Glycolysis and Metabolic Pathways Quiz

Biological Chemistry 1A - Metabolism

• Metabolism is the process of breaking down and re-synthesizing biological molecules.
• It involves a complex network of enzymatic reactions.
• The number of reactions can exceed 1000, even in organisms as simple as E. coli.
• Imbalances in metabolic processes can affect health and cause disease.

Books

• Students can use the course textbook as a primary resource.
• Additional material, if desired, includes "Biochemistry 7th Edition" by Berg, Tymoczko & Stryer.
• Chapters 15, 16, and 17 are recommended.

Introduction

• Metabolism involves the cycle of food providing energy and building blocks for DNA, protein, and membranes.
• Metabolic processes result in waste products like urea, ammonia, water, and carbon dioxide.
• Metabolic diseases like diabetes, metabolic syndrome, and obesity are major public health concerns.
• Diabetes affected 422 million globally in 2014, with a significant portion of deaths occurring before age 70.
• In the UK, 25% of the population has a BMI of 30 kg/m2 or higher (obesity).

Introduction - Diagram

• A diagram showing the metabolic cycle illustrates the continuous process of food being broken down for energy and the creation of building blocks.
• These building blocks support cellular components such as DNA, proteins, and cell membranes.
• The byproducts of the cycle are waste products such as urea, ammonia, water, and carbon dioxide.

Introduction - Fatty Acid Metabolism

• Understanding fatty acid metabolism is critical for disease control and health improvement.

Definitions

• Catabolism: The breakdown of complex molecules into simpler ones, releasing energy.
• Anabolism: The use of energy to build complex molecules from simpler ones.
• Metabolism: The sum of catabolism and anabolism.
• Cofactor: A non-protein substance, such as an ion or coenzyme, needed for enzyme function.
• Coenzyme: A non-protein organic molecule needed for enzyme function. It usually combines with an apoenzyme to form a complete, functional enzyme.
• Apoenzyme: The protein portion of an enzyme to which a coenzyme attaches to form the active enzyme.

Driving Metabolism - Thermodynamics

• The overall free-energy change (ΔG°) of a series of coupled reactions is equal to the sum of the individual step's free-energy changes.
• A negative ΔG° indicates a spontaneous reaction (occurs naturally).
• A zero ΔG° indicates the system is at equilibrium.
• A positive ΔG° indicates a non-spontaneous reaction (requires energy input).
• Examples of energy sources for metabolic processes include sugars and fatty acids.
• Complete oxidation of glucose releases significant energy (~−2850 kJ/mol).
• Complete oxidation of palmitate, a fatty acid, generates even more energy (~−9781 kJ/mol).

Driving Metabolism - ATP

• ATP (adenosine triphosphate) is a key energy source for cellular processes.
• ATP's structure features phosphoanhydride bonds that release energy when hydrolyzed (broken down).
• Intracellular ATP concentration is tightly regulated (2–10 mM).
• ATP's properties (resonance stabilization, electrostatic repulsion, and metal binding) contribute to its role as an energy currency.

Glycolysis

• Glycolysis is a series of reactions metabolizing glucose to pyruvate, releasing energy.
• It converts a six-carbon glucose molecule into two three-carbon pyruvate molecules.
• It produces two molecules of ATP.
• In humans, glucose in the blood enters cells via specific transporters.

Carbohydrates - Monosaccharides

• Monosaccharides are the simplest carbohydrate units.
• They are classified as either aldoses or ketoses based on the carbonyl group's position.
• Examples include ribose, glucose, and fructose, each with different molecular structures.

Carbohydrates - Polysaccharides

• Polysaccharides are formed from multiple monosaccharides linked together.
• The linkage process creates larger, more complex carbohydrate molecules, such as cellulose.
• Amylose (a starch) is also a polysaccharide.

Glycolysis - Glucose

• Glucose exists in both an alpha and beta form interconverting through mutarotation.
• This cycle involves the opening and closing of the ring structure.

Glycolysis - Overall Process

• Glycolysis involves 10 reactions occurring in three stages.
• The steps in the early stages require energy investment, and subsequent stages produce energy.
• The final product of the pathway is pyruvate; energy is released, stored, and transported.

Glycolysis - Steps

• Glycolysis is a sequence of enzyme-catalyzed reactions converting glucose into pyruvate.
• Detailed pathways of the enzymatic reactions are discussed, showing specific steps and intermediates.

Sources of Glucose

• Dietary sucrose, a disaccharide, is a major source of glucose.
• Sucrose is composed of glucose and fructose.
• Enzymatic processes in the mouth, stomach, and small intestine break down sucrose into its monosaccharide components (glucose and fructose).
• The human body typically consumes approximately 24 kg of sugar per year.

Glycolysis - Step 1

• Glucose phosphorylation into glucose-6-phosphate is catalyzed by hexokinase.
• Hexokinase's active binding site configuration changes form to complete catalysis.
• As part of the conversion, ATP's phosphoanhydride bond is cleaved.
• An aspartic acid residue in the active site acts as a base for glucose’s OH.
• This reaction is thermodynamically favorable because a significantly negative ΔG° change accompanies it.

Glycolysis - Step 2

• An intermediate step in the conversion of glucose into pyruvate is the isomerization of glucose-6-phosphate to fructose-6-phosphate.
• An isomerization reaction converts one molecule into another with the same formula.
• The reaction is catalyzed by phosphoglucose isomerase (PGI).
• The process involves the transformation between a 6-membered sugar ring to a 5-membered sugar ring.

Glycolysis - Step 3

• The next key step is the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate, catalyzed by phosphofructokinase (PFK).
• Allosteric regulation by ATP controls the rate of this reaction.
• The enzyme shows a change in conformation when ATP binds.
• The presence of ATP slows down PFK, affecting the overall rate of glucose transformation to pyruvate.

Glycolysis - Step 4

• A key step in glycolysis is the breakdown of fructose-1,6-bisphosphate into glyceraldehyde-3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP).
• This step is catalyzed by the aldolase enzyme.
• The enzyme reaction is a form of retro-aldol reaction.
• In this step, a larger molecule splits into two smaller molecules.

Glycolysis - Step 5

• Dihydroxyacetone phosphate (DHAP) undergoes isomerization into glyceraldehyde-3-phosphate (GAP) catalysed by triose phosphate isomerase(TIM).
• The reaction converts a ketone to an aldehyde.
• This step is catalyzed by the enzyme triose phosphate isomerase (TIM).

Glycolysis - Summary

• The first five steps of glycolysis transform a glucose molecule into two three-carbon molecules called glyceraldehyde-3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP).
• The next steps produce energy.

NAD

• NAD (nicotinamide adenine dinucleotide) is a coenzyme important in redox reactions.
• It carries electrons between reactions.
• The coenzyme NAD+ was discovered by Arthur Harden in 1906.

Pyruvate - Where it Goes

• Pyruvate branching pathways include acetyl-CoA, lactate, and acetaldehyde.
• Acetyl CoA is a critical fuel source for further oxidation reactions.
• The fate of pyruvate depends on whether the conditions are aerobic or anaerobic.

Pyruvate - Anaerobic Conditions

• Pyruvate is converted to lactate under anaerobic conditions, catalyzed by lactate dehydrogenase (LDH).
• Lactate formation is important for regenerating NAD+.
• Anaerobic conditions arise in muscle tissue during strenuous activity.

Pyruvate - Aerobic Conditions

• Pyruvate is converted to acetyl-CoA under aerobic conditions, an intermediate crucial for the Krebs cycle.

Gluconeogenesis

• Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors, specifically pyruvate.
• It's a pathway crucial during periods of starvation.
• The Cori cycle links gluconeogenesis and glycolysis, with glucose produced in the liver from lactate released by muscles.

Other Compounds from Fermentation

• Microorganisms are used commercially to produce fine chemicals and pharmaceuticals.
• Examples include citric acid (food industry) and penicillin (pharmaceuticals).
• Fermentation technology is an expanding, important sector of biological chemistry.

Ethanol Production from Fermentation

• Fermentation methods account for a significant portion of global ethanol production.
• Other methods for ethanol production exist, such as synthetic production from ethylene.
• Using waste biomass to produce fuel is an increasingly important avenue of research, particularly as fossil fuels become more expensive and scarce.

Additional Notes

• The text mentions various enzymes, including hexokinase, phosphofructokinase, lactate dehydrogenase, pyruvate decarboxylase, alcohol dehydrogenase, and triose phosphate isomerase.
• The text covers relevant details regarding the process of glycolysis.
• The text describes the process of fermentation.
• The text also discusses the concept of thermodynamics in metabolism.
• Key figures, like Hans A. Krebs, are mentioned.