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• Principles that govern energy resources
Metabolism/Energy Transformations
p g gyin chemistry, physics and engineering also apply to biology
• Metabolism – all of an organism’s chemical reactions – an emergent property
• Bioenergetics – the study of how organisms manage their energy resources
• Metabolic pathway – alteration of molecules in steps
• Catabolic pathways – breakdown of complex molecules
Chemical reactions in cells are organized into Metabolic Pathways
complex molecules– release energy
• Anabolic pathways – build complex molecules– consume energy– Energy released by catabolic pathways
drives anabolic pathways
Figure 8.2 Transformations between potential and kinetic energy
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Energy transformations of life are subject to two laws of thermodynamics
• Thermodynamics:study of energy transformations
• First law: energy can
Fig. 8.3a
• First law: energy can be transferred or transformed, but cannot be created or destroyed
Chemical energy (e.g., food) is a form of potential energyin molecules because of the arrangement of atoms
Energy transformations of life are subject to two laws of thermodynamics
Second law: every energy transfer or transformation increases the disorder (entropy) of the universe– Entropy: a measure of disorder, or randomness
• The more random a collection of matter, the greater its entropy– Much of the increased entropy of the universe takes the
form of increasing heat• Heat (random molecular motion) is energy in its most random state
Fig. 8.3b
Order as a characteristic of life
• Do living organisms violate the second law of thermodynamics?– NO! Order can increase locally (e.g., a cell), but net effect is
randomization of the universe• Living organisms take in organized forms of matter and
energy, and replace them with less ordered forms
Fig. 8.4
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The relationship of free energy to stability, work capacity, and spontaneous changein systems with higher energy initial states and more stable final states
Initial state – higher energy
.
Free energy change ('G) – portion of a system’s energy that is able to perform work
Fig. 8.5 Final state – more stable
Free energy changes ('G) in exergonic (left) and endergonic (right) reactions
Free energy change ('G) – portion of a system’s energy that is able to perform work (constant T)
'G = 'H – T'S'H = ' total energy (biology); T = temperature (o Kelvin); 'S = ' entropy
At equilibrium, 'G = 0 (cell is dead…)([HUJRQLF�UHDFWLRQ
&DQ SURFHHG VSRQWDQHRXVO\(QGHUJRQLF�UHDFWLRQ
&DQQRW SURFHHG VSRQWDQHRXVO\&DQ�SURFHHG�VSRQWDQHRXVO\ &DQQRW�SURFHHG�VSRQWDQHRXVO\
Fig. 8.6
Equilibrium and work in an isolated (closed) hydroelectric system
Reactions in a system isolated from its surroundings reach equilibrium ('G = 0) and can then do no work
Fig. 8.7
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An open hydroelectric system
Open systems can exchange energy (and often matter) with their surroundings – system does not reach equilibrium
Living organisms are open systemsFig. 8.8a
Figure 8.7c Equilibrium and work in isolated (closed) and open systems
A cell breaking down glucose occurs in a series of reactions that power the work of the cell
Fig. 8.8b
Structure of adenosine triphosphate (ATP)
Fig. 8.9a (also review Chap 4)
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ATP hydrolysis to ADP and Pi
In the cell:'G ~ -13 kcal/mol
Fig. 8.9b (also review Chap 4)
The ATP cycle
In the cell:'G ~ -13 kcal/mol
Fig. 8.12
ATP hydrolysis drives cellular work
TransportExample: ion pumping across membranes (Na+, K+, Ca2+)
Example: pyruvate transport across inner mitochondrial membrane
Mechanical workExamples: cilia beating, muscle contraction, chromosome movement
ChemicalExample: polypeptide synthesis Fig. 8.11
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Energy coupling using ATP hydrolysis
Endergonic ('G > 0)
Coupled reactions:net reaction is exergonic ('G < 0)
Fig. 8.10
'G = -7 kcal/mol
Hydrolysis of sucrose
Fig. 8.13 –Energy profile of an
EXERGONIC reactionDoes this reaction occur spontaneously?Yes…But…VERY slowlyHigh activation energy (EA)EA - extra energy required to start a reaction
EXERGONIC reaction
�(1=<0(6�DUH�ELRORJLFDO�FDWDO\VWV� • Catalyst – changes
reaction rate without being consumed (changed)– Enzyme – a
catalytic protein
• Enzymes speed reactions by lowering EA– Enables transition state to be reached at cell temperature
• Enzymes do not change 'G• Enzymes only affect the reaction rate
Fig. 8.14
– Ribozyme – a catalytic RNA (lectures on: polypeptides; translation)
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• Substrate – reactant that binds to an enzyme• Substrate binds to active site of enzyme
– Structure of active site ĺ specific for substrate binding/catalysis
• Substrate converted to products (may be reversible)
Enzymes are substrate specific
(enzyme that hydrolyzes sucrose)
Enzyme +Substrate
Enzyme-substratecomplex
Enzyme +Products
Induced fit between an enzyme and its substrate:glucose binding to active site of hexokinase
Fig. 8.15
Active site and catalytic cycle of an enzyme
A + B ļ C + D
Fig. 8.16
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• Substrates are typically held in the active site by weak interactions– e.g., H-bonds; ionic bonds
• Catalysis– Thousands of reactions per second– Involves -R groups of a few amino acids at active site
ff d b h i bl ( l !)
Active site is an enzyme’s catalytic center
– Enzymes unaffected by the reaction: reusable (catalyst!)• Most metabolic enzymes catalyze reactions in both
forward and reverse directions– Reversible reactions– Direction (net reaction over many reaction cycles) at any time
depends on the relative concentrations of products and reactants• Concentrations affect 'G
– Enzymes catalyze reactions in the direction of equilibrium
Reaction rate depends on substrate concentration…Michaelis-Menton kinetics…
n
substrate concentration
rate
of r
eact
io
…and enzyme concentration.
n 2 [ ]
substrate concentration
rate
of r
eact
io
1x [enzyme]
2x [enzyme]
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Environmental factors affect enzyme activity
temperature
Fig. 8.17
pH
Inhibition of enzyme activity (some pharmaceuticals, poisons, etc.): COMPETITIVE INHIBITION
Fig. 8.18a,b
Inhibition of enzyme activity (some pharmaceuticals, poisons, etc.):NONCOMPETITIVE INHIBITION
Fig. 8.17a,c
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Allosteric regulation of a multi-subunit enzyme
Most allosterically regulated enzymes contain multiple subunits(multiple polypeptides; quaternary structure)
- each subunit has it’s own active site
Fig. 8.19a
The Evolution of Enzymes
� Enzymes are proteins encoded by genes
� Changes (mutations) in genes lead to changesin amino acid composition of an enzyme
� Altered amino acids in enzymes may result in
© 2014 Pearson Education, Inc.© 2014 Pearson Education, Inc.
y ynovel enzyme activity or altered substrate specificity
� Under new environmental conditions a novelform of an enzyme might be favored
� For example, six amino acid changes improved substrate binding and breakdown in E. coli
Figure 8.19
Active siteTwo changed amino acids werefound near the active site.
© 2014 Pearson Education, Inc.
Two changed amino acidswere found on the surface.
Two changed amino acidswere found in the active site.
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Concept 8.5: Regulation of enzyme activity helps control metabolism� Chemical chaos would result if a cell’s metabolic
pathways were not tightly regulated
� A cell does this by switching on or off the genes that encode specific enzymes or by regulatingthe activity of enzymes
© 2014 Pearson Education, Inc.© 2014 Pearson Education, Inc.
the activity of enzymes
Feedback inhibition in a metabolic pathway for synthesis of isoleucine (an amino acid)
METABOLICMETABOLICPATHWAY
Isoleucine is a non-competitive inhibitor of the
initial step in the pathway
Fig. 8.21
Allosteric Regulation of Enzymes
� Allosteric regulation may either inhibit or stimulate an enzyme’s activity
� Allosteric regulation occurs when a regulatory molecule binds to a protein at one site andaffects the protein’s function at another site
© 2014 Pearson Education, Inc.© 2014 Pearson Education, Inc.
affects the protein’s function at another site
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Figure 8.20a
Regulatorysite (oneof four)
Allosteric enzymewith four subunits Active site
(one of four)
Active formActivator
Stabilizedactive form
(a) Allosteric activators and inhibitors
© 2014 Pearson Education, Inc.
OscillationNon-functionalactive site
InhibitorInactive form Stabilized
inactive form
Cooperativity in an enzyme with multiple subunits
Fig. 8.20b
BSC 2010 Chase
Energy and the Laws of Thermodynamics Motivation: Synthesis of biological macromolecules and the organization (structure) associated with life require continuous input and use of energy (according to the laws of thermodynamics). In the next two lectures, we’ll see how living organisms use specific proteins (enzymes) to transform energy in a highly organized way. Objectives: ¾ Explain the role of catabolic and anabolic pathways in cellular metabolism. ¾ Distinguish between kinetic and potential energy. ¾ Explain why an organism is considered an open system. ¾ Explain the first and second laws of thermodynamics. ¾ Explain why highly ordered living organisms do not violate the second law of
thermodynamics. ¾ Write and define each component of the equation for free energy change ('G). ¾ Distinguish between exergonic and endergonic reactions in terms of free energy change
('G). ¾ Describe the relationship between free energy and equilibrium. ¾ Describe the three main kinds of cellular work. ¾ Describe the structure of ATP and explain in general terms how ATP performs cellular
work. Metabolism Bioenergetics Metabolic pathways
Catabolic pathways Anabolic pathways Energy Chemical energy Thermodynamics First law of thermodynamics Second law of thermodynamics Entropy
BSC 2010 Chase
Free energy
Free energy change ('G) Exergonic reaction Endergonic reaction Adenosine triphosphate (ATP) Energy coupling Phosphorylated intermediate
BSC 2010 Chase
Enzymes and catalysis (Motivation continues from last lecture) Objectives: ¾ Describe the function of enzymes in biological systems. ¾ Explain why an investment of activation energy (EA) is necessary to initiate a
spontaneous reaction. ¾ Explain how enzyme structure determines enzyme specificity. ¾ Describe several mechanisms by which enzymes lower activation energy. ¾ Explain how substrate concentration affects the rate of an enzyme-catalyzed reaction. ¾ Explain how temperature, pH, cofactors, and enzyme inhibitors can affect enzyme
activity. ¾ Explain how metabolic pathways are regulated. ¾ Explain how the location of enzymes in a cell influences metabolism.
Catalyst Activation energy
Enzyme Substrate Product Active site Conformational change Evolution
Activity
Environmental factors Cofactors Inhibitors Activators Allosteric regulation
BSC 2010 Chase
Feedback inhibition Negative feedback Positive feedback Cooperativity
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