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Chapter 9Introduction to Metabolism

CHAPTER GLOSSARYActivation energyActive siteAllosteric 異位 enzymeAnabolism 合成代謝Apoenzyme 脢本體Catabolism 分解代謝CatalystCoenzymeDenaturationElectron transport chain (ETC)Endergonic 吸收能量的 reactionEntropy 熵 ; 亂度

EnzymeEquilibriumExergonic 釋出能量的 reactionFeedback inhibitonFree energy changeHoloenzyme 全酵素MetabolismMichaelis constant (Km)Phosphorelay systemProsthetic group 輔基Reducing powerReversible covalent modificationStandard reduction potential

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metabolism is the total of all chemical reactions in the cell and is divided into two parts catabolism ( 分解代謝 ) anabolism ( 合成代謝 )

Figure 9.1 Overview of Metabolism

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Catabolism ( 分解代謝 ) fueling 供給燃料 reactions energy-conserving 保存 reactions provide ready source or reducing power (electrons) generate precursors for biosynthesis

Anabolism ( 合成代謝 )

the synthesis of complex organic molecules from simpler ones requires energy from fueling reactions

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Microbial Metabolism have representatives in all five major nutritional types contribute to cycling of elements in ecosystems

some cycling reactions performed only by microbes

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Microbial Cells Must Do Work

chemical work synthesis of complex molecules

transport work take up of nutrients, elimination of wastes, and maintenance of

ion balances mechanical work

cell motility and movement of structures within cells

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The Laws of Thermodynamics thermodynamics

a science that analyzes energy changes in a collection of matter called a system (e.g., a cell)

all other matter in the universe 宇宙 is called the surroundings 環境

First Law of Thermodynamics energy can be neither created nor destroyed total energy in universe remains constant

However, energy may be redistributed either within a system or between the system and its surroundings

Second Law of Thermodynamics physical and chemical processes proceed in such a way that

the disorder of the universe increases to the maximum possible entropy 熵

amount of disorder in a system Heat is released by one chemical reaction and absorbed by

another

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Energy Units

calorie (cal) amount of heat energy needed to raise 1 gram of water from

14.5 to 15.5°C joules (J)

units of work capable of being done by a unit of energy 1 cal of heat is equivalent to 4.1840 J of work

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Free Energy and Reactions

G = H - TS expresses the change in energy that can occur in chemical

reactions and other processes used to indicate if a reaction will proceed spontaneously

if G is negative, reaction is spontaneous if G is positive, reaction is not spontaneous

G free energy change amount of energy available to do work

H change in enthalpy (heat content; 焓 , 熱含

量 ) T

temperature in Kelvin S

change in entropy 熵

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Chemical equilibrium equilibrium

A + B C + D reaction is at equilibrium when rate of forward reaction = rate of

reverse reaction equilibrium constant (Keq)

expresses the equilibrium concentrations of products and reactants to one another

Standard free energy change (Go)

free energy change defined at standard conditions of concentration, pressure, temperature, and pH

Go´ standard free energy change at pH 7 directly related to Keq

Go´ = -2.303RT•logKeq

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Go and Equilibrium

Exergonic reactions

Go´ is negative

(reaction proceeds spontaneously)

Endergonic reactions

Go´ is positive

(reaction will not proceed spontaneously)

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Energy Currency of the CellAdenosine 5’-triphosphate (ATP)

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Role of ATP in Metabolism

The cell’s energy cycle

high energy molecule exergonic breakdown of ATP is coupled with

endergonic reactions to make them more favorable

ATP +H2O ADP + Pi + H+

Go´ = - 7.3 kcal/mol

guanosine 5ˈ- triphosphate, cytosine 5ˈ- triphosphate and uridine 5ˈ- triphosphate also supply some energy

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Oxidation-Reduction Reactions and Electron Carriers

many metabolic processes involve oxidation-reduction reactions (electron transfers)

electron carriers are often used to transfer electrons from an electron donor to an electron acceptor

Oxidation-Reduction (Redox) Reactions transfer of electrons from a donor to an acceptor

can result in energy release, which can be conserved and used to form ATP

the more electrons a molecule has, the more energy rich it is

Redox: Two Half Reactions one is electron donating (oxidizing reaction) one is electron accepting reaction (reducing reaction) acceptor and donor are conjugate redox pair

acceptor + ne- donorreduction

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Standard Reduction Potential (E0)

equilibrium constant for an oxidation-reduction reaction

a measure of the tendency of the reducing agent to lose electrons

more negative E0 better electron donor

more positive E0 better electron acceptor

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The greater the difference between the E0 of the donor and the E0 of the acceptorthe more negative the Go´

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Electron Transport Chain (ETC) electron carriers organized into ETC with the first electron

carrier having the most negative E’o as a result the potential energy stored in first redox couple is

released and used to form ATP first carrier is reduced and electrons moved to the next

carrier and so on

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Electron carriers

NAD nicotinamide adenine dinucleotide

NADP nicotinamide adenine dinucleotide

phosphate

located in plasma membranes of chemoorganotrophs in bacteria and archaeal cells

located in internal mitochondrial membranes in eukaryotic cells examples of electron carriers include NAD, NADP, and others

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Electron carriers FAD

flavin adenine dinucleotide FMN

flavin mononucleotide riboflavin phosphate

coenzyme Q (CoQ) a quinone also called ubiquinone

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Electron carriers cytochromes

use iron to transfer electrons iron is part of a heme

group

nonheme iron proteins e.g., ferrodoxin use iron to transport electrons

iron is not part of a heme group

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Enzymes

carry out reactions at physiological conditions so they proceed in a timely manner

enzymes speed up the rate at which a reaction proceeds toward its final equilibrium

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Structure and Classification of Enzymes

some enzymes are composed solely of one or more polypeptides some enzymes are composed of one or more polypeptides and

nonprotein components

protein catalysts have great specificity for the reaction catalyzed and the

molecules acted on catalyst 催化劑

substance that increases the rate of a reaction without being permanently altered

substrates reacting molecules

products substances formed by reaction

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Enzyme structure apoenzyme

protein component of an enzyme cofactor

nonprotein component of an enzyme prosthetic group – firmly attached coenzyme – loosely attached

holoenzyme = apoenzyme + cofactor

Coenzymes often act as carriers, transporting

substances around the cell

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The Mechanism of Enzyme Reactionsa typical exergonic reaction

A + B AB‡ C + D

transition-state complex – resembles both the substrates and the products

activation energy – energy required to form transition-state complex

enzyme speeds up reaction by lowering Ea

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How enzymes lower Ea

by increasing concentrations of substrates at active site of enzyme

by orienting substrates properly with respect to each other in order to form the transition-state complex

two models for enzyme-substrate interaction lock and key and induced fit

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Lock and Key Model of Enzyme Function

The induced Fit Model of Enzyme Function

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The Effect of Environment on Enzyme Activity enzyme activity is significantly impacted by substrate concentration,

pH, and temperature

Effect of [substrate]

rate increases as [substrate] increases

no further increase occurs after all enzyme molecules are saturated with substrate

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Effect of pH and temperature each enzyme has specific pH and temperature optima denaturation

loss of enzyme’s structure and activity when temperature and pH rise too much above optima

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Enzyme Inhibition

Competitive Inhibition of Enzyme Activity

competitive inhibitor directly competes with binding of substrate to active site

noncompetitive inhibitor binds enzyme at site other than active site changes enzyme’s shape so that it becomes less active

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Ribozymes Thomas Cech and Sidney Altman discovered that some RNA

molecules also can catalyze reactions examples

catalyze peptide bond formation self-splicing involved in self-replication

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Regulation of Metabolism important for conservation of energy and materials maintenance of metabolic balance despite changes in

environment

three major mechanisms metabolic channeling regulation of the synthesis of a particular enzyme

(transcriptional and translational) direct stimulation or inhibition of the activity of a critical enzyme

post-translational

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Metabolic Channeling

differential localization of enzymes and metabolites compartmentation

differential distribution of enzymes and metabolites among separate cell structures or organelles

can generate marked variations in metabolite concentrations

Post-Translational Regulation of Enzyme Activity two important reversible control measures

allosteric regulation covalent modification

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Allosteric Regulation most regulatory enzymes activity altered by small molecule

allosteric effector binds non-covalently at regulatory site changes shape of enzyme and alters activity of catalytic site positive effector increases enzyme activity negative effector inhibits the enzyme

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Covalent Modification of Enzymes reversible on and off switch addition or removal of a chemical group (phosphate, methyl,

adenyl) advantages of this method

respond to more stimuli in varied and sophisticated ways regulation on enzymes that catalyze covalent modification adds

second level

Regulation of glutamine synthetase activity by covalent modification

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Feedback Inhibition also called end product inhibition inhibition of one or more critical enzymes in a pathway regulates

entire pathway pacemaker enzyme

catalyzes the slowest or rate-limiting reaction in the pathway

•each end product regulates its own branch of the pathway •each end product regulates the initial pacemaker enzyme•isoenzymes – different enzymes that catalyze same reaction