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Higher Human Biology Unit 1 Human Cells KEY AREA 6: Metabolic Pathways Human Cells Learning Intentions KEY AREA 6 – Metabolic Pathways 1. Anabolic Pathways 2. Control of Metabolic Pathways 6a) Metabolic Pathways Metabolism can be defined as all the chemical reactions that occur within the human body Metabolic pathways involve the building up and breaking down of molecules Anabolic pathways require energy and involve biosynthetic (building up) processes e.g. building up of amino acids to form proteins Catabolic pathways release energy and involve the breakdown of molecules e.g. breaking down of glucose in glycolysis Anabolic and Catabolic pathways can have reversible and irreversible steps, and alternative routes 6b) Activation Energy The rate of a chemical reaction is indicated by the quantity of chemical change that occurs per unit time Chemical change may involve joining together simple molecules to form more complex molecules (Anabolism) or may involve splitting of complex molecules into simpler ones (Catabolism) The energy needed to break chemical bonds in the reactant chemicals is called the Activation Energy The bonds break when the molecules of the reactant have absorbed enough energy to make them unstable (this is called the Transition State) and the reaction can occur This energy input often takes the form of heat energy and the reaction only proceeds at a high rate if the chemicals are raised to a high temperature Non-catalysed Reaction Catalysed Reaction 6c) Catalysts, Enzymes & Activation Energy A Catalyst is a substance that:- Lowers the activation energy required for a chemical reaction to proceed - Speeds up the rate of a chemical reaction - Takes part in the reaction but remains unchanged at the end of it An Enzyme is a Biological Catalyst that:- Lowers the activation energy required by the reactants to form the transition state - Speeds up the rate of the reaction - Made of Protein 6d) Enzyme Specificity An enzyme contains an active site which is a specific shape (due to the structure and bonding of the amino acids in the polypeptide chain) An enzyme only acts on one substrate because the enzyme is specific to its substrate and the molecules of the substrate are complementary to the enzyme’s active site for which they show an affinity (chemical attraction) After the reaction, the products have a low affinity for the active site and are released, leaving the enzyme free to repeat this process with new molecules of the substrates 6e) Active Site Induced Fit The active site of an enzyme is not a rigid structure. It is flexible and dynamic When a molecule of a substrate enters the active site, the shape of the enzyme molecule and the active site change slightly, making the active site fit very closely round the substrate molecule – this is called induced fit Induced fit ensures that the active site comes into very close contact with the molecules of substrate and increases the chance of the reaction taking place 6f) Orientation of Reactants When the reaction involves two (or more) substrates, the shape of the active site determines the orientation of the reactants. This ensures that they are held together in such a way that the reaction can take place The active site holds the two reactants closely together in an induced fit, then weakens the chemical bonds that must be broken during the reaction. This reduces the activation energy needed to reach the transition state. 6g) Factors affecting Enzyme Action To function efficiently, an enzyme requires a suitable: - - Temperature - pH - Substrate concentration - Enzyme concentration Inhibitors may slow down the rate of an enzyme-controlled reaction or bring it to a halt 6h) Enzymes & Substrate Concentration As substrate concentration increases, rate of reaction increases and then the rate of the reaction remains constant as the active sites are all occupied because the enzyme concentration is the limiting factor 6i) Control of Metabolic Pathways by presence/absence of Enzymes Metabolic pathways can be controlled by 1. Presence of an Enzyme 2. Absence of an Enzyme 3. Key enzymes regulating the rate of a reaction within a metabolic pathway Regulation of a pathway can be controlled by intra and extracellular signal molecules Genes for some enzymes are continuously expressed. These enzymes are always present in the cell and their control involves regulation of their rate of reaction Most metabolic reactions are reversible and the presence of a substrate or the removal of a product will drive a sequence of reactions in a particular direction Often an enzyme can catalyse a reaction in both a forward and a reverse direction. The actual direction depends on the concentrations of the reactants & the products. Enzymes often act in groups or as multi-enzyme complexes e.g. DNA Polymerase and RNA Polymerase 6j) Control of Enzymes by Gene Expression (switching on/off genes) Lactose Metabolism in Escherichia Coli - Lactose sugar is found in milk - Lactose is made of a molecule of glucose and a molecule of galactose - E.coli must break down lactose into glucose + galactose so it can make use of the glucose - E.coli must break down lactose by using the enzyme β-galactosidase - In order to save energy and resources, E.coli only produce the enzyme when it’s needed! Along a section of DNA there is a regulator gene, and then the Lac Operon The Lac Operon of E.coli consists of a operator gene and a structural gene 6k) Lac Operon Absence of Lactose - Regulator gene codes for the production of a repressor molecule - Transcription & Translation occur to form the repressor protein molecule - The repressor combines with the operator gene - The operator gene “switches off” the structural gene - No B-galactosidase is produced 6l) Lac Operon Presence of Lactose - Regulator gene codes for the production of a repressor molecule - Transcription & Translation occur to form the repressor protein molecule - The repressor combines with Lactose - The operator gene is free - The structural gene is “switched on” - B-galactosidase is produced and breaks down LactoseGlucose+Galactose - When all the lactose has been digested, the repressor becomes free again and combines with the operator so the enzyme is no longer produced 6m) Control of Enzyme Action – Signal Molecules Some metabolic pathways (e.g. Glycolysis) operate continuously The genes that code for enzymes involved in continuous pathways are always switched on, so control of these pathways is brought about by regulating enzyme action Signal molecules control (regulate) the action of some enzymes In the Lac Operon, lactose is called a signal molecule as it causes a gene (the structural gene) that is switched off to become switched on (expressed) Signal molecules that originate from within the cell are called intracellular signal molecules Signal molecules that originate from out-with the cell (in the cell’s environment) are called extra-cellular signal molecules 6n) Control of Enzyme Action – Inhibitors An inhibitor is a substance that decreases the rate of an enzyme controlled reaction A Competitive Inhibitor - has a similar molecular structure to the substrate - competes with the substrate for the active sites on the enzyme - blocks the active sites, so the rate of the reaction decreases Competitive Inhibition can be reversed by increasing the substrate concentration 6o) Control of Enzyme Action – Inhibitors A Non-Competitive Inhibitor - does not have a similar molecular structure to the substrate - does not combine directly with the active site - attaches to a non-active (allosteric) site and changes the shape of the enzyme molecule – indirectly altering the shape of the active site so the rate of the reaction decreases 6p) Control of Enzyme Action - Regulators Enzymes have active sites and nonactive (allosteric) sites Enzymes can change their shape if regulatory molecules bind to a nonactive (allosteric) site If the regulatory molecule is an activator, the enzyme changes to its active state and enzyme activity is stimulated As activator molecules increase, the enzyme reaction rate increases If the regulatory molecule is a noncompetitive inhibitor, the enzyme changes to its inactive state and enzyme activity is inhibited As inhibitor molecules increase, the enzyme reaction rate decreases 6q) Control of Enzyme Action - Feedback Inhibition Feedback inhibition is when the end product binds to an enzyme that catalyses a reaction early in the pathway, which in turn regulates the pathway. This pathway is kept under finely tuned control by negative feedback Feedback inhibition prevents waste of resources Human Cells Questions KEY AREA 6 – Metabolism and Enzymes 1. Testing Your Knowledge 1 Page 85 Q’s 1-4 2. Testing Your Knowledge 2 Page 96 Q’s 1-4 3. Quick Quiz