Enzymes PDF

Enzymes  Because learning changes everything. ® Chapter 4 Enzymes Human Physiology Sixteenth Edition Stuart Ira Fox Krista Rompolski Copyright 2022 ©...

Enzymes  Because learning changes everything. ® Chapter 4 Enzymes Human Physiology Sixteenth Edition Stuart Ira Fox Krista Rompolski Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. Enzymes Biological catalysts: a. Increase the rate of a reaction b. Are not changed by the reaction (so can be used again) c. Do not change the nature of the reaction--the reaction could have occurred without the enzyme, just much slower d. Lowers the activation energy of the reaction 3 Protein structure revisited Protein structure revisited Reminder: the 3-D shape of a protein is determined by the amino acid sequence of the polypeptide. Mechanisms of Enzyme Activity 1. The function of an enzyme is dictated by its structure. 2. Each enzyme has a characteristic 3D shape or conformation, with pockets that serve as active sites in the enzyme. 6 Mechanisms of Enzyme Activity 3. Reactants are called substrates. Original model: they fit into the active site like a key to a lock (lock-and-key model). 4. Updated model: the initial fit is not exact but will change as the substrate moves into the active site (induced-fit model). Enzymes are very specific to their substrates: Eg. different substrates can’t fit into this enzymes active site, so it won’t catalyze any other reaction other than this one. 7 3D Image of Enzyme ACTIVE SITE Credit: Thomas Shafee [CC BY 4.0 (https://creativecommons.org/licenses/by/4.0)], from Wikimedia Commons Access the text alternative for slide images. 8 Protein structure revisited Reminder: the 3-D shape of a protein is determined by the amino acid sequence of the polypeptide. The amino acids of the active site are particularly important for the enzyme’s function – they bind and/or interact with specific substrate(s) Why the cellular environment is also important for enzyme function: Suboptimal temperatures or pH can denature the enzyme (loss of shape of Mechanisms of Enzyme Activity 5. When a substrate binds to the active site of an enzyme, the substrate forms temporary bonds with the amino acids in the active site, weakening the original bonds of the substrate and allowing them to break more easily. 6. New bonds are formed between substrates as they are brought close together by the enzyme. Bonding of enzyme to substrates forms a temporary enzyme- Access the text alternative for slide images. substrate complex. 10 Mechanisms of Enzyme Activity 7. The enzyme-substrate complex breaks to yield the products of the reaction. Access the text alternative for slide images. 11 Overview of enzyme function https://pdb101.rcsb.org/learn/videos/how-enzymes-work Access the text alternative for slide images. 12 Activation Energy: The energy required for the reactants to engage in a reaction. © 2014 Nature Education Most molecules lack the activation energy for a reaction to happen on it’s own. Catalysts help the reaction occur at lower temperatures. 13 Activation Energy: © 2014 Nature Education 14  Activation energy: Activation energy is the energy © 2014 Nature Education required for a reaction to proceed (the “hump” in the diagram). It causes reactant(s) to become contorted and unstable, which allows the bond(s) to be broken or made. This unstable state is called the transition state. Once in the transition state, the reaction occurs very quickly. Notice on the graph that activation energy is lower if the reaction is catalyzed. 15 How enzymes lower activation energy: © 2014 Nature Education The enzyme can help the substrate reach its transition state in one of the following ways: position two substrates so they align perfectly for the reaction provide an optimal environment, i.e. acidic or polar, within the active site for the reaction contort/stress the substrate so it is less stable and more likely to react temporarily react with the substrate (chemically change it) making the substrate less stable and more likely to react. 16 Complete LP1 Lecture Assignment – Q1 17 Naming Enzymes All enzymes end with the suffix –ase. The first part of the name refers to the enzymes function. E.g. ◦ Phosphatases remove phosphate groups. ◦ Synthetases and synthases catalyze dehydration synthesis. ◦ Hydrolases – promote hydrolysis ◦ Dehydrogenases – remove hydrogen atoms ◦ Kinases – add phosphate groups ◦ Isomerases – rearrange the atoms 18 Enzyme Activity Enzyme activity is measured by the rate at which substrate is converted to product. Factors that alter enzyme activity are: ◦ Temperature ◦ pH ◦ Concentration of cofactors and coenzymes ◦ Concentration of enzyme and substrate ◦ Possible stimulatory or inhibitory effects of products on enzyme function  Effect of Temperature Increasing temperature increases the kinetic energy (movement) of the molecules (they move faster) The molecules are more likely to come into contact with each other for the reaction to take place. So an increase in temperature will increase the rate of reactions in the body until the temperature reaches a few degrees above body  Effect of Temperature If the temperature gets too high, the enzyme becomes denatured: it loses its shape (the tertiary and quaternary structure), the active site no longer fits the substrate, so it no longer functions Decreasing the temperature decreases the kinetic energy of the molecules, so they move slower, are less likely to meet Decrease in temperature will decrease the rate of reactions. Effects of pH Enzymes exhibit peak activity within a narrow pH range called the pH optimum. Extreme pH changes will also denature enzymes (result in enzyme conformational changes) Optimum pH generally reflects the pH of the fluid the enzyme is found in. It is not the same for all enzymes. ◦ Examples of fluids where enzymes are found ◦ Saliva (pH 7) ◦ Small intestine (pH 9) ◦ Stomach (pH 2)  Effect of substrate concentration With enzymes, as the substrate concentration increases, so will the rate of the reaction until the enzyme becomes saturated. Saturated means that every enzyme in the solution is being used to perform reactions as quickly as possible Adding more substrate will not increase the rate of the reaction when saturation is reached Coenzymes and Cofactors Most enzymes need additional small molecules to aid in a reaction. ◦ Coenzymes are organic molecules derived from water-soluble vitamins that aid in enzyme activity ◦ Vitamin B1-12, Vitamin C, Folic acid ◦ They transport hydrogen atoms and other small molecules between enzymes (hydrogen carriers). ◦ Cofactors are inorganic metal ions that aid in enzyme activity ◦ Includes Ca2+, Mg2+, Mn2+, Cu2+, Zn2+ ◦ Cofactors help form the active site through a conformational change of the enzyme or help in enzyme-substrate binding.  Zymogens Enzymes are often produced in an inactive form called a zymogen that is activated when needed ◦The suffix –ogen helps us identify these enzymes ◦ Example: pepsinogen  pepsin Zymogens often require additional enzymes to phosphorylate (e.g. kinases) or dephosphorylate (e.g. phosphatases) their structure to activate it Activation of zymogens during digestion protects the cells from self-digestion when they are produced (e.g. pancreatic cells in pancreas when digestive enzymes are made) Complete LP1 Lecture Assignment – Q2 Access the text alternative for slide images. 26 Law of Mass Action Some chemical reactions are reversible and a single enzyme can perform the reaction in both directions depending on the concentration of substrates and product. ◦When one side of a chemical reaction has a higher concentration than the other, the reaction runs towards the lesser side. This is the law of mass action. E.g. carbonic anhydrase: ◦Water and carbon dioxide can be combined to make carbonic acid, and carbonic acid can be broken back down into water and carbon dioxide. ◦ More carbon dioxide in the blood will drive production of more carbonic acid. ◦ Less carbon dioxide in the blood will shift equation to lower carbonic acid amounts. ◦ It creates and equilibrium of product and substrate. Metabolic Pathways Metabolic pathways are chemical reactions that are linked together in a chain or web. These begin with an initial substrate and end with a final product, with many enzymatic steps along the way. Metabolic Pathways Branched Metabolic Pathways ◦Few metabolic pathways are linear. ◦Most include branches where several products can be produced. Metabolic Pathway Inhibition End Product Inhibition ◦When the end product of a metabolic pathway inhibits a step along the way. ◦Branch points of a pathway are often inhibited by a form of negative feedback in which one of the final products inhibits the branch point Allosteric inhibition: the enzyme. product binds to the enzyme at a location away from the active site, but still changing the shape of the active site so it can no longer bind the substrate. End product inhibition prevents the final product from accumulating.  Metabolic Pathway Errors Inborn Errors of Metabolism ◦ Proteins are coded for on genes in DNA ◦ Inborn errors occur when there is a mutation in a single gene that codes for an enzyme in a metabolic pathway Products to be formed after this enzyme in the chain are not formed. Diseases occur due to loss of end product or accumulation of intermediary products Many inborn errors are lethal to the fetus Metabolic Pathway Inhibition and Errors Laws of Thermodynamics Energy – the capacity to do work Bioenergetics - flow of energy in living systems First Law of Thermodynamics - Energy cannot be destroyed or created, only transformed. ◦ Same as the law of conservation of energy ◦ The transformation from one energy to another is not 100% Second Law of Thermodynamics ◦ Energy is lost as heat with each transformation, so the available free energy (energy available to do work) decreases. Endergonic and Exergonic Reactions Endergonic reactions (Anabolic) ◦Chemical reactions that require an input of energy. ◦Energy required to form bonds (make larger molecules from smaller one) ◦Products contain more free energy than the reactants in the chemical bonds that make them up. ◦ E.g. plants need the energy from sunlight to turn carbon dioxide and water into glucose. It takes energy to organize the carbon dioxide and water into C6H12O6 Endergonic and Exergonic Reactions Exergonic Reactions (Catabolic) ◦Chemical reactions that produce energy. ◦Energy released when bonds are broken (larger molecules are broken down into smaller molecules) ◦Products will have less free energy than the reactants. ◦ E.g. breaking glucose down into carbon dioxide and water produces energy because there is less energy in the bonds of the products than the initial reactant. Complete LP1 Lecture Assignment – Q3 Access the text alternative for slide images. 36 Coupled Reactions: ATP Energy from the environment (food) is ATP produced ATP used for cell work broken down in exergonic (catabolic) reactions to make energy that drives the endergonic (anabolic) reactions in ATP our bodies. Cells can’t use heat, so energy from ADP + Pi ATP exergonic reactions in the body must Food get stored in a usable form: ATP ADP + Pi ◦The chemical bond energy released in exergonic reactions CO2 + H2O ATP ADP + Pi must be directly transferred to ATP ADP + the chemical bond energy in the products of endergonic reactions ADP + Pi Therefore the production of ATP is an endergonic reaction that is coupled to an exergonic reaction to drive it.  Coupled Reactions: ATP ATP is called the universal energy carrier because all cells store and use energy in the form of ATP. The ATP molecule stores energy in its bonds to be used elsewhere. ATP is used as our energy currency and is broken down and built back up repeatedly. When it is made, it is built from ADP and Pi in the following reaction. ADP +  ATP When ATP is used as energy, it is broken down in the following reaction. ATP  ADP +  Coupled Reactions: Oxidation and Reduction Reduction: When an atom or molecule gains electrons (is reduced) Oxidation: When an atom or molecule loses electrons (is oxidized) OIL RIG: Oxidation Is Loss, Reduction Is Gain These reactions are always coupled. For one molecule to lose an Copyright © 2016-2020, tuitiontube.com  Coupled Reactions: Oxidation and Reduction An atom/molecule can be an (Reducing oxidizing agent (helps oxidize agent) the other by being reduced) in one reaction and a reducing agent (helps reduce the other by being oxidized) in another = a series of coupled redox reactions Oxygen is a great electron acceptor (acts as a strong oxidizing agent). (Oxidising agent) Copyright © 2016-2020, tuitiontube.com Coupled Reactions: Oxidation and Reduction In cells, rather than transferring free electrons, hydrogen atoms are transferred instead: ◦A hydrogen atom contains 1 electron ◦A molecule that gains hydrogen is reduced (because the hydrogen atom is carrying electrons with it, the molecule gained electrons). ◦A molecule that loses hydrogen is oxidized (because it loses electrons with the hydrogen that leaves, losing electrons). Coupled Reactions: Oxidation and Reduction Hydrogen carriers (coenzymes) that are used in redox reactions in the body: ◦NAD + = nicotinamide adenine dinucleotide; derived from vitamin niacin (B3) NAD+ + 2H+ ⇌ NADH + H+ ◦FAD = flavin adenine dinucleotide; derived from vitamin riboflavin (B2) FAD + 2H+ ⇌ FADH2 Coupled Reactions: Oxidation and Reduction NAD and FAD are coenzymes: ◦ They accept hydrogens (become reduced) in one enzyme reaction and donate hydrogens (become oxidized) in a different enzyme reaction. ◦ They play an important role in hydrogen transfer for the production of energy in the cell as we’ll see when we discuss glycolysis and the electron transport chain. Complete LP1 Lecture Assignment – Q4 Access the text alternative for slide images. 44  End of Main Content Because learning changes everything. ® www.mheducation.com Copyright 2022 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.