BISC 101 Metabolism & Enzymes PDF

Dr. Onkar S. Bains BISC 101 Concept A: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics Metabolism is the totality of an organism’s chemical reactions Metabolism is an emergent property of life that arises from interactions between molecules wi...

Dr. Onkar S. Bains BISC 101 Concept A: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics Metabolism is the totality of an organism’s chemical reactions Metabolism is an emergent property of life that arises from interactions between molecules within the cell A metabolic pathway begins with a specific molecule and ends with a product Each step is catalyzed by a specific enzyme  Catabolic pathways release energy by breaking down complex molecules into simpler compounds – Catabolic reactions are generally hydrolysis reactions (reactions that use water in order to break chemical bonds so larger molecules can be broken down into smaller molecules) – Example of catabolic reaction: cellular respiration (the breakdown of glucose in presence of oxygen) Anabolic pathways consume energy to build complex molecules from simpler ones – Anabolic reactions (also known as biosynthetic reactions) are generally dehydration synthesis reactions (reactions that release water in order to form bonds so larger molecules can be built) – Example of anabolic reaction: synthesis of protein from amino acids Anabolic reactions require energy from catabolic reactions to synthesize more complex organic molecules Concept B: The free-energy change of a reaction tells us whether or not the reaction occurs spontaneously Biologists want to know which reactions do not require input of energy (i.e., occur spontaneously) and which reactions require input of energy (i.e., occur non-spontaneously) – Some spontaneous processes are instantaneous, such as an explosion…some are very slow, such as the rusting of an old car To do so, they need to determine energy changes that occur in chemical reactions Gibbs free energy (G) of a system is a measure of the amount of usuable energy (energy that can do work) in that system  The change in Gibbs free energy (∆G) during a reaction provides useful information about the reaction’s energetics and spontaneity (where it can happen without added energy) ∆G = Gproducts – Greactants Negative ∆G (∆G0) = reaction is NON-SPONTANEOUS or ENDERGONIC (reactions require input of energy and are therefore NON-FAVORABLE) ∆G at zero = equilibrium  Free energy and metabolism The concept of free -∆G = Gproducts – Greactants energy can be applied to Catabolic reactions the chemistry of life’s are exergonic!! processes An exergonic reaction proceeds with a net release of free energy (ΔG0) from its surroundings and is non- spontaneous  ΔG < 0 ΔG > 0 Exergonic reaction Endergonic reaction Spontaneous reaction Non-spontaneous reaction Reactions require no input Reactions require input of of energy energy Catabolic reactions Anabolic reactions Favorable reactions Non-favorable reactions  Concept C: ATP powers cellular work Most energy coupling in cells is mediated by ATP ATP (adenosine triphosphate) is the cell’s energy shuttle ATP is composed of ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups  The bonds between the phosphate groups of ATP’s tail can be broken by hydrolysis Energy is released from ATP when the terminal phosphate bond is broken – This energy can be used in variety of ways by an organism (i.e., active transport, muscle contraction, etc.) This reaction is referred to as ATP hydrolysis  In the cell, the energy from the exergonic reaction (i.e., ATP hydrolysis) can be used to drive an endergonic reaction This will ultimately lead to an overall reaction that is exergonic  Concept D: Enzymes speed up metabolic reactions by lowering energy barriers Most proteins are enzymes A catalyst is a chemical agent that speeds up a reaction without being consumed (or changed) by the reaction An enzyme is a catalytic protein For example, hydrolysis of sucrose by sucrase is an enzyme-catalyzed reaction  Activation energy barrier In order for the reaction to take place, some or all of the chemical bonds in the reactants must be broken so that new bonds, those of the products, can form To get the bonds into a state that allows them to break, the molecule must be contorted (deformed, or bent) into an unstable state called the transition state  The transition state is a high- energy state, and some amount of energy – the activation energy or free energy or activation (EA) – must be added in order for the molecule reach it EA = difference in free energy between – In general, the transition transition state and reactants state of a reaction is always at a higher energy level than the reactants or products – Activation energy is often supplied in the form of heat that the reactant molecules absorb from the surroundings How enzymes lower the EA barrier Enzymes catalyze reactions by lowering the EA barrier Enzymes do not affect the change in free energy (∆G); instead, they hasten reactions that would occur eventually ΔG -△G +△G Substrate specificity of enzymes The reactant that enzyme acts on is called the enzyme’s substrate Enzyme binds to its substrate, forming an enzyme-substrate complex Active site is the region on enzyme where substrate binds Induced fit of a substrate brings chemical groups of the active site into position that enhance their ability to catalyze the reaction  1 Substrates enter active site; enzyme changes shape such that its active site 2 Substrates held in enfolds the substrates (induced fit). active site by weak interactions, such as hydrogen bonds and ionic bonds. Substrates Enzyme-substrate complex 3 Active site can lower EA and speed up a reaction. 6 Active site is available for two new substrate molecules. Enzyme 5 Products are 4 Substrates are released. converted to products. Products  Enzyme-catalyzed reactions can be saturated Speed of an enzyme-catalyzed reaction … – … increases linearly at low substrate concentrations More active sites are free to bind substrate molecules so that product molecules can be made – … slows as substrate concentration increases – … reaches maximum speed at high substrate concentrations Reaction rates level off (or plateau) because all available active sites are filled (or saturated) with substrate molecules to create product molecules  Components of an enzyme Although some enzymes consist entirely of proteins, most consist of both a protein, called an apoenzyme, and a non-protein component (co-factor) Co-factors may be inorganic (such as a metal in ionic form) or organic – Common inorganic co-factors include copper, iron, zinc, magnesium and calcium An organic co-factor is called a co-enzyme (vitamins are an example)  Apoenzymes are inactive by themselves; they must be activated by co-factors…together the apoenzyme and co-factor form a holoenzyme (whole active enzyme) Co-factors (including coenzymes) are required by certain enzymes to carry catalysis – They bind to the active site but are not considered substrates of the chemical reaction Concept E: Local conditions affect enzyme activity An enzyme’s activity can be affected by: – General environmental factors, such as temperature and pH – Chemicals that specifically influence the enzyme (i.e., inhibitors and activators)  Effects of temperature on enzyme activity Each enzyme has an optimal temperature in which it can function – As the temperature rises, reacting molecules have more and more kinetic energy – This increases the chances of a successful collisions between enzyme and substrate molecules (which means rate of reaction increases) – Reaction rate will peak at an optimal temperature (in humans that is 37oC) – Increasing temperature beyond peak point affects enzyme tertiary structure, thereby leading to denaturation and a sudden decrease in rate of reaction (most types of bonds holding the tertiary structure are broken with high heat)  Effects of pH on enzyme activity Each enzyme has an optimal pH in which it can function – Enzyme's rate of reaction peaks at an ideal pH – In presence of either excess H+ (acidic conditions) or excess OH- ions (basic conditions), ionic bonds and hydrogen bonds holding tertiary structure of enzyme are primarily broken, which means denaturation is initiated – Due to denaturation, the enzyme begins to lose its functional shape…by losing its shape, the active site of the enzyme is distorted or lost, which means that substrate will no longer fit into it (so rate of reaction decreases) OH- δ+ δ- H+ OH- H+ Effects of enzyme inhibitors Competitive inhibitors bind to the active site of an enzyme, competing with the substrate – Competitive inhibitors look structurally similar to substrate – Effect of competitive inhibitor can be overcome by adding more substrate Non-competitive inhibitors bind to another part of an enzyme (allosteric site), causing the enzyme to change shape and making the active site less effective – Non-competitive inhibitors DO NOT look structurally similar to substrate – Effect of non-competitive inhibitor CANNOT be overcome by adding more substrate Examples of inhibitors include heavy metals, toxins, poisons, pesticides, and antibiotics  Feedback inhibition In feedback inhibition, the end product of a metabolic pathway shuts down the whole pathway Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed