
Why is phosphofructokinase-1 especially important?
It catalyzes a major irreversible, rate-controlling step of glycolysis and is a key regulator of the pathway.
What enzyme splits fructose 1,6-bisphosphate into two three-carbon molecules?
Aldolase.
What two products are formed by aldolase?
Glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP).
What enzyme converts DHAP into GAP?
Triose phosphate isomerase.
Why must DHAP be converted into GAP?
GAP is the three-carbon molecule that continues through the payoff phase of glycolysis.
How many GAP molecules proceed through the payoff phase for each glucose molecule?
Two GAP molecules.
What enzyme catalyzes the oxidation of GAP?
Glyceraldehyde 3-phosphate dehydrogenase (GAPDH).
What reaction does glyceraldehyde 3-phosphate dehydrogenase catalyze?
GAP is oxidized and inorganic phosphate is incorporated to form 1,3-bisphosphoglycerate.
What coenzyme is reduced during the GAPDH reaction?
NAD+ is reduced to NADH.
What is the importance of the GAPDH reaction?
It captures energy from oxidation in the high-energy compound 1,3-bisphosphoglycerate while generating NADH.
What enzyme converts 1,3-bisphosphoglycerate into 3-phosphoglycerate?
Phosphoglycerate kinase.
What happens during the phosphoglycerate kinase reaction?
A phosphate group is transferred from 1,3-bisphosphoglycerate to ADP, producing ATP and 3-phosphoglycerate.
What type of ATP production occurs during the phosphoglycerate kinase reaction?
Substrate-level phosphorylation.
Why is 1,3-bisphosphoglycerate capable of generating ATP?
It has a higher phosphoryl-transfer potential than ATP.
What enzyme converts 3-phosphoglycerate into 2-phosphoglycerate?
Phosphoglycerate mutase.
What enzyme converts 2-phosphoglycerate into phosphoenolpyruvate (PEP)?
Enolase.
What type of reaction does enolase catalyze?
A dehydration reaction that removes water and forms PEP.
Why is PEP considered a high-energy compound?
Its phosphate group has a high transfer potential because the phosphate traps the compound in an unstable enol tautomer.
What enzyme catalyzes the final reaction of glycolysis?
Pyruvate kinase.
What reaction does pyruvate kinase catalyze?
PEP transfers its phosphate to ADP, producing ATP and pyruvate.
What type of ATP production occurs during the pyruvate kinase reaction?
Substrate-level phosphorylation.
What are the three irreversible reactions of glycolysis?
Glucose → glucose 6-phosphate (hexokinase).
Fructose 6-phosphate → fructose 1,6-bisphosphate (phosphofructokinase-1).
PEP → pyruvate (pyruvate kinase).
Why are irreversible reactions important in metabolic regulation?
They are potential control points because their reactions cannot simply reverse under normal physiological conditions.
What is NAD+?
An oxidized coenzyme that accepts electrons during metabolic reactions.
What is NADH?
The reduced form of NAD+ that carries high-energy electrons.
What happens to NAD+ during glycolysis?
It accepts electrons during the oxidation of GAP and becomes NADH.
Why must NADH be converted back into NAD+?
Glycolysis requires NAD+ to continue oxidizing GAP and producing ATP.
What is fermentation?
A metabolic process that regenerates NAD+ by transferring electrons from NADH to an organic molecule.
What are the two fermentation pathways discussed in the chapter?
Lactic acid fermentation and alcoholic fermentation.
What happens during lactic acid fermentation?
Pyruvate is reduced to lactate by lactate dehydrogenase, regenerating NAD+ from NADH.
What enzyme catalyzes the conversion of pyruvate into lactate?
Lactate dehydrogenase.
What happens to NADH during lactic acid fermentation?
NADH is oxidized back into NAD+.
What happens during alcoholic fermentation?
Pyruvate is converted into ethanol and carbon dioxide, regenerating NAD+.
What organism commonly uses alcoholic fermentation?
Yeast.
What is the primary purpose of fermentation?
To regenerate NAD+ so glycolysis can continue producing ATP.
Does fermentation itself produce additional ATP?
No. Its main function is NAD+ regeneration. ATP is generated through glycolysis
Why is NAD+ regeneration essential under anaerobic conditions?
Without oxygen-dependent respiration to reoxidize NADH, fermentation must regenerate NAD+ to sustain glycolysis.
Where does fructose come from in the diet?
Table sugar (sucrose) and high-fructose corn syrup.
Where does galactose come from in the diet?
Milk sugar (lactose).
What happens to fructose and galactose during metabolism?
They are converted into intermediates that can enter glycolysis.
Why can fructose and galactose be used for energy production?
Their metabolic pathways convert them into compounds that enter glycolysis.
Which three enzymes catalyze the irreversible reactions of glycolysis and serve as major control points?
Hexokinase.
Phosphofructokinase-1.
Pyruvate kinase.
What is allosteric regulation?
Regulation of an enzyme by the binding of a molecule at a site other than the active site, causing a change in enzyme activity.
What is feedback inhibition?
A regulatory process in which a product or downstream signal inhibits an earlier enzyme in a pathway.
What is the primary allosteric regulator of glycolysis in mammals?
Phosphofructokinase-1.
How does ATP affect phosphofructokinase-1?
ATP allosterically inhibits PFK-1, signaling that cellular energy is sufficient.
How does AMP affect phosphofructokinase-1?
AMP allosterically stimulates PFK-1, signaling a low-energy state.
Why does AMP increase when ATP demand is high?
Adenylate kinase converts two ADP molecules into ATP and AMP.
What reaction does adenylate kinase catalyze?
2 ADP ⇌ ATP + AMP.
What happens to glycolysis when ATP levels are high?
Glycolysis is inhibited because the cell has sufficient energy.
What happens to glycolysis when AMP levels are high?
Glycolysis is stimulated to increase ATP production.
What inhibits hexokinase in muscle?
Glucose 6-phosphate.
What inhibits pyruvate kinase in muscle?
ATP and alanine.
What stimulates pyruvate kinase in muscle?
Fructose 1,6-bisphosphate through feed-forward activation.
Why is pyruvate kinase stimulated by fructose 1,6-bisphosphate?
It coordinates the activity of later glycolytic reactions with the activity of earlier reactions, helping maintain pathway flow.
What are the key regulators of phosphofructokinase in the liver?
Citrate and fructose 2,6-bisphosphate
How does citrate affect phosphofructokinase?
Citrate inhibits phosphofructokinase, signaling that the citric acid cycle has sufficient intermediates or energy.
How does fructose 2,6-bisphosphate affect phosphofructokinase-1?
It is a powerful activator of PFK-1.
What is the function of fructose 2,6-bisphosphate in regulating glucose metabolism?
It stimulates glycolysis and inhibits gluconeogenesis.
What is the role of glycolysis in pancreatic beta cells?
Glycolysis contributes to glucose metabolism and energy production, helping pancreatic beta cells sense glucose availability and regulate insulin secretion.
What is the role of NAD⁺ in glycolysis?
NAD⁺ acts as an electron acceptor. During the glyceraldehyde-3-phosphate dehydrogenase reaction, NAD⁺ accepts electrons and hydrogen from glyceraldehyde-3-phosphate and becomes NADH.
What is the role of NADH in glycolysis?
NADH carries the high-energy electrons collected during glycolysis. These electrons can be transferred to the electron transport chain when oxygen is available. When oxygen is limited, NADH can be used to reduce pyruvate to lactate, regenerating NAD⁺.
Which glycolysis enzyme requires NAD⁺?
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
What happens if NAD⁺ is not regenerated during glycolysis?
The GAPDH reaction cannot continue, so glycolysis stops and the cell loses an important source of ATP.
How does insulin affect glucose metabolism in muscle?
Insulin stimulates glucose uptake into skeletal muscle by promoting the movement of GLUT4 transporters to the cell membrane. This increases glucose availability for glycolysis and glycogen synthesis.
How does epinephrine affect glucose metabolism in muscle?
Epinephrine stimulates glycogen breakdown (glycogenolysis), increasing the availability of glucose-6-phosphate for glycolysis and ATP production during muscle activity.
What is the difference between insulin and epinephrine in muscle?
Insulin generally promotes glucose uptake and storage as glycogen. Epinephrine promotes glycogen breakdown to provide fuel for energy production.
What are the three major irreversible steps of glycolysis?
Glucose → glucose-6-phosphate: hexokinase (or glucokinase in liver).
Fructose-6-phosphate → fructose-1,6-bisphosphate: phosphofructokinase-1 (PFK-1).
Phosphoenolpyruvate → pyruvate: pyruvate kinase.
Which enzyme is the major regulatory enzyme of glycolysis?
Phosphofructokinase-1 (PFK-1). It catalyzes the committed, highly regulated step of glycolysis.
How does ATP regulate glycolysis?
High ATP levels inhibit PFK-1, slowing glycolysis because the cell has sufficient energy. Low ATP and high AMP stimulate PFK-1, increasing glycolysis.
How does fructose-2,6-bisphosphate affect glycolysis?
Fructose-2,6-bisphosphate activates PFK-1, stimulating glycolysis.
How does citrate affect glycolysis?
High citrate inhibits PFK-1, signaling that the cell has sufficient energy and metabolic intermediates.
Why can't gluconeogenesis simply reverse glycolysis?
Three reactions in glycolysis are essentially irreversible and must be bypassed using different enzymes.
What happens when cellular energy levels are low?
AMP increases, stimulating glycolysis to generate ATP.
What happens when cellular energy levels are high?
ATP inhibits phosphofructokinase-1, reducing glycolytic activity.
What happens when fructose-2,6-bisphosphate levels increase?
Glycolysis increases and gluconeogenesis decreases.
Which enzymes convert glucose into fructose-1,6-bisphosphate?
Hexokinase: Glucose → G6P
Phosphoglucose isomerase: G6P → F6P
PFK-1: F6P → F1,6BP
What does aldolase do?
Splits fructose-1,6-bisphosphate into DHAP and GAP.
What does triose phosphate isomerase do?
Converts DHAP → GAP.
What does GAPDH do?
Oxidizes GAP and produces NADH.