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Lecture 7: Enzymes and Energetics
I.
A.
1.
2.
Biological Background
Biological work requires energy
Energy is the capacity to do work
a.
Energy is expressed in units of work (kilojoules) or heat energy (kilocalories)
Organisms convert potential energy and kinetic energy
a.
Potential energy is stored energy
b.
Kinetic energy is energy of motion
II.
A.
1.
Laws of thermodynamics governing energy transformations
Total energy in the universe does not change
First law of thermodynamics: Conservation of energy
a.
The total energy of a closed system remains constant
b.
Biological systems are open systems
c.
Organisms can only convert energy to other forms
B.
1.
2.
3.
Entropy of the universe is increasing
In most energy conversions, energy is lost as heat
Entropy may be defined as an increase in disorder or randomness
Second law of thermodynamics
a.
Total amount of entropy (S) increases in the universe as energy is converted from one
form to another
III.
A.
1.
Energy Transformations during Metabolic Reactions
Types of metabolism
Anabolic and catabolic pathways
a.
Anabolism includes synthetic pathways
b.
Catabolism includes reactions in which molecules are degraded
B.
1.
2.
Enthalpy is the total potential energy of a system
Bond energy is the amount of energy required to break a molecular bond
Enthalpy (H) is the total bond energy
C.
1.
Free energy is energy that is available to do cellular work
Free energy is the total energy available to do work
a.
Expressed in kilojoules or kilocalories as G
G is inversely related to entropy
H = G + TS
a.
H is enthalpy
b.
T is the absolute temperature (°K)
c.
S is entropy
d.
When T is constant, E = free energy + entropy (unusable energy)
e.
As the temperature increases, entropy increases
2.
3.
D.
Chemical reactions involve changes in free energy
1.
2.
The Greek letter delta (∆) is used to refer to changes between initial and final states
∆G = ∆H – T∆S
E.
1.
Free energy decreases during an exergonic reaction
The total free energy of a system in the final state is less than the total free energy in the
original state
Exergonic reactions have a –∆G
a.
Exergonic reactions release energy and are spontaneous reactions
b.
These reactions still require activation energies
2.
F.
1.
Free energy increases during an endergonic reaction
An endergonic reaction is one in which there is a gain of free energy
G.
1.
2.
Free energy changes depend on the concentrations of reactants and products
Reactions proceed to a state of dynamic equilibrium
Cellular reactions are typically never at equilibrium
H.
1.
2.
3.
Cells drive endergonic reactions by coupling them to exergonic reactions
Coupled reactions may drive thermodynamically unfavorable endergonic reactions
In energy coupling, one must look at the total ∆G of both reactions
Endergonic reactions are coupled with exergonic reactions
a.
Beakdown of ATP
IV.
A.
Adenosine triphosphate (ATP)
ATP molecule has three main parts
1.
2.
3.
Nitrogen-containing base (adenine)
Ribose, a pentose
3 phosphate groups in a series
B.
1.
ATP donates energy through the transfer of a phosphate group
The bonds linking the 3 phosphate groups may be broken by hydrolysis
a.
These reactions have a large –∆G (–7.6 kcal/mole)
b.
ATP is hydrolyzed to form ADP + Pi
c.
This reaction may be coupled with an endergonic reaction
d.
Phosphorylation reactions occur when the phosphate group is transferred to another
molecule
C.
ATP links exergonic and endergonic reactions
1.
Phosphorylation is coupled to endergonic processes
D.
1.
2.
3.
4.
The cell maintains a very high ratio of ATP to ADP
The actual free energy of ATP under cellular conditions is -10 to -12 kcal/mole
The ratio of ATP to ADP is about 10:1
ATP cannot be stockpiled
A resting human uses about 450 kg (100 lbs.) per day of ATP
a.
Amount present at any given time in the entire body is less than 1 gram (0.03 oz.)
Approximately 10 million molecules of ATP are made and recycled in every cell each second
5.
V.
Redox Reactions
A.
1.
Oxidation
Loss of electrons
a.
Oxidation involves the loss of energy
Reduction
Gain of electrons
a.
Gain of energy
B.
1.
2.
B.
1.
2.
3.
4.
5.
6.
VI.
A.
1.
2.
These processes occur simultaneously, called redox reactions
Most electron carriers carry hydrogen atoms
Electron carriers transfer energy to an acceptor
Electrons lose energy as they are transferred between acceptors
Nicotinamide adenine dinucleotide (NAD+) is a common hydrogen acceptor in respiratory and
photosynthetic pathways
Nicotine adenine dinucleotide phosphate (NADP+) is involved in photosynthesis
Flavin adenine dinucleotide (FAD) is involved in cellular respiration
Cytochromes are proteins containing iron and are also electron carriers
3.
Enzymes are chemical regulators
Most enzymes are protein catalysts
Increase the rate of chemical reactions
Some organic catalysts are enzymes
Nucleotide-based molecules
Enzymes are targets for cellular control
B.
All reactions have a required energy of activation (EA)
C.
1.
An enzyme lowers the activation energy needed to initiate a chemical reaction
Enzymatic action has no effect on the overall free energy
D.
1.
2.
An enzyme works by forming an enzyme-substrate (ES) complex
Enzymes have at least one 3-dimensional area active site
The current model of enzymatic action is the induced-fit model
a.
Active site is not rigid
b.
Binding of the substrate to the active site involves conformational changes in both the
enzyme and (typically) the substrate
c.
The enzyme and substrate form an ES or enzyme-substrate complex
d.
After binding to the substrate, the product is released, and the enzyme can be reused
E.
1.
2.
F.
1.
2.
Naming enzymes
Named for substrate
a.
Names end in -ase
b.
E.g. Sucrase is an enzyme that reacts with sucrose
Other enzymes have older names ending in –zyme
a.
Do not reflect function
b.
E.g. Pepsin and trypsin give
Enzyme specificity
Because of the binding at the active site, the substrate is very specific to the enzyme
Not all enzymes are specific (e.g. lipases react with a variety of fats)
G.
1.
2.
3.
4.
H.
1.
2.
Many enzymes require cofactors
Many enzymes are composed of a protein (an apoenzyme) and a cofactor
Inorganic cofactors include elements such as Mg, Ca, Fe, Cu, Zn, and Mn
Organic non-protein cofactors bind with the enzyme, forming a coenzyme
a.
Coenzymes are typically transfer agents
i.
NADH, NADPH, and FADH2
b.
ATP is a coenzyme
c.
Coenzyme A is important in the transfer of groups derived from organic acids
Most vitamins are coenzymes or are parts of coenzymes
Enzymes are most effective at optimal conditions
Each enzyme has an optimal temperature
a.
In the human body, the optimal temperature for enzymes is near body temperature
b.
High temperatures denature protein enzymes
Each enzyme has an optimal pH
a.
In the human body, the optimal pH for most enzymes is between 6 and 8
b.
A suboptimal pH denatures protein enzymes
I.
1.
Enzymes are organized into teams in metabolic pathways
Enzymes often work in sequences
J.
1.
The cell regulates enzymatic activity
Amount of enzyme produced can control the rate of a reaction
a.
Typically by feedback mechanisms
Allosteric enzymes have a receptor site to which allosteric regulators bind
a.
Some allosteric regulators are inhibitors of the enzyme; others are activators of the
enzyme
2.
K.
1.
2.
Enzymes can be inhibited by certain chemical agents
Reversible inhibition may be competitive or noncompetitive
a.
Reversible competitive inhibition involves a molecule that is structurally similar to the
normal substrate
i.
The inhibitor binds to the active site temporarily
ii.
Reversible noncompetitive inhibition involves binding at a site other than the
active site temporarily (similar to allosteric inhibition)
Irreversible inhibitors permanently inactivate the enzyme
a.
E.g. Nerve gases (cyanide), heavy metals (Hg, Pb)