Metabolism BIOL 3702: Chapter 10 Introduction to Metabolism u Metabolism is the sum total of all the chemical reactions occurring in a cell u Two major parts of metabolism: v Catabolism Ø Large, more complex molecules are broken down into smaller, simpler molecules with the release of energy Ø Fueling reactions Ø Energy-conserving reactions Ø Provide ready source or reducing power (electrons) Ø Generate precursors for biosynthesis Slide No. 1 Slide No. 2 Metabolism (cont.) Energy and Work v Anabolism Ø The synthesis of complex organic molecules from simpler ones Ø Requires energy from fueling reactions http://antranik.org/anabolic-and-catabolic-reactions/ u Energy - the ability to do work u Living organisms carry out three essential types of work using energy: v Chemical - synthesis of complex biological molecules v Transport - uptake of nutrients, elimination of wastes, and maintenance of internal ion balances v Mechanical - change the physical location of organisms, cells, or internal structures Slide No. 3 Slide No. 4 Energy and Work (cont.) Energy and Work (cont.) u Biological energy comes from two main sources v Photosynthesis - process which uses the ultimate source of energy, visible light v Aerobic respiration - breakdown of complex molecules with oxygen as the terminal electron acceptor v Anaerobic respiration and fermentation also contribute to energy production u Much of the energy from these processes is transferred to the structure of adenosine 5 - triphosphate (ATP) which drives work Figure 10.5 Slide No. 5 Slide No. 6 Dr. Cooper 1
Energy and Work (cont.) u ATP is a high-energy molecule and serves as the energy currency of the cell u ATP s energy is stored in the covalent bonds of its two terminal phosphate groups v To form the bonds, energy is required v To break the bonds, energy is released Figure 10.3a Slide No. 7 Slide No. 8 Energy and Work (cont.) u Exergonic breakdown of ATP is coupled with endergonic reactions to make them more favorable Oxidation-Reduction Reactions u Many metabolic processes involve oxidation-reduction ( redox ) reactions (electron transfers) u Electron carriers are often used to transfer electrons from an electron donor to an electron acceptor Figure 10.4 Slide No. 9 Portions Copyright The McGraw-Hill Companies, Inc. and Copyright C. R. Cooper, Jr. Slide No. 10 Oxidation-Reduction Reactions (cont.) u Transfer of electrons from a donor to an acceptor v Can result in energy release, which can be conserved and used to form ATP v The more electrons a molecule has, the more energy rich it is Oxidation-Reduction Reactions (cont.) u Redox reactions can be considered two half reactions v One is electron donating (oxidizing reaction) v One is electron accepting reaction (reducing reaction) v Acceptor and donor are conjugate redox pair Ø Acceptor + e - Ø Donor - e - Portions Copyright The McGraw-Hill Companies, Inc. and Copyright C. R. Cooper, Jr. Slide No. 11 Portions Copyright The McGraw-Hill Companies, Inc. and Copyright C. R. Cooper, Jr. Slide No. 12 Dr. Cooper 2
Electron Transport Chain u Electron carriers are often organized into an electron transport chain (ETC) v Location Ø Plasma membranes of chemoorganotrophs in bacteria and archaeal cells Ø Internal mitochondrial membranes in eukaryotic cells v Examples of electron carriers include NAD, NADP, and others v First carrier is reduced and electrons moved to the next carrier and so on Figure 10.7 Slide No. 13 Slide No. 14 Electron Transport Chain (cont.) u Some common electron carrier molecules important in metabolism: v Nicotinamide adenine dinucleotide Ø Oxidized form - NAD + Ø Reduced form - NADH v Nicotinamide adenine dinucleotide phosphate Ø Oxidized form - NADP + Ø Reduced form - NADPH Slide No. 15 Slide No. 16 Electron Transport Chain (cont.) v Flavin adenine dinucleotide Ø Oxidized form - FAD + Ø Reduced form - FADH v Others involved in many respiratory electron chains Ø Coenzyme Q (ubiquinone) Ø Various cytochromes Ø Nonheme iron proteins, e.g., ferredoxin Figure 10.8 Slide No. 17 Slide No. 18 Dr. Cooper 3
Figure 10.9 Figure 10.10 Slide No. 19 Slide No. 20 Slide No. 21 Slide No. 22 Enzymes u Enzymes are protein catalysts having great specificity for a particular reaction and its reactants v Catalyst increases the rate of a reaction without being permanently altered itself v Reacting molecules are termed substrates v The resulting molecules of a reaction are termed products (Source: Black 1999) Slide No. 23 Slide No. 24 Dr. Cooper 4
u Most enzymes are pure proteins whereas others are a mixture of proteins and other substances u Holoenzyme - complete enzyme consisting of the apoenzyme and its cofactor v Apoenzyme - protein portion v Cofactor - non-protein portion Ø Firmly attached - prosthetic group Ø Loosely attached - coenzyme (Source: Black 1999) Slide No. 25 Slide No. 26 u Six classes of enzymes [Table 10.3] u Mechanism of action v Enzymes increase reaction rates without altering equilibrium constants v In simplest terms, enzymes lower a reaction s activation energy - amount of energy required for reacting molecules to reach the transition state Slide No. 27 Slide No. 28 v Activation energy is lowered through bringing reactants into close proximity with one another and in the proper orientation Ø Active (catalytic) site - special location on the enzyme where substrates bind Ø Enzyme-substrate complex is formed as a result of this binding Figure 10.15 Slide No. 29 Slide No. 30 Dr. Cooper 5
(Source: Black 1999) v Enzymes use two models to perform this function Ø Lock-and-key model - rigid and specific sites Ø Induced fit model - wraps around substrate(s) Lock-and-key model Slide No. 31 Slide No. 32 Induce fit model Induce fit model Figure 10.16 Slide No. 33 Slide No. 34 u Factors that affect enzyme activity: v Substrate concentration Ø Low concentrations - slow reactions Ø Higher concentrations - increase reaction rates until saturation is achieved v ph and temperature Ø Enzymes have ph and temperature optima at which they have maximum activity (often reflects their environmental habitat) Ø Very high ph levels or temperature leads to denaturation of the enzyme, i.e., destruction of the peptide structure Slide No. 35 Slide No. 36 Dr. Cooper 6
u Enzyme Inhibition - activity can be stopped by two distinct mechanisms: v Competitive inhibition - a molecule closely resembling the true substrate competes with it for binding at the active site v Noncompetitive inhibition - a molecule binds to the enzyme at some other portion other than the active site, inducing a conformational (shape) change to the enzyme rendering it inactive or less active Competitive Inhibition Figure 9.18 Slide No. 37 Slide No. 38 u Thomas Cech and Sidney Altman discovered that some RNA molecules also can catalyze reactions v Catalyze peptide bond formation v Self-splicing v Involved in self-replication (Source: Black 1999) Non-competitive Inhibition Slide No. 39 Slide No. 40 Metabolic Regulation Metabolic Regulation (cont.) u Microbes must coordinate metabolism to conserve energy and resources, as well as to maintain metabolic balance u Carbon flow is regulated in three ways: v Controlling the number of enzyme molecules present v Metabolic channeling - localization of enzymes and metabolites v Post-translational control of enzyme activity - stimulating or inhibiting enzymatic function u Metabolic channeling v Microbes utilize compartmentation to segregate particular enzymes and metabolites into different organelles or cell structures to regulate metabolism Ø Provides simultaneous, but separate operation and regulation of similar pathways Ø Coordinates pathways via transport of metabolites and cofactors between cellular compartments v Channeling may occur in compartments Slide No. 41 Slide No. 42 Dr. Cooper 7
BIOL 3702: Chapter 10 Spring 2015 Metabolic Regulation (cont.) u Post-translational control of enzyme activity regulates many metabolic pathways using the following mechanisms: v Allosteric regulation Ø Activity of regulatory enzymes, known as allosteric enzymes, altered by a small molecules (effector [modulator] molecule) Ø Effector binds to a site (regulatory site) separate from the catalytic site changing the enzyme s shape and either Substrate affinity, or Velocity of the reaction Slide No. 43 Figure 10.19 Slide No. 44 Metabolic Regulation (cont.) v Covalent modification (cont.) Ø Some of these same enzymes are allosteric, thereby adding a second level of regulation and giving the enzyme more dynamic properties Ø Also, regulation of enzymes that catalyze the covalent modification can occur, further adding another layer of regulation to a metabolic pathway Slide No. 45 Figure 10.20 Slide No. 46 Portions Copyright The McGraw-Hill Companies, Inc. and Copyright C. R. Cooper, Jr. Slide No. 48 Metabolic Regulation (cont.) v Feedback inhibition Ø Reversible inhibition of a key regulatory enzyme (pacemaker) in a pathway that usually catalyzes the slowest or rate-limiting reaction Ø Typically regulated by the end-product of the pathway in a process known as feedback (end product) inhibition Dr. Cooper Figure 10.21 Slide No. 47 8