1. Introduction to Metabolism
Chapter 8
Introduction to Metabolism

2. Energy and Metabolism
Metabolic pathways alter molecules in defined steps
Catabolic – breaking down larger molecules to more simple
Anabolic – consume energy to build up
Bioenergetics – the study of how energy flows through a living organism
Catabolic – cellular respiration,
Anabolic – photosynthesis, protein production

3. Energy Types The ability to do work Kinetic Heat/Thermal Potential
Chemical
Light/Solar(bioluminesence)
Energy is nothing more than the rearrangement of a collection of matter
Living things require the transformation of one energy to another to another to survive
Kinetic – energy of a moving object
Heat/Thermal – kinetic energy associated with the random movement of particles
Potential – energy that matter possesses because of its location or structure
Chemical – potential energy stored within bonds

4. Thermodymanics Study of energy transformation
Follows certain laws/principles
Energy cannot be created nor destroyed or transferred or transformed
Every energy transfer or transformation increases the entropy of the universe
Conservation of energy
Entropy – a measure of the disorder or randomness
As you exercise and convert chemical energy to kinetic energy, you increase the entropy of the system around you – how?
-heat moves molecules, production of small molecules, and the breakdown of large food molecules to smaller more abundant molecules
If a process occurs spontaneously (spontaneous process), it must will increase the entropy of the universe without the input of energy (not fast, just energetically favorable) – some can be fast some can be slow
For a process to occur spontaneously, it must increase the entropy of the universe

5. Energy
Free Energy – the system’s energy that can perform work when temperature/pressure are uniform (ΔG)
Determined by: ΔG = ΔH – TΔS
H – the systems enthalpy (the total energy)
S – the systems entropy
T – the absolute temperature (K)
Spontaneous processes have at –ΔG
Exergonic vs. Endergonic reactions
For delta G to be negative H must be negative or the temperature or disorder must be positive
Spontaneous reactions decrease free energy
Positive free energy results in processes that will not be spontaneous
Think of free energy as a systems desire to become more stable
Unstable systems have high delta G and tend to move to lower delta G – towards equilibrium
As a process moves towards chemical equilibrium, the free energy of the reactants and products decreases – when at equilibirum, no work can be done
Exergonic reactions
Release free energy
Absorb free energy
Glucose to CO2 and H2O releases 686 kcal – exergonic (products contain this energy0
To do the reverse a huge amount of energy must be put in
Metabolism in living systems should never reach equilibrium – if it did cells would be dead
Constant flow of materials in and out of the cell prevent equilibrium
How does a cell prevent equilibrium – have the products become the next reactant in a reaction instead of accumulate

6. Cell Energy Cells perform three types of work: Chemical Transport
Polymers from monomers
Transport
Sodium-Potassium pumps
Mechanical
Cilia and flagellar movment
Exergonic reactions – delta G is negative
Endergonic reactions – delta G is positive and energy is absorbed
Chemical – polymers from monomers
Transport – pumping of substances across membranes
Mechanical – cilia and flagellar movement

7. Cell Energy Adenosine triphosphate (ATP)
Ribose
Adenine
Thee phosphates
Bonds broken by hydrolysis
Exergonic reaction releasing 7.3 kcal
Energy release comes from a chemical change to a state of lower free energy, not the phosphate bonds
The three phosphates are all negatively charged-they are also grouped very closely together (but repel one another) – creates instability
Think of the phosphates like a loaded spring

8. Cell Energy ATP can use one of its phosphates to drive a reaction
Phosphorylated Intermediate
Energy is coupled to drive endergonic reactions
ATP can also be used to regulate protein channels
If the endergonic reaction is less than the amount of energy released by ATP hydrolysis, then the two reactions can be coupled and the reaction becomes exergonic
ATP hydrolysis can change a protein channels shape or can cause actin-myosin complexes

9. Cellular energy ATP has to be regenerated
Endergonic reaction of phosphate to ADP
Energy comes from the breakdown of materials in the cell
Working muscle recycles all of its ATP pool in less than a minute – correlates to 10 million ATP consumed and regenerated per second
Cellular respiration provides the exergonic pathway by which ATP can be regenerated

10. Enzymes Most are proteins Act as biological catalysts
Work to reduce activation energy
Are not consumed during the reaction
Without, many living systems would die
Remember spontaneous does not mean fast, simply no energy input

11. Activation Energy Chemical reactions involve breaking and making bonds
Requires going from stable to unstable back to stable
Energy needed to make unstable – Activation Energy
When new bonds are formed – energy released as heat
Going to an unstable state allows the molecules to absorb energy from their surroundings
Activation energy is often thermal energy that molecules absorb from surroundings – accelerates the molecules so collisions more often – also agitates the atoms in the molecules making the bonds easier to break

12. Enzymes and Activation Energy
Temperatures can make reactants achieve transition state
Not ideal – why?
Enzymes work by lowering the amount of activation energy needed
Simply makes the molecules reach transition state much easier
Too high of heat can denature proteins – heat would also speed up all reactions, not just the one in need
Enzymes do not change the amount of free energy – can’t go from endergonic to exergonic

13. Enzyme Specificity Substrate – the reactants
Active Site – region on the enzyme that binds to the substrate
Formed by a few amino acids
Lock and Key vs Induced Fit models
Enzymes are stiff structures – they are routinely changing shape – the active site slightly changes shape as the substrate enters due to different chemical interactions – like a handshake

14. Enzyme Activity Substrate is held by weak bonds in the active site
Extremely fast acting
One enzyme can work with about 1000 substrate molecules per second
Most reactions are reversible – same enzyme can make either reaction
Hydrogen or ionic bonds
Reaction with the enzyme will proceed in the direction of –delta G

15. Enzyme Activity Enzymes lower activation energy by:
Serving as a template for substrate orientation
Stressing bonds in the substrate and stabilizing the transition state
Providing the proper microenvironment
Participating in the catalytic reaction
Template – the entry into the active site orients the molecules in the proper fashion
Stressing bonds – enzyme may stretch molecular bonds which moves the molecule to the transition state with weaker bonds
Proper microenvironment – some of the amino acids R groups may be acidic if the environment needs this
Participating – a brief covalent bond may form between enzyme and substrate
The rate of the reaction is related to the concentration of the substrate – the more substrate, the more frequently the active site will be accessed

16. Factors Affecting Enzymes
Temperature
Rate will increase to a point
Too high will denature the enzyme pH
Too high/too low – H-bonds or ionic bonds break
Denaturation
Cofactors
Non-protein helpers needed for catalytic reactions
Inhibitors
Competitive vs Noncompetitive
Higher temperatures speed up molecular movement and thus create more collisions
Most enzymes function best degrees C
ph typically between 6-8 – pepsin however works best at 2, and trypsin works best at 8 (odd for a digestive enzyme)
Cofactors can inorganic atoms or can be organic – called co-enzymes
Most vitamins act as coenzymes
Competitive inhibitors reduce the productivity of an enzyme by blocing the substrates from entering the active site
Noncompetitive inhibitors – reduce activity by binding to another part of the enzyme and therefore change shape of the active site
Toxins/poisons are often irreversible inhibitors of enzymes
*Sarin – binds to acetycholinerase (enzyme important to the nervous system)
Antibiotics are sometimes inhibitors of bacterial enzymes – penicillin blocks an active site of an enzyme bacteria use to make the cell wall
4,00 enzymes have been discovered

17. Allosteric Regulation of Enzymes
Regulatory molecules can bind and change the shape of the enzyme
Allosteric Regulation
Much like non-competitive inhibition
Many allosteric regulated enzymes are made of two or more subunits with multiple active sites
Can also have cooperativity – one allosteric molecule binds and thus changes all the active sites thus increasing enzymatic activity