Biochemistry: Glucose Metabolism Lecture

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Questions and Answers

What type of phosphorylation occurs during the conversion of 1,3-Bisphosphoglycerate to 3-Phosphoglycerate?

  • Oxidative phosphorylation
  • Substrate level phosphorylation (correct)
  • Oxidative decarboxylation
  • Photophosphorylation

How many molecules of ATP are produced in the reaction catalyzed by ATP kinase when converting Phosphoenolpyruvate to Pyruvate?

  • Three molecules
  • Two molecules (correct)
  • Four molecules
  • One molecule

Which molecule is formed as a product of the reaction catalyzed by enolase?

  • 1,3-Bisphosphoglycerate
  • 2-Phosphoglycerate
  • Pyruvate
  • Phosphoenolpyruvate (correct)

What is the main role of the enzyme mutase in glycolysis?

<p>Move phosphate groups (C)</p> Signup and view all the answers

Why is the reaction converting 3-Phosphoglycerate to 2-Phosphoglycerate considered unremarkable?

<p>It merely involves the movement of a phosphate group (D)</p> Signup and view all the answers

In the glycolytic pathway, at which stage is NADH produced?

<p>During the conversion of Glyceraldehyde-3-phosphate (B)</p> Signup and view all the answers

Which compound serves as a key intermediate before ATP synthesis occurs from 1,3-Bisphosphoglycerate?

<p>3-Phosphoglycerate (A)</p> Signup and view all the answers

What is primarily happening when the enzyme ATP kinase functions in glycolysis?

<p>Transfer of phosphate from a substrate to ADP (D)</p> Signup and view all the answers

What is the net yield of ATP from glycolysis after considering the early and later stages?

<p>2 ATP (D)</p> Signup and view all the answers

Which cofactor is regenerated during the conversion of pyruvate to lactate?

<p>NAD+ (C)</p> Signup and view all the answers

How does the body respond to limited oxygen supplies regarding pyruvate metabolism?

<p>Pyruvate is converted to lactate (D)</p> Signup and view all the answers

Which of the following is NOT a metabolic fate of pyruvate when oxygen is present?

<p>Conversion to lactate (A)</p> Signup and view all the answers

What type of control primarily regulates the pathway of glycolysis?

<p>Allosteric and hormonal control (A)</p> Signup and view all the answers

Which molecule serves as the allosteric inhibitor for phosphofructokinase?

<p>ATP (D)</p> Signup and view all the answers

In the case of excess caloric intake, pyruvate is primarily converted into which of the following?

<p>Fatty acids (D)</p> Signup and view all the answers

What is the primary role of lactate dehydrogenase in the context of pyruvate metabolism?

<p>Catalyzes the conversion of pyruvate to lactate (D)</p> Signup and view all the answers

What is the primary energy yield from glycolysis?

<p>2 ATP (B)</p> Signup and view all the answers

Which cell type relies solely on glycolysis for ATP production due to lack of mitochondria?

<p>Red blood cells (B)</p> Signup and view all the answers

What is produced at a high rate by tumour cells through anaerobic glycolysis?

<p>Lactate (A)</p> Signup and view all the answers

Which pathway allows for ATP production under both aerobic and anaerobic conditions?

<p>Glycolysis (A)</p> Signup and view all the answers

Which of the following substances is a main intermediate produced during glycolysis and can enter the mitochondria for further ATP production?

<p>Acetyl CoA (C)</p> Signup and view all the answers

Which tissues are specifically noted for their high reliance on glycolysis?

<p>Brain, skeletal muscle, and red blood cells (A)</p> Signup and view all the answers

What effect does ATP have on phosphofructokinase during glycolysis?

<p>It inhibits the enzyme (A)</p> Signup and view all the answers

What is the Warburg effect commonly associated with in terms of cellular metabolism?

<p>Preferential anaerobic glycolysis in tumor cells (A)</p> Signup and view all the answers

What is the primary function of the liver in relation to glucose compared to the brain when blood glucose levels are low?

<p>Store excess glucose efficiently (A)</p> Signup and view all the answers

In which reaction does fructose 6-phosphate convert to fructose 1,6-bisphosphate?

<p>Phosphofructo-kinase (C)</p> Signup and view all the answers

What is the result of the reaction involving aldolase?

<p>Conversion of a 6-carbon sugar into two 3-carbon units (D)</p> Signup and view all the answers

What is the significance of the reaction involving glyceraldehyde 3-phosphate dehydrogenase?

<p>It generates NADH, which is used later in oxidative phosphorylation (D)</p> Signup and view all the answers

Which substance is produced when glyceraldehyde 3-phosphate undergoes oxidation?

<p>NADH (D)</p> Signup and view all the answers

What explains the higher Km and higher Vmax of the liver's glucose utilization compared to that of muscles?

<p>The liver must store excess glucose when levels are high (D)</p> Signup and view all the answers

How many times will all reactions occur from glucose to produce ATP through glycolysis?

<p>Twice, because two 3-carbon units are produced (C)</p> Signup and view all the answers

Which reaction serves as a key regulatory step in glycolysis?

<p>Conversion of fructose 6-phosphate to fructose 1,6-bisphosphate (B)</p> Signup and view all the answers

What is the correct net yield of ATP from anaerobic glycolysis?

<p>2 ATP per glucose molecule (B)</p> Signup and view all the answers

During anaerobic glycolysis, how many ATP molecules are consumed in the initial steps?

<p>2 ATP are consumed (A)</p> Signup and view all the answers

In anaerobic glycolysis, which compound is primarily produced from glucose?

<p>Lactate (B)</p> Signup and view all the answers

What role does NAD+ play during anaerobic glycolysis?

<p>It is reduced to NADH (D)</p> Signup and view all the answers

In anaerobic conditions, what happens to the pyruvate produced during glycolysis?

<p>It is fermented to lactate (D)</p> Signup and view all the answers

Which enzyme is responsible for converting glucose to glucose 6-phosphate in glycolysis?

<p>Hexokinase (C)</p> Signup and view all the answers

What is the terminal product of anaerobic glycolysis?

<p>Lactate (C)</p> Signup and view all the answers

How many total ATP molecules can be generated from one molecule of glucose during glycolysis, considering both invested and produced ATP?

<p>4 ATP molecules (C)</p> Signup and view all the answers

Which intermediate is formed after the conversion of fructose 1,6-bisphosphate in glycolysis?

<p>Dihydroxyacetone phosphate and glyceraldehyde 3-phosphate (D)</p> Signup and view all the answers

What is the primary function of glycolysis in cellular metabolism?

<p>ATP synthesis and energy capture (B)</p> Signup and view all the answers

Which of the following enzymes is responsible for the phosphorylation of glucose in the glycolysis pathway?

<p>Hexokinase (A)</p> Signup and view all the answers

What type of molecule is glucose classified as?

<p>Monosaccharide (A)</p> Signup and view all the answers

What are the end products of glycolysis from one molecule of glucose?

<p>2 ATP and 2 pyruvate (A)</p> Signup and view all the answers

Which of the following is NOT a source of glucose for glycolysis?

<p>Direct conversion of fatty acids (A)</p> Signup and view all the answers

What is the role of lactate dehydrogenase in anaerobic conditions?

<p>To regenerate NAD+ from NADH (D)</p> Signup and view all the answers

Which of the following statements about ATP synthesis in glycolysis is true?

<p>ATP is produced by substrate-level phosphorylation (A)</p> Signup and view all the answers

In which part of the cell does glycolysis take place?

<p>Cytosol (D)</p> Signup and view all the answers

Which enzyme in glycolysis is specifically inhibited by glucose-6-phosphate?

<p>Hexokinase (C)</p> Signup and view all the answers

Which metabolic event occurs during the oxidation phase of glycolysis?

<p>Removal of hydrogen atoms (D)</p> Signup and view all the answers

What is the significance of the high Km of glucokinase?

<p>It allows the liver to respond to high glucose levels (A)</p> Signup and view all the answers

Which statement correctly describes the role of glycolysis in red blood cells?

<p>Glycolysis is the only source of ATP (B)</p> Signup and view all the answers

Why is it important to regenerate NAD+ in the glycolysis pathway?

<p>It allows glycolysis to continue running (D)</p> Signup and view all the answers

Flashcards

Glucose

A monosaccharide (simple sugar) that is the primary energy source for most cells.

Glycogen

A polysaccharide (complex sugar) that acts as a medium-term energy store in the body. It is primarily composed of glucose units linked together.

Glycolysis

The metabolic pathway that breaks down glucose into pyruvate. It occurs in the cytosol of all cells and involves a series of 10 enzymatic reactions.

Substrate-level phosphorylation

The process of generating ATP from ADP using the energy released from breaking down high-energy phosphate molecules within the glycolysis pathway.

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Hexokinase

An enzyme that catalyzes the reversible interconversion of glucose and glucose 6-phosphate. Found in all tissues.

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Glucokinase

An enzyme that catalyzes the conversion of glucose to glucose 6-phosphate. Found primarily in the liver.

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Activation stage of glycolysis

The stage of glycolysis that involves the addition of phosphate groups, requiring the use of ATP.

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Phosphofructokinase

The key regulatory enzyme in the glycolysis pathway. It catalyzes the conversion of fructose 6-phosphate to fructose 1,6-bisphosphate, a committed step in glycolysis.

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Pyruvate

A product of glycolysis, a three-carbon molecule that can be further processed in the citric acid cycle or under anaerobic conditions.

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Anaerobic metabolism (fermentation)

A process that regenerates NAD+ from NADH under anaerobic conditions, allowing glycolysis to continue even in the absence of oxygen. It converts pyruvate to lactate.

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Lactate dehydrogenase

An enzyme that catalyzes the conversion of pyruvate to lactate, a key step in anaerobic metabolism.

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Glycolysis in red blood cells

The process used by red blood cells to generate energy as they lack mitochondria for aerobic respiration.

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Glycogenesis

The process by which glucose is converted into glycogen, providing a storage form for energy in the liver and muscles.

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Glycogenolysis

The process by which glycogen is broken down into glucose, releasing stored energy.

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Liver and Muscle Glucose Isoforms

The liver and muscle have different isoforms of the enzyme, resulting in different affinities for glucose. The liver's higher Km means it requires higher glucose concentrations for optimal activity, allowing it to store excess glucose.

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What does Phosphohexose Isomerase do?

Phosphohexose isomerase converts glucose 6-phosphate to fructose 6-phosphate, changing the sugar from an aldose to a ketose.

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What does Phosphofructokinase do?

Phosphofructokinase (PFK) catalyzes the phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate, using ATP as an energy source.

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Why is Phosphofructokinase important?

Phosphofructokinase (PFK) is a key regulatory enzyme in glycolysis, controlling the rate of sugar breakdown. It's a crucial step for controlling energy production.

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What does Aldolase do?

Aldolase splits fructose 1,6-bisphosphate into two 3-carbon units: glyceraldehyde 3-phosphate and dihydroxyacetone phosphate.

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What does Triose Phosphate Isomerase do?

Dihydroxyacetone phosphate is converted to glyceraldehyde 3-phosphate, ensuring that all glucose-derived carbon eventually becomes glyceraldehyde 3-phosphate for further processing in glycolysis.

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What does Glyceraldehyde 3-Phosphate Dehydrogenase do?

Glyceraldehyde 3-phosphate dehydrogenase converts glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate, producing NADH and releasing an inorganic phosphate.

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What happens to the NADH produced in glycolysis?

The NADH generated by glyceraldehyde 3-phosphate dehydrogenase is later used in oxidative phosphorylation to produce ATP, providing energy for the cell

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Phosphoglycerate kinase

The enzyme that catalyzes the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate, generating ATP in the process.

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3-Phosphoglycerate

The molecule produced from the reaction catalyzed by phosphoglycerate kinase.

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Isomerisation

The transfer of a phosphate group within a molecule, changing its chemical structure.

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Phosphoglycerate mutase

The enzyme that catalyzes the transfer of a phosphate group from the 3-position to the 2-position of glycerate.

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2-Phosphoglycerate

The molecule produced from the reaction catalyzed by phosphoglycerate mutase.

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Enolase

The enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate.

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Phosphoenolpyruvate (PEP)

The molecule produced from the reaction catalyzed by enolase, a high-energy phosphate compound that will be used in the next step of glycolysis.

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Allosteric Inhibition of Phosphofructokinase

ATP is a key regulator of glycolysis. High ATP levels inhibit phosphofructokinase, slowing down the process. This is a feedback mechanism that ensures energy production is balanced with cell needs.

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Glycolysis in Brain

Brain cells heavily depend on glycolysis for their energy supply. Unlike other tissues, brain cells can't use fats for energy.

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The Warburg Effect

The Warburg effect describes cancer cells' preference for anaerobic glycolysis, even in the presence of oxygen. This abnormal metabolism allows them to grow and proliferate rapidly.

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Warburg Effect: Diagnostic and Therapeutic Potential

The Warburg effect can be helpful in diagnosing and treating cancer. Monitoring lactate levels and targeting the Warburg effect pathway may hold therapeutic potential.

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Summary of Glycolysis

Glycolysis is a central pathway, present in all tissues, that breaks down glucose for energy. It can operate in both aerobic and anaerobic conditions.

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Glycolysis Products: Aerobic

Under aerobic conditions, glycolysis produces pyruvate, which can enter the mitochondria for further ATP production, yielding more energy.

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Glycolysis Products: Anaerobic

Under anaerobic conditions, glycolysis produces lactate as the end product, yielding less energy than aerobic glycolysis.

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Irreversible ATP production in glycolysis

ATP is an energy currency for cells. The enzyme involved in ATP production during glycolysis is irreversible, meaning it can only proceed in one direction.

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Net ATP yield of Glycolysis

Glycolysis is a metabolic process that breaks down glucose to produce ATP. The early stages of glycolysis require 2 ATP, but the later stages generate 4 ATP, resulting in a net gain of 2 ATP.

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Anaerobic Glycolysis and lactate

When there's limited oxygen, pyruvate doesn't completely break down into CO2, instead it's converted to lactate. This conversion regenerates NAD+ which is necessary for glycolysis to continue.

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What does lactate dehydrogenase do?

Lactate dehydrogenase is an enzyme that catalyzes the reversible conversion of pyruvate to lactate using NADH and H+ ions. It's important for maintaining NAD+ levels in the body.

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Metabolic fates of pyruvate

Pyruvate can be converted to lactate, acetyl-CoA, or ethanol depending on the presence of oxygen and the availability of mitochondria. With oxygen, pyruvate enters the citric acid cycle, but without oxygen, it turns into lactate or ethanol.

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Regulation of glycolysis

Glycolysis is regulated by both allosteric and hormonal mechanisms. Allosteric regulation involves direct interactions of metabolites with enzymes, affecting their activity. Hormonal control involves signals from hormones that influence enzyme activity.

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Feedback inhibition of glycolysis

Feedback inhibition is a type of allosteric regulation where the product of a pathway inhibits an enzyme earlier in the pathway. Phosphofructokinase, a key enzyme in glycolysis, is inhibited by ATP, citrate, and fructose 6-phosphate.

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Allosteric control of phosphofructokinase

Allosteric control of phosphofructokinase involves the binding of molecules like ATP, citrate, and AMP to the enzyme, altering its activity. If the cell has a high energy level (high ATP, high citrate), glycolysis slows down. If the cell needs more energy (high AMP), glycolysis speeds up.

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Net ATP yield of anaerobic glycolysis

The net gain of ATP produced from anaerobic glycolysis is 2 ATP molecules per glucose molecule.

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What is glycolysis?

Glycolysis is the breakdown of glucose into pyruvate.

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What is anaerobic glycolysis?

Anaerobic means without oxygen. Anaerobic glycolysis occurs in the cytoplasm of cells.

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What is ATP?

ATP (adenosine triphosphate) is the primary energy currency of cells. It is used to power various cellular processes.

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Explain the phases of glycolysis.

The process of glycolysis involves a series of enzymatic reactions. It can be divided into two main phases: 1. Energy investment phase: 2 ATP molecules are used. 2. Energy payoff phase: 4 ATP molecules are produced.

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What is the final product of anaerobic glycolysis?

During anaerobic glycolysis, pyruvate is converted to lactate (lactic acid).

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What are the starting and ending molecules of glycolysis?

The process of glycolysis begins with glucose and ends with pyruvate.

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How does the ATP yield of anaerobic glycolysis compare to aerobic glycolysis?

The net gain of ATP from aerobic glycolysis is 38 ATP molecules per glucose molecule. This is significantly more than the anaerobic yield.

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What role does the electron transport chain play in aerobic glycolysis?

The electron transport chain (ETC) is a series of protein complexes that use electrons to generate ATP in aerobic glycolysis.

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How does aerobic respiration compare to anaerobic glycolysis?

The process of aerobic respiration involves glycolysis, the Krebs cycle, and the electron transport chain, all occurring within the mitochondria of the cell.

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Study Notes

Lecture: Glucose metabolism: glycolysis and Anaerobic metabolism

  • The lecture was delivered by Dr. Lauren Albee, from the Department of Biochemistry, King's College London.
  • The lecture focused on glucose metabolism, specifically glycolysis and anaerobic metabolism.
  • Relevant textbook chapters include Chapters 11 (pages 181-187) and 13 (pages 210-215) of Biochemistry and Molecular Biology.
  • The lecture materials are available as an e-textbook at https://bibliu.com/app/#/signinPage.

Learning Outcomes

  • Students should be able to draw structures of glucose and glycogen.
  • Students should be able to outline metabolic events involved in converting glucose to pyruvate through glycolysis.
  • Students should be able to explain ATP formation from ADP through substrate-level phosphorylation.
  • Students should be able to describe NAD+ regeneration from NADH under aerobic and anaerobic conditions, highlighting the role of lactate dehydrogenase in muscle.
  • Students should be able to illustrate a control mechanism in glycolysis regulation.
  • Students should be able to summarize glycolysis's roles in various tissues, such as red blood cells.

Structure and Function of Glucose and Glycogen

  • Glucose: A monosaccharide, approximately 10 g present in plasma. It's osmotically active and a primary immediate energy source, utilized in glycolysis. It's also a precursor for gluconeogenesis.
  • Glycogen: A polysaccharide stored in tissues (approximately 400 g), characterized by low osmolarity and a medium-term energy storage function.

Glycolysis: Key Points

  • Definition: The conversion of glucose (C₆H₁₂O₆) to two molecules of pyruvate (C₃H₄O₃).
  • Location: Cytosol (10 soluble enzymes).
  • Tissues: All tissues.
  • Functions: Energy trapping (ATP synthesis), precursor for fat synthesis, and precursor for amino acid synthesis.

Sources of Glucose for Glycolysis

  • Dietary sugars and starches.
  • Breakdown of stored glycogen in the liver.
  • Recycled glucose from lactic acid, amino acids, or glycerol.

Glycolysis: Summary Diagram (and reactions)

  • This section details the chemical steps involved in glycolysis, showing the sequential conversion of glucose to pyruvate along with various enzymes involved - (chemical structures).

The 10 Reactions of Glycolysis

  • The 10 reactions of glycolysis can be categorized into 4 stages:
    • Activation (using ATP)
    • Splitting the 6-carbon sugar into two 3-carbon units.
    • Oxidation (removing 2 hydrogen atoms).
    • Synthesis of ATP.

Reaction 1 (Trapping Glucose)

  • Hexokinase or glucokinase adds a phosphate group to glucose, trapping it inside the cell.
  • Hexokinase is active in all tissues except the liver, and Glucokinase is active in the liver.

Reaction 2 (Isomerization)

  • A simple isomerization step. Glucose-6-phosphate is converted into fructose-6-phosphate for subsequent reactions via phosphohexose isomerase.

Reaction 3 (Key Regulatory Step - Phosphorylation)

  • Phosphofructokinase is a key regulatory step in glycolysis, and it uses ATP to create fructose 1,6-bisphosphate.

Splitting of the 6-carbon Sugar to 3-Carbon Units

  • Aldolase catalyzes the splitting of fructose-1,6-bisphosphate into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.

Oxidation Step (Reaction 6)

  • Key step where NAD+ is reduced to NADH, along with the production of 1,3-bisphosphoglycerate.

ATP Synthesis Stages (reactions 7-10)

  • A series of reactions where ATP is produced from ADP via substrate-level phosphorylation, focusing on the importance of 1,3-bisphosphoglycerate, 3-phosphoglycerate kinase, and pyruvate kinase.

Reaction 7 (Substrate-Level Phosphorylation)

  • The 1,3-bisphosphoglycerate is converted to 3-phosphoglycerate with a simultaneous production of ATP via 3-phosphoglycerate kinase.
  • This reaction occurs twice for each glucose molecule.

Reaction 8 (Isomerization)

  • A simple isomerization step catalyzed by phosphoglycerate mutase, converting 3-phosphoglycerate to 2-phosphoglycerate. This converts the position of the phosphate group

Reaction 9 (Dehydration)

  • Dehydration reaction by enolase, converting 2-phosphoglycerate to phosphoenolpyruvate.

Reaction 10 (Substrate-Level Phosphorylation)

  • Pyruvate kinase catalyzes the final step, converting phosphoenolpyruvate to pyruvate, producing ATP.
  • This is an irreversible step. This step occurs twice per glucose molecule.

Summary Slide: Yields of ATP from Glycolysis

  • Early stages consume 2 ATP.
  • Later stages produce 4 ATP.
  • Net yield: 2 ATP (plus further ATP from mitochondrial metabolism from 2 NADH).

Anaerobic Glycolysis

  • Low oxygen supply results in converting pyruvate to lactate to achieve NAD+ regeneration.
  • The reaction is catalyzed by lactate dehydrogenase.

Reaction Catalyzed by Lactate Dehydrogenase

  • The reaction is reversible and utilizes NADH, converting pyruvate to lactate.
  • This pathway is critical when oxygen availability is limited.

Metabolic Fates of Pyruvate

  • The metabolic fate of pyruvate depends on the presence or absence of oxygen:
    • Anaerobic conditions: Pyruvate is reduced to lactate.
    • Aerobic conditions: Pyruvate enters the mitochondria to be used in the citric acid cycle. Other pathways include fatty acid synthesis.

Regulation of Glycolysis

  • Primarily under allosteric control (e.g., phosphofructokinase).
  • Hormonal control is also involved, but not discussed in detail in this lecture.

Allosteric Control of Phosphofructokinase

  • The enzyme phosphofructokinase is a key regulator of glycolysis, influenced by allosteric effectors like ATP, ADP, and citrate.
  • Think of cellular energy needs determining whether glycolysis should occur or be inhibited.

Allosteric Inhibition of Phosphofructokinase by ATP

  • High ATP concentrations inhibit phosphofructokinase, slowing the glycolysis reaction rate. This is through its binding to an allosteric site.

Specialized Functions in Tissues

  • Skeletal muscle: Rapid ATP production during intense exercise.
  • Red blood cells: Sole pathway for ATP generation (lacking mitochondria).
  • Brain: Major ATP source (cannot use fats as primary energy).

Summary of Glycolysis

  • Principal catabolic pathway for glucose utilization (occurs in all tissues).
  • Unique capacity for functioning in both aerobic and anaerobic conditions (red blood cells and muscle cells).
  • Low ATP yield but critical for fast energy, and an input for subsequent reactions in the cell.
  • Intermediate products can be used for fatty acid synthesis and other metabolic processes.

Discoveries and Dilemmas

  • "Extras" and topics for further thought and investigation, not part of the required learning for this lecture..

The Warburg Effect

  • Tumour cells exhibit high rates of glycolysis even when mitochondria are present. They produce far more lactate than healthy cells.
  • This effect allows for rapid ATP synthesis and the generation of intermediates for biosynthetic reactions required for rapid cellular growth.

Multiple Choice Questions (MCQs)

  • The document includes MCQ questions covering end products of glycolysis, tissues where glycolysis is essential, anaerobic glycolysis ATP yield, crucial glycolytic reactions, and enzymes involved in substrate-level phosphorylation. Answers are NOT included here.

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