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

Thermodynamics – the study of energy transformation

• 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

Free Energy – the portion of a system’s energy the can perform work

• 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

Exergonic Reaction – a process with a net release of free energy

• 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

Endergonic Reaction – a process which absorbs free energy from the surroundings

• Most synthesis reactions are endergonic

Energy Coupling – the use of an exergonic process to drive and endergonic process

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

Types of Cellular Work

• 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

Useful and much more detailed links

• The First Law of Thermodynamics and Entropy
• The Second Law of Thermodynamics
• Gibbs Free Energy

ATP – Power To Drive Cellular Work

ATP – Adenosine triphosphate – a close relative to Adenine, a nucleotide found in DNA.

• 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 and Chemical Reactions

Catalyst -  a chemical agent that changes the state of a reaction without being consumed in the reaction
Substrate – reactants
Intermediates – compounds formed between initial reactants & products
Products – products
Cofactors- helpers for enzymes (carry e-)
Energy Carriers – sources of quick energy (ATP)

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

How Energy Relates to Reactions

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

Any reaction requires some energy to overcome the activation 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 Catalytic Cycle of an Enzyme

• 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

A Cell’s Physical and Chemical Environment Affect Enzyme Activity

• 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 competitive 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 noncompetitive inhibitors
  • In cells inhibition usually reversible; that is the inhibitor isn’t permanently bound to the enzyme. 
  • Irreversible inhibition of enzymes also occurs, due to the presence of a poison.
    • Penicillin cause the death of bacteria due to irreversible inhibition of an enzyme needed to form the bacterial cell wall.
    • In humans, hydrogen cyanide irreversibly bind to a very important enzyme (cytochrome oxidase) present in all cells, and this accounts for its lethal effect on the body.

• Enzyme Enhancers – chemicals which increase enzyme function
  • Like noncompetitive 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 active site
  • can speed up or slow down enzyme function (enhancers and noncompetitive inhibitors)
  • 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
  • The reaction series converting theronine to isoleucine is a classic example of allosteric regulation. 
  • Five enzymes acting in sequence catalyze the pathway. 
  • The final product of the sequence, isoleucine, acts as an inhibitor of the first enzyme of the pathway, threonine deaminase. 
    
    
    • As the pathway produces isoleucine, any molecules made in excess of cell requirements combine reversibly with threonine deaminase at a location outside the active site. 
    • The combination converts threonine deaminase to the T state and inhibits its ability to combine with threonine. 
    • The pathway is then turned off. 
    • If the concentration of isoleucine later falls as a result of its use in cell synthesis, isoleucine releases from the threonine deaminase enzymes, converting them to the R state in which they have high affinity of the substrate, conversion of threonine to isoleucine takes place.