Glycolysis Quiz Chapter 2

Glucose Metabolism: Glycolysis & Anaerobic Metabolism

• Lecture Focus: Glucose metabolism, specifically glycolysis and anaerobic metabolism
• Lecturer: Dr. Lauren Albee
• Department: Biochemistry
• Resources: Biochemistry and Molecular Biology Chapters 11 (pp. 181-187) and 13 (pp. 210-215). Available as an e-textbook at https://bibliu.com/app/#/signinPage
• Learning Outcomes: Students should be able to:
  • Draw the structures of glucose and glycogen
  • Outline the metabolic events in glucose conversion to pyruvate
  • Explain ATP formation from ADP via substrate-level phosphorylation
  • Describe NAD+ regeneration from NADH under aerobic and anaerobic conditions, including the role of lactate dehydrogenase
  • Provide an example of a control mechanism in glycolysis regulation
  • Summarize the roles of glycolysis across different tissues (e.g., red blood cells)

Structure and Function of Glucose and Glycogen

• Glucose:
  • Monosaccharide
  • Approximately 10 g in plasma
  • Osmotically active
  • Immediate energy source (glycolysis)
  • Synthesized from non-carbohydrate sources (gluconeogenesis)
• Glycogen:
  • Polysaccharide
  • Approximately 400 g in tissue stores
  • Low osmolarity
  • Medium-term fuel source
  • Synthesis and breakdown later discussed

Glycolysis: Key Points

• Definition: Glucose (C₆) to pyruvate (C₃)
• Location: Cytosol (10 soluble enzymes)
• Tissues: All tissues
• Functions: Energy trapping (ATP synthesis); intermediates for fat and amino acid synthesis

Sources of Glucose for Glycolysis

• Sugars and starches from the diet
• Breakdown of stored glycogen from the liver
• Recycled glucose (from lactic acid, amino acids, or glycerol)

Glycolysis: Summary Diagram

• The diagram illustrates the ten reactions of glycolysis, featuring key enzymes, intermediates, and ATP/ADP transformations. Glycolysis is depicted as a sequence of enzymatic reactions involving glucose, glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate, and other intermediates ultimately leading to the production of pyruvate.

Glycolysis: Stages

• Activation (using ATP): Converting glucose to fructose-1,6-bisphosphate, requiring ATP.
• Splitting the 6-carbon sugar: Breaking the 6-carbon sugar into two 3-carbon sugars, yielding glyceraldehyde-3-phosphate.
• Oxidation (removing 2H atoms): Oxidizing glyceraldehyde-3-phosphate, creating NADH and generating energy.
• Synthesis of ATP: Generating ATP through substrate-level phosphorylation.

Reactions 1, 2 &3 (activation stage)

• Reaction 1: Hexokinase or glucokinase phosphorylates glucose to glucose-6-phosphate, trapping it in the cell.
• Reaction 2: Phosphohexose isomerase converts glucose-6-phosphate to fructose-6-phosphate.
• Reaction 3: Phosphofructokinase phosphorylates fructose-6-phosphate to fructose-1,6-bisphosphate, a crucial regulatory step.

Splitting of 6C Sugar to 3C Units

• Aldolase breaks fructose-1,6-bisphosphate into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.

Reactions 4 & 5

• Aldolase catalyzes the cleavage of fructose-1,6-bisphosphate into glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP).
• Triose phosphate isomerase quickly converts DHAP into G3P.

Oxidation Step (Reaction 6)

• Glyceraldehyde-3-phosphate dehydrogenase oxidizes glyceraldehyde-3-phosphate, producing NADH and 1,3-bisphosphoglycerate.
• This reaction marks an oxidative process vital for energy generation in glycolysis.

ATP Synthesis Stages (Reactions 7, 8, 9, 10)

• Reaction 7: Phosphoglycerate kinase produces ATP from 1,3-bisphosphoglycerate.
• Reaction 8: Phosphoglycerate mutase converts 3-phosphoglycerate to 2-phosphoglycerate.
• Reaction 9: Enolase transforms 2-phosphoglycerate into phosphoenolpyruvate (PEP).
• Reaction 10: Pyruvate kinase converts PEP to pyruvate, creating a second ATP molecule.

Reaction 7 - Substrate Level Phosphorylation

• ATP is produced during this step through substrate-level phosphorylation.
• Two ATP molecules are produced for each glucose molecule.

Reaction 8 - Isomerisation

• Phosphoglycerate mutase moves the phosphate group within the substrate, maintaining the pathway.
• This reversible reaction moves a phosphate group, altering the configuration.

Reaction 9

• Enolase catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate by removing water molecules.
• The molecule is dehydrate to form phosphoenolpyruvate (PEP), an important link between glycolysis and other metabolic processes.

Reaction 10 - Substrate Level Phosphorylation

• Pyruvate kinase generates a second ATP molecule through substrate-level phosphorylation.
• It converts phosphoenolpyruvate (PEP) to pyruvate, releasing energy with the formation of ATP.
• Note this step is irreversible.

Summary Slide: ATP Yields

• Early stages use 2 ATP
• Later stages make 4 ATP
• Net yield = 2 ATP (plus further ATP from mitochondrial metabolism)

Anaerobic Glycolysis

• When oxygen availability is limited, pyruvate is converted to lactate.
• This process regenerates NAD+ from NADH, enabling glycolysis to continue without oxygen.
• The production of lactate during anaerobic conditions supports the regeneration of (oxidized) NAD+, essential for continuing glycolysis.

Reaction Catalyzed by Lactate Dehydrogenase

• Lactate dehydrogenase is a reversible enzyme.
• It converts pyruvate to lactate when oxygen is limited, using NADH, releasing energy for the continuation of glycolysis.

Metabolic Fates of Pyruvate

• In the absence of oxygen or mitochondria, pyruvate can be converted into lactate or ethanol.
• When sufficient oxygen and mitochondria are present, pyruvate can enter the citric acid cycle, producing ATP.

Regulation of Glycolysis

• Controlled by allosteric and hormonal mechanisms.
• One example of allosteric regulation: Phosphofructokinase regulation (ATP effects on the enzyme).

Allosteric Inhibition of Phosphofructokinase by ATP

• ATP binding to a regulatory site on the enzyme slows the reaction.
• This is a control mechanism, ensuring that glycolysis is suppressed when sufficient ATP is available.

Specialised Functions in Tissues

• Skeletal muscle: Rapid ATP production during intense exercise.
• Red blood cells: Primary pathway for ATP generation. (No mitochondria)
• Brain: Major energy source for ATP, but it cannot utilize fats as energy sources.

Summary of Glycolysis

• Main catabolic pathway for glucose utilization across all cells.
• Primarily anaerobic, a second ATP production in aerobic conditions.
• Low energy yield (2 ATP) but a crucial pathway, with generated pyruvate entering mitochondria for more significant ATP production.
• Production of intermediates for fatty acid and other metabolic processes.

Discoveries and Dilemmas

• Relevant 'extras' for further consideration, not required for immediate learning.

The Warburg Effect

• Tumour cells show high glycolytic rates, even with functional mitochondria.
• This is a hallmark feature of cancerous growth and is being intensively studied for diagnostic and therapeutic purposes.

Multiple Choice Questions (MCQs)

• Questions related to glycolysis products, relevant cell types, and ATP yields are presented. See pages 35-38 for the specific MCQ questions.