Energy - the ability to do work, that is, to move matter against opposing forces such as gravity and friction

• kinetic energy - the energy of motion.
• potential energy - stored energy, the capacity to do work

• The First Law of Thermodynamics - Energy can be transferred and transformed, but it can neither be created nor destroyed
• The total energy of the universe is constant
• Mass is a form of energy (this is only important when considering atomic reactions, so we won't dwell on it here...)
• The Second Law of Thermodynamics - Every energy transfer or transformation increases the entropy of the universe
• There is a trend toward randomness
• Energy must be spent to retain order - this spending of energy usually releases heat, which increases the entropy elsewhere

• It is called "free" energy because this is the energy which can perform work, not because there is no energy cost to the system
• There still ain't no free lunch

• Sometimes called spontaneous, but that doesn't mean that it will occur rapidly
• Burning paper is exergonic, but paper just doesn't ignite when it is exposed to air - it requires an initial input of energy to start the reaction

• Most synthesis reactions are endergonic

• The free energy released from the exergonic process is absorbed by the endergonic process

• Mechanical - beating of cilia, muscle contractions, etc.
• Transport - pumping of molecules and ions across a plasma membrane against their concentration gradient, etc.
• Chemical - pushing endergonic reactions that would not occur spontaneously

ATP - Power To Drive Cellular Work

• Contains three phosphate groups connected to each other in sequence
• The bonds an be broken by hydrolysis
• When the terminal phosphate bond is broken, a molecule of inorganic phosphate (P_i)  is formed
• This forms adenosine diphosphate, ADP + (P_i)
• This generates free energy, which can be used by the cell to do work
• Usually, ATP functions by transferring its phosphate group to another molecule, creating a phosphorylated intermediate.
• This phosphorylated intermediate is usually less stable (more reactive) than the original molecule, which drives the reaction
• Obviously, for the cell to function, ATP must rapidly be regenerated.
• One muscle cell can consume and regenerate over 10,000,000 ATP's a second
• If ATP couldn't be regenerated, humans would have to consume nearly their body weight in ATP each day

Enzymes are protein catalysts

• Actually, some RNA molecules possess enzymatic functions, but well over 99% of all enzymes are proteins
• they do not do the impossible - they only speed up reactions
• they are not consumed in a reaction
• they work for both the forward and the reverse reaction
• they are highly selective

• Initial state transition state final state must overcome an energy barrier

• An enzyme lowers this energy barrier, thus speeding up the reaction

• An enzyme has an active site which holds the reactants in a particular way to facilitate the bonding/bond breaking
• Note: it lowers the activation energy for the forward and the reverse (but not in a proportionate way)
• Lock and Key Hypothesis - there is only one active site which precisely fits the reactants (more or less)

Enzymes are Substrate Specific

• The enzyme binds to the substrate or substrate when there are two or more reactants
• While bound, the catalytic action of the enzyme converts the substrate(s) to product(s)
• An enzyme can distinguish its substrate from similar molecules and even isomers of the same molecule
• Only a restricted region of the enzyme molecule actually binds to the substrate - this is called the active site
• This match is not perfect - as the enzyme and substrate come together, a small conformation change occurs so that the active site fits even more snugly around the substrate
• This is know as an induced fit.  Think of a handshake - as your hands come together, your fingers move to more tightly grasp the other hand.
• When the enzyme and substrate come together, they form an enzyme-stubstate complex
• Held together by hydrogen and/or ionic bonds

• The enzyme and the substrate form the enzyme-substrate complex
• R-groups of the amino acids comprising the active site catalyze the reaction
• They often pull or contort the substrate, temporarily weakening bonds or some configuration
• In reactions with two or more substrates, they can form a template to guide the substrates into the most energy-efficient configuration
• The active site may also provide a microenvironment more conducible to the reaction, such as providing a pocket of low pH in an otherwise neutral cell
• The rate of enzyme action is proportional to the concentration of the substrate (more substrate, the faster the reaction rate)
• However, saturation can occur

• An enzyme's function is dependent upon its shape, so environmental conditions which affect shape will affect the catalytic properties of the enzyme
• Temperature - a measure of molecular motion
• For most chemical reactions, as temperature increases, reaction rate will increase
• More molecules will possess enough energy to cross the activation energy barrier
• However, as temperature increases, the molecular motion of the enzyme also increases
• The enzyme's active site may become unstable and function poorly
• Once a certain temperature is reached, bonds maintaining the 2^o, 3^o, and 4^o structure of the protein collapse and the protein loses function
• When a protein falls apart like this, it is called a denatured protein
• There is usually a temperature at which the enzyme exhibits peak performance.  This is known as the temperature optimum for this enzyme.
• The temperature optimum for each enzyme is usually related to the environment in which it will operate
• A DNA polymerase for a human would have a lower temperature optimum than that of a hot springs bacteria

• pH - a measure of [H+] - acidic and basic conditions
• Like temperature, most enzymes have a pH at which they perform at peak efficiency - the pH optimum
• Also like temperature, the pH optimum is related to the conditions in which it will be found
• At extreme pH's, the enzyme may denature

• Cofactors - a non-protein enzyme helper
• aid in enzyme catalytic function
• may be bound tightly to the active site or may be loosely bound
• may be inorganic, such as a zinc or copper ion, or it may be an organic molecule
• if organic, it is commonly called a coenzyme
• most vitamins are coenzymes or provide raw materials for the construction of coenzymes, so take your vitamins!
• Enzyme Inhibitors - chemicals which interfere with enzyme function
• Can be reversible (if hydrogen or ionic bonded) or more-or-less permanent (if covalently bonded to enzyme)
• Some molecules can fit into the active site and may compete for admission into the active site.  These are known as competative inhibitors.
• Other molecules may bind to the enzyme and cause an conformation change which affect the ability of the enzyme to bind to the substrate.  These are known as noncompetative inhibitors
• Enzyme Enhancers - chemicals which increase enzyme function
• Like noncompetative inhibitors, enzyme enhancers can bind to a non-active site and cause a conformation change which enhances enzyme function

• Alter enzyme's shape and function by binding to an allosteric site
• Allosteric site - receptor site on some part of the enzyme remote from the enzyme
• can speed up or slow down enzyme function
• Example - enzymes of catabolic pathways have allosteric sites which can bind ATP and AMP
• ATP is an inhibitor, AMP is an enhancer
• When ATP prodction is greater than use, ATP will accumulate and then slow down or shut off the pathway
• When ATP production lags behind use, AMP will accumulate and enhance the pathway, creating more ATP
• Feedback Inhibition - when the product of a pathway acts as an inhibitor of the pathway
• Prevents too much buildup of product