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Introduction to Metabolic Pathways Babylon University College of Pharmacy Second Semester 3Rd Class Biochemistry Assist Prof

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Introduction to Metabolic Pathways Babylon University College of Pharmacy Second Semester 3Rd Class Biochemistry Assist Prof Introduction to metabolic pathways Babylon university College of pharmacy Second semester 3rd class Biochemistry Assist prof. Dr. Abdulhussien M. Aljebory Objectives • Explain the role of catabolic and anabolic pathways in cell metabolism • Distinguish between kinetic and potential energy • Distinguish between open and closed systems • Explain the first and second Laws of Thermodynamics • Distinguish between entropy and enthalpy • Understand the Gibbs equation for free energy change • Understand how “usable” energy changes with changes in enthalpy, entropy, and temperature • Understand the usefulness of free energy How to Read a Chemical Equation • A chemical reaction starts with reactants and finishes with products: C6H1206 + 6O2 6CO2 +6H20 + ENERGY reactant product 6CO2 +6H20 + light C6H1206 + 6O2 • Disturbing either the concentration or the energy of the system alters the chemical equilibrium. Living things NEVER let their reactions go to equilibrium The Energy of Life • The living cell is a miniature chemical factory where thousands of reactions occur • The cell extracts energy and applies energy to perform work • Some organisms even convert energy to light, as in bioluminescence 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 (reactant) and ends with a product • Each step is catalyzed by a specific enzyme Type of metabolic pathways: • Catabolic pathways release energy by breaking down complex molecules into simpler compounds • Anabolic pathways consume energy to build complex molecules from simpler ones • Bioenergetics is the study of how organisms manage their energy resources • Metabolism:The sum of all the chemical processes occurring in an organism at one time • Concerned with the management of material and energy resources within the cell • Catabolic pathways • Anabolic pathways • Energy is the capacity to cause change • Kinetic energy is energy associated with motion – Heat (thermal energy) is kinetic energy associated with random movement of atoms or molecules • Potential energy is energy that matter possesses because of its location or structure – Chemical energy is potential energy available for release in a chemical reaction • Energy can be converted from one form to another • The Laws of Energy Transformation: • Thermodynamics is the study of energy transformations • A closed system, such as that approximated by liquid in a thermos, is isolated from its surroundings • In an open system, energy and matter can be transferred between the system and its surroundings • Organisms are open systems Heat Chemical energy (a) First law of thermodynamics (b) Second law of thermodynamics The First Law of Thermodynamics • According to the first law of thermodynamics, the energy of the universe is constant – Energy can be transferred and transformed – Energy cannot be created or destroyed • The first law is also called the principle of conservation of energy • The Second Law of Thermodynamics: • During every energy transfer or transformation, some energy is unusable, often lost as heat • According to the second law of thermodynamics, every energy transfer or transformation increases the entropy (disorder) of the universe • 10% Rule • Entropy is a measure of disorder, or randomness Biological Order and Disorder • Cells create ordered structures from less ordered materials • Organisms also replace ordered forms of matter and energy with less ordered forms • Entropy (disorder) may decrease in an organism, but the universe’s total entropy increases • A living system’s free energy is energy that can do work when temperature and pressure are uniform, as in a living cell Free-Energy Change, G • The change in free energy (∆G) during a process is related to the change in enthalpy, or change in total energy (∆H), and change in entropy, disorder (T∆S): ∆G = ∆H - T∆S • Only processes with a negative ∆G are spontaneous • Spontaneous processes can be harnessed to perform work Free Energy, Stability, and Equilibrium • Free energy is a measure of a system’s instability, its tendency to change to a more stable state • During a spontaneous change, free energy decreases and the stability of a system increases • Equilibrium is a state of maximum stability • A process is spontaneous and can perform work only when it is moving toward equilibrium ATP molecules • Explain the role of ATP in the cell • Describe ATP’s composition and how it performs cellular work • Explain the importance of chemical disequilibrium • Understand the energy profile of a reaction including: activation energy, free energy change, & transition state • Describe the role and mechanisms of enzymes • Explain how enzyme activity can be controlled by environmental factors, cofactors, enzyme inhibitors, and allosteric regulators • Distinguish between allosteric activation and cooperativity • Explain how metabolic pathways are regulated ATP • Energy molecule used to couple exergonic reactions to endergonic • Nucleotide with three • phosphate groups • attached to the ribose • sugar • ATP has a high G • Energy is released from ATP through the loss of phosphate groups • Catabolic reaction resulting from hydrolysis producing ADP + Pi (inorganic Phosphate) + energy (G = -7.3Kcal/mol in the lab, -13Kcal/mol in the cell) • How ATP works: • Hydrolysis of ATP produces inorganic phosphate that is attached to a molecule involved in an endergonic process • Phosphorylation is the process of ATP transferring phosphate to a molecule • Results in a phosphorylated intermediate that can complete the intended reaction Regeneration of ATP • ATP loses energy when it phosphorylates an intermediate molecule of an endergonic reaction. ATP becomes ADP • Regeneration of ATP occurs when inorganic phosphate (Pi) is bound to ADP utilizing energy supplied by a catabolic reaction • How Do We Maximize Cellular Efficiency? • Use of ATP – ATP is a good energy source because: • It can participate in a many different kinds of reactions within the cell • Usually is directly involved in reactions • Little wasted energy during phosphorylation of an intermediate • Use of enzymes – Decrease randomness of reactions • Regulation of enzymes and, thus, reactions Enzymes • Proteins that assist in chemical reactions may be enzymes – Specific because of conformational shape • Enzymes are catalysts – Catalyst: chemical that changes the rate of a reaction without being consumed – Recycled (used multiple times) • Enzymes reduce the activation energy of a reaction – Amount of energy that must be added to get a reaction to proceed Control of Metabolism • Allosteric Regulation: enzyme function may be stimulated or inhibited by attachment of molecules to an allosteric site • Feedback Inhibition: end product of metabolic pathway may serve as allosteric inhibitor • Cooperativity: single substrate molecule primes multiple active sites increasing activity Exergonic and Endergonic Reactions in Metabolism • An exergonic reaction proceeds with a net release of free energy and is spontaneous • An endergonic reaction absorbs free energy from its surroundings and is nonspontaneous Reactants Amount of energy released (G < 0) Energy Free energy Free Products Progress of the reaction Exergonic reaction: energy released Products Amount of energy required (G > 0) Energy Free energy Free Reactants Progress of the reaction Endergonic reaction: energy required Equilibrium and Metabolism • Reactions in a closed system eventually reach equilibrium and then do no work • Cells are not in equilibrium; they are open systems experiencing a constant flow of materials • Dynamic Equilibrium • A catabolic pathway in a cell releases free energy in a series of reactions ATP powers cellular work by coupling exergonic reactions to endergonic reactions • A cell does three main kinds of work: – Mechanical, Transport and Chemical • To do work, cells manage energy resources by energy coupling, the use of an exergonic process to drive an endergonic one • ATP (adenosine triphosphate) is the cell’s energy shuttle • ATP provides energy for cellular functions How do living organisms create macromolecules, organelles, cells, tissues, and complex higher-order structures? • The laws of thermodynamics do not apply to living organisms. • Living organisms create order by recycling and reusing energy from the sun. • Living organisms create order locally, but the energy transformations generate waste heat that increases the entropy of the universe. Are most chemical reactions at equilibrium in living cells? • yes • no • only the exergonic reactions • all reactions except those powered by ATP hydrolysis A reaction has a G of 5.6 kcal/mol. Which of the following would most likely be true? • The reaction could be coupled to power an endergonic reaction with a G of 8.8 kcal/mol. • The reaction is nonspontaneous. • To take place, the reaction would need to couple to ATP hydrolysis. • The reaction would result in products with a greater free-energy content than in the initial reactants. • The reaction would proceed by itself but might be very slow. True or false: The breakdown of food molecules in the gut does not require coupling of ATP hydrolysis, but enzymes are required to speed up these spontaneous reactions. • true • false, because enzymes change the G to a negative value • false, because enzymes are not required,
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