metabolic processes enzymes, energy and chemical reactions
TRANSCRIPT
Metabolic Processes
Enzymes, Energy and Chemical Reactions
Cellular Energy Processing•Metabolism: the sum of all chemical reactions–Anabolism: assembly, polymerization, etc.•requires energy
–Catabolism: disassembly, depolymerization•releases energy
–some reactions couple anabolism with catabolism
–catabolism drives all anabolism–all reactions depend on enzyme catalysts
Energy can be stored or used for workFigure 6.1
Cellular Energy Processing
•cellular processes change chemical structures & transport materials–change and movement require energy exchanges
–energy exchanges have to follow the law(s)
Cellular Energy Processing
•First Law of Thermodynamics–during any event, Initial Energy = Final Energy
…neither created nor destroyedFigure 6.2
Cellular Energy Processing
•First Law of Thermodynamics–during any event, Initial Energy = Final Energy
•Second Law of Thermodynamics–during any event, some energy is unavailable to do work
…some is unusable; disorder increases
Figure 6.2
Cellular Energy Processing
•cells obtain energy from outside sources
…an external source is required
Figure 6.2
Total energy =Figure 6.2
Cellular Energy Processing
total energy = usable energy + unusable energy, or
enthalpy = free energy + (entropy · absolute temperature)
H=G +TS, so, G=H-TS (three unmeasurable variables)
G=H-TS (change in free energy at constant temperature)
G > 0; energy requiredFigure 6.3
Cellular Energy Processing G=H-TS describes energy changes in chemical reactions
positive G describes an energy-requiring reaction; anabolism; decrease in entropy
negative G describes an energy-yielding reaction; catabolism; increase in entropy
G < 0; energy releasedFigure 6.3
Cellular Energy Processing spontaneity (≠ rate)
a spontaneous reaction goes more than half way to completion without an energy input; it is exergonic; G < 0
a nonspontaneous reaction goes less than half way to completion without an energy input; it is endergonic; G > 0
if A=>B is exergonic, B=>A is endergonic
Cellular Energy Processing
reactions are reversibleA <=> B
add more A, increase => rateadd more B, increase <= rateequilibrium occurs when rates are equal
the closer to completion equilibrium occurs, the more free energy is released
reversible reaction at equilibriumFigure 6.4
ATP: the
cell’s
chief energy curren
cyFigure 6.5
cellular respirati
on supplies ATP for
anabolismFigure 6.6
ATP hydrolysis coupled to glutamine synthesisFigure 6.7
cellular energy transfer Adenosine TriPhosphate (ATP) is the predominant energy currency in the cellATP hydrolysis is exergonic (G = -7.3 kcal/mol)ATP + H2O => ADP + Pi
ATP synthesis is endergonicATP shuttles energy from exergonic reactions to endergonic reactions
each ATP is recycled ~10,000 times/day~1,000,000 ATPs are used by a cell/second
Enzymes: Biological Catalysts
a catalyst: increases the reaction rate; is unchanged by the reactionmost biological catalysts are proteins
some (few) biological catalysts are ribozymes (RNA)
Ea
determines the likelihood
that a reaction will occurFigure 6.8
Enzymes: Biological Catalysts
each chemical reaction must overcome an energy barrier - activation energy (Ea)spontaneous reactions will go - eventuallythe direction is predictableneither likelihood, nor rate is predictable
heat may supply
Ea
Figure 6.9
E + S => E-S complex => E + P
Figure 6.10
position substratesFigure 6.12
induce strain
alter surface charge
Enzymes: Biological Catalysts
how to overcome the energy barrier?increase kinetic energy of reactant molecules, or
decrease Ea
an enzyme binds a specific substrate molecule(s) at its active siteE + S => E-S complex => E + Pthe active site > positions reactants, strains bonds, etc. to destabilize the reactants…
…lowering Ea
enzyme: lowers Ea, doesn’t change GFigure 6.11
Enzymes: Biological Catalysts
enzymes…efficiency experts of the metabolic worldlower activation energydo not alter equilibrium
increase the rates of forward and reverse reactions
Enzymes: Biological Catalysts
substrate concentration affects reaction rateas increased [reactant] increases reaction rate
so increased [substrate] increases reaction rateuntil…
all active sites are occupied
the reaction is saturated
enzymatic reactions may be saturatedFigure 6.16
induced fit in hexokinaseFigure 6.14
Enzymes: Biological Catalysts
enzyme structure determines enzyme functionthe active site fits the substrate“lock & key”“induced fit”
the rest of the enzyme stabilizes the active siteprovides flexibility
Figure 6.15
Enzymes: Biological Catalysts
enzyme structure determines enzyme functionsome enzymes require non-protein groupscofators: reversibly-bound ions
coenzymes: reversibly bound organic molecules
prosthetic groups: permanently bound groups
Table 6.1
Enzymes & Metabolism metabolic regulation coordinates the many potential enzymatic reactionssequential reactions form pathways
product of 1st reaction is substrate for 2nd
E1 E2 E3 E4
A=> B=> C=> D=> product of pathway
regulation of enzymes in the pathway regulates the entire pathway
related to Sarin gas and malathion
irreversible inhibition by DIPF
Figure 6.17
Enzymes & Metabolism metabolic regulation coordinates the many potential enzymatic reactionsenzyme inhibitors provide negative controlartificial inhibitors can be pesticidesirreversible inhibition - covalent modification of active site
natural metabolic regulation is often reversiblecompetitive inhibition
cartoon
version
Figure 6.18
Enzymes & Metabolism metabolic regulation coordinates the many potential enzymatic reactionsenzyme inhibitors provide negative controlartificial inhibitors can be pesticidesirreversible inhibition - covalent modification of active site
natural metabolic regulation is often reversiblecompetitive inhibitionnoncompetitive inhibition
cartoon
version
Figure 6.18
Enzymes & Metabolism metabolic regulation coordinates the many potential enzymatic reactionsallosteric enzymes have catalytic and regulatory subunits
active and inactive enzyme conformations are in equilibrium
Figure 6.19
•
Figure 6.20
Enzymes & Metabolism metabolic regulation coordinates the many potential enzymatic reactionsallosteric enzymes regulate many metabolic pathwayscatalyze first committed steprespond sensitively to inhibition
often inhibited by pathway end product - “end-product inhibition”
end-product inhibition by isoleucineFigure 6.21
Enzymes & Metabolism metabolic regulation coordinates the many potential enzymatic reactionsallosteric enzymes regulate many metabolic pathwayscatalyze first committed steprespond sensitively to inhibitionoften inhibited by pathway end product - “end-product inhibition”saves resources when end product is sufficient
secondary & tertiary structures
depend on are disrupted by
H-bonds heat
ionic interactions
pH changes
hydrophobic interactions
detergents
disulfide bonds red/ox changes
pH optima for three enzymes
Figure 6.22
temperature optimumFigure 6.23
Enzymes & Metabolism enzyme activity relies on proper environmental conditionssome enzymes have isozymes suited to different environmental conditions