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,