An Introduction to Metabolism

1. An Introduction to Metabolism Chapter 8

2. METABOLISM • Totality of an organism’s chemical reactions • Arises from interactions between molecules within the cell • These interactions are arranged into pathways • A metabolic pathway begins with a specific molecule that is altered through a series of steps, creating a specific product • Each step in the pathway is catalyzed by a specific enzyme

3. METABOLISM • Enzyme regulation balances metabolic supply and demand – manages the material and energy resources of the cell • Metabolic pathways that break down molecules and release energy are Catabolic Pathways • Cellular Respiration • Metabolic pathways that build up molecules, using energy, are Anabolic Pathways (also called biosynthetic pathways) • Synthesis of proteins from amino acids

4. ENERGY • Energy – the capacity to cause change • Kinetic Energy – Energy associated with motion • Thermal Energy – Kinetic energy associated with the movement of molecules • Potential Energy – Energy that matter possesses because of its position or location or structure (as in atoms) • Chemical Energy – potential energy available for release in a chemical reaction

5. ENERGY TRANFORMATION • Thermodynamics – the study of the energy transformations that occur in matter • 1st Law of Thermodynamics (Principle of Conservation of Energy) • Energy can be transferred and transformed, but it cannot be created or destroyed • 2nd Law of Thermodynamics • Every energy transfer or transformation increases the entropy of the universe • Entropy is a measure of disorder and randomness

6. FREE-ENERGY CHANGE • Free-energy – the portion of a system’s energy that can perform work when temp and pressure are uniform throughout the system (ie. A cell), written G, change in G is ΔG • ΔH is the change in enthalpy (in biological systems, this is equal to change in total energy) • ΔS is a change in the system’s entropy • T is the absolute temperature in Kelvin (K=°C+273) • ΔG = ΔH - TΔS

7. FREE ENERGY CHANGE • ΔG = ΔH – TΔS is important because it can help to determine which reactions will occur spontaneously (without help) • This is an important principal in metabolism especially with regard to supplying energy for cellular work • When spontaneous, ΔG is negative, signifies a loss of energy during the change from initial to final state • Can also be written: • ΔG = ΔG final state – ΔG initial state

8. FREE ENERGY AND STABILITY • Free energy is a measure of system’s instability • As a reaction proceeds towards equilibrium, the free energy of the mixture of reactant and products decreases • Equilibrium will equal the lowest possible G value in the system • Any move away from equilibrium will not be spontaneous and thus will be a positive ΔG

9. FREE ENERGY AND METABOLISM • Exergonic reaction – net release of free energy • ΔG is negative, thus occur spontaneously • Magnitude of ΔG represents the MAXIMUM amount of work the reaction can perform (some energy is released as heat and cannot do work)

10. FREE ENERGY AND METABOLISM • Endergonic reaction – absorbs free energy from its surroundings • Stores free energy (G increases) • ΔG is positive, nonspontaneous • Example: Plants convert light energy to chemical energy through endergonic reactions and then go through several exergonic steps to convert it to sugar

11. EQUILIBRIUM AND METABOLISM • Reactions in isolated systems eventually reach equilibrium • Cells are not in isolation and do not reach metabolic equilibrium – if they did they would die • There is a constant flow of materials in and out of the cell keeping the pathways running • Key to lack of equilibrium – products of one reaction are often used in the next reaction

12. WORK DONE BY CELL • Cells do 3 main types of work • Chemical Work • The pushing of endergonic reactions (that don’t occur spontaneously) • Transport Work • The pumping of substances across the membrane against the direction of spontaneous movement (active transport) • Mechanical Work • The beating of cilia, the contraction of muscle cells, and the movement of chromosomes during cell division

13. ATP • ATP (Adenosine triphosphate) is composed of a ribose sugar, nitrogenous base adenine and a chain of 3 phosphate groups • Energy molecule and nucleoside triphosphate used to make RNA • Bonds in phosphate group can be broken via hydrolysis • This is an exergonic reaction and releases energy

14. ATP • ATP Hydrolysis does not directly do the necessary cellular work, instead ATP releases the energy and proteins use that energy to carry out these jobs • If the ΔG of an endergonic reaction is less than the amount of energy released when ATP is hydrolyzed, then the 2 reactions can be coupled and the overall reactions are exergonic • Often times reactions are coupled, this occurs when ATP is hydrolyzed. The ‘lost’ phosphate group then attaches to another molecule causing it to be more reactive

15. ATP • There is an ATP cycle that allows for ATP to be hydrolyzed creating ADP and then having ADP be phosphorylated to re-create ATP • This process occurs very quickly • Approximately 10 million ATP molecules per second per cell in muscles • Phosphorylation of ADP back to ATP is an endergonic reaction

16. ENZYMES AND ENERGY BARRIERS • An enzyme is a macromolecule that acts as a catalyst, thus speeding up reactions without being consumed by the reactions • Activation energy is the energy required to start a reaction • Transition state is an unstable state where bonds can be broken The activation energy provides a barrier that determines the rate of the reaction. The reactants must absorb enough energy to reach the top of the activation energy barrier before the reaction can occur

17. ENZYMES AND ENERGY BARRIERS • Enzymes catalyze a reaction by lowering the activation energy • They cannot change the ΔG for a reaction or make an endergonic reaction exergonic • They quicken reactions that would occur anyway eventually • Enzymes are specific for the reactions they catalyze

18. SPECIFICITY OF ENZYMES • Substrate – the reactant an enzyme acts upon • Enzyme bonds forming an enzyme-substrate complex • While enzyme and substrate are joined, the enzyme converts the substrate into the product • The reaction catalyzed is specific to each enzyme/substrate relationship; enzymes can recognize substrates specifically even from isomers

19. LOWERING ACTIVATION ENERGY • Enzymes have a variety of ways in which they help speed up reactions • The active site of an enzyme provides an area to properly orient for a reaction when 2 or more reactants are involved • Enzymes can help take a substrate towards its transition state and prepare the molecule for breaking bonds via stretching and distortion • May provide a environment that is more conducive to the reaction • Direct participation of the active site in the chemical reaction

20. EFFECTS ON ENZYME ACTIVITY • Each enzyme has optimal conditions which allows it to perform at its best • Particularly important are pH and temperature • Cofactors – a nonprotein helper for catalytic activity also called coenzymes when this is an organic molecule

21. EFFECTS ON ENZYME ACTIVITY • Enzyme Inhibitors – bonding by covalent bonds generally irreversibly inhibits that enzyme; weak bonds are reversible • Competitive Inhibitors – mimic the substrate, competing for the active sites and reducing the functionality of the enzyme • Noncompetitive Inhibitors – bind to another part of the enzyme, changing the shape and making the active site less effective

22. REGULATION OF ENZYME ACTIVITY • Allosteric Regulation of Enzymes • A protein’s function at one site is affected by the binding of a regulatory molecule to a separate site, causing either inhibition or stimulation • Allosterically regulated enzymes tend to be constructed of 2 or more subunits, each with an active site • Activator – stabilizes the shape of the active sites • Inhibitor – stabilizes the inactive form • A shape change in one site is transmitted to the other subunits

23. REGULATION OF ENZYME ACTIVITY • Cooperativity – the binding of a substrate to one of the active sites stabilizes all of the active sites within the enzyme • Example: Hemoglobin while not an enzyme employs the same method when forming with oxygen

24. REGULATION OF ENZYME ACTIVITY • Feedback Inhibition – a metabolic pathway is switched off by the inhibitory binding of its end product to an enzyme that acts early in the pathway • Example: ATP in an ATP generating pathway

25. ENZYME LOCATION • Enzymes and substrates tend to be found within specific locations within the cell • May be parts of specific membranes • May be located within specific organelles, etc.