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://antr anik.or g/anabolic-an d-cat aboli c-reactions/ Slide No. 3 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. 4 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 Energy and Work (cont.) 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 To view this video, go to Chapter 10 Animations of Prescott's Microbiology Companion Site (9 th ed.) located at the following URL: http://highered.m he du cati on. co m/si tes /0 073 40 24 00 /st ude nt _vie w0/i nd ex. ht ml 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 To view this video, go to Chapter 10 Animations of Prescott's Microbiology Companion Site (9 th ed.) located at the following URL: http://highered.m he du cati on. co m/si tes /0 073 40 24 00 /st ude nt _vie w0/i nd ex. ht ml To view this video, go to Chapter 10 Animations of Prescott's Microbiology Companion Site (9 th ed.) located at the following URL: http://highered.m he du cati on. co m/si tes /0 073 40 24 00 /st ude nt _vie w0/i nd ex. ht ml 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 (Source: Black 1999) 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 Non-competitive Inhibition Slide No. 39 Slide No. 40 Metabolic Regulation 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 Slide No. 41 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. 42 Dr. Cooper 7
u Post-translational control of enzyme activity regulates many metabolic pathways using several different mechanisms: v Allosteric regulation v Covalent modification v Feedback inhibition [each of these mechanisms is described in further detail on the following slides] 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 Slide No. 44 v Covalent modification 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 Figure 10.19 Slide No. 45 Slide No. 46 Figure 10.20 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 Figure 10.21 Slide No. 47 Slide No. 48 Dr. Cooper 8
To view this video, go to Chapter 10 Animations of Prescott's Microbiology Companion Site (9 th ed.) located at the following URL: http://highered.m he du cati on. co m/si tes /0 073 40 24 00 /st ude nt _vie w0/i nd ex. ht ml Slide No. 49 Dr. Cooper 9