An Introduction to Metabolism

 Metabolism = Catabolism + Anabolism  Catabolic reactions are energy yielding They are involved in the breakdown of more- complex molecules into simpler ones  Anabolic reactions are energy requiring They are involved in the building up of simpler molecules into more-complex ones Introduction to Metabolism

“Energy can be transferred or transformed but neither created nor destroyed.” “Every energy transfer or transformation increases the disorder (entropy) of the universe.” Note especially the waste heat First and Second Laws of Thermodynamics

 Organisms take in energy & transduce it to new forms (1st law)  As energy transducers, organisms are less than 100% efficient (2nd law)  Organisms employ this energy to: Grow Protect Themselves Repair Themselves Compete with other Organisms Make new Organisms (I.e., babies)  In the process, organisms generate waste chemicals & heat  Organisms create local regions of order at the expense of the total energy found in the Universe!!! We are Energy Parasites! Energy in the Biosphere

Kinetic and Potential Energy

 First Law of Thermodynamics: Energy can be neither created nor destroyed Therefore, energy “generated” in any system is energy that has been transformed from one state to another (e.g., chemically stored energy transformed to heat)  Second Law of Thermodynamics: Efficiencies of energy transformation never equal 100% Therefore, all processes lose energy, typically as heat, and are not reversible unless the system is open & the lost energy is resupplied from the environment Conversion to heat is the ultimate fate of chemical energy

Downhill Increase stability Greater entropy  G < 0

What is the name of this molecule? Free Energy and Spontaneity

Potential energy Work Spontaneous Equilibrium Forward reaction Equilibrium

Potential energy Work Spontaneous“Food” Forward reaction Waste heat

Note that “Spontaneity” is not a measure of speed of a process, only its direction Movement towards Equilibrium in Steps

Energy released “Food” Movement toward equilibrium Exergonic Reactions

Energy required “Work” Endergonic reactions

Exergonic Reaction (Spontaneous) Decrease in Gibbs free energy (-  G) Increase in stability Spontaneous (gives off net energy upon going forward) Downhill (toward center of gravity well, e.g., of Earth) Movement towards equilibrium Coupled to ATP production (ADP phosphorylation) Catabolism Endergonic Reaction (Non-Spontaneous) Increase in Gibbs free energy (+  G) Decrease in stability Not Spontaneous (requires net input of energy to go forward) Uphill (away from center of gravity well, e.g., of Earth) Movement away from equilibrium Coupled to ATP utilization (ATP dephosphorylation) Anabolism

Coupling Reactions Exergonic reactions can supply energy for endergonic reactions

Energy Coupling in Metabolism Catabolic reaction Anabolic reaction Catabolic reactions provide the energy that drives anabolic reactions forward

Adenosine Triphosphate (ATP)

Energy Coupling via ATP

Hydrolysis of ATP

Coupled Reactions

Various Pi Transfers

Summary of Metabolic Coupling Endergonic reaction Exergonic reaction Endergonic reaction Exergonic processes drive Endergonic processes

Anabolic process Catabolic process Chemically stored energy

Enzyme Catalyzed Reaction Question: Is this reaction endergonic or is it exergonic? Enzyme

Activation Energy (E A ) Anything that doesn’t require an input of energy to get started has already happened!

Low- (i.e., body-) Temp. Stability  Why don't energy-rich molecules, e.g., glucose, spontaneously degrade into CO 2 and Water? To be unstable, something must have the potential to change into something else, typically something that possesses less free energy To be unstable, releasing something’s ability to change into something else must also be relatively easy (i.e., little input energy) Therefore, stability = already low free energy Alternatively, stability = high activation energy  Things, therefore, can be high in free energy but still quite stable, e.g., glucose

Catalysis Lowering of activation energy

Catalysis At a given temperature, catalyzed reactions can run faster because less energy is required to achieve the transition state This is instead of adding heat; heat is an inefficient means of speeding up reactions since it simply is a means of increasing the random jostlings of molecules

Enzyme-mediated Catalysis = Subtle application of energy

Mechanisms of Catalysis  Active sites can hold two or more substrates in proper orientations so that new bonds between substrates can form  Active sites can stress the substrate into the transition state  Active sites can maintain conducive physical environments (e.g., pH)  Active sites can participate directly in the reaction (e.g., forming transient covalent bonds with substrates)  Active sites can carry out a sequence of manipulations in a defined temporal order (e.g., step A  step B  step C)

Catalysis as Viewed in 3D Active site is site of catalysis The rest of an enzyme is involved in supporting active site, controlling reaction rates, attaching to other things, etc.

Induced Fit (Active Site) Induced fit not only allows the enzyme to bind the substrate(s), but also provides a subtle application of energy (e.g., “bending” chemical bonds) that causes the substrate(s) to destabilize into the transition state

Enzyme Saturation Substrate Product Enzyme Activity at Saturation is a Function of Enzyme Turnover Rate

Enzyme Saturation Turnover rate

Non-Specific Inhibition of Enzyme Activity Instability & shape change (too fluid) Reduced rate of chemical reaction Reduced enzyme fluidity Change in R group ionization Denatured? Turnover rate Even at saturation, rates of enzymatic reactions can be modified

Activators of Catalysis Metal Ion or = Organic Molecule = Organic Cofactor

Specific Inhibition Competitive inhibitors can be competed off by supplying sufficient substrate densities Non-competitive inhibitors cannot be competed off by substrate

Allosteric Interactions Reversible interactions, sometimes on, sometimes off, dependent on binding constant and density of effector

Cooperativity Cooperativity is when the activity of other subunits are increased by substrate binding to one subunit’s active site

Feedback Inhibition

Energy-Metabolism Regulation

Enzyme Localization Organization of Electron Transport Chain of Cellular Respiration Enzymes in single pathway may be co-localized so that the product of one enzyme increases the local concentration of the substrate for another

The End