Catalysis
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 and 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 can not change delta G)- 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-substrate 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 conducive 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 average random molecular kinetic energy
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°, 3°, and 4° 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 - pH= -log[H3O+] - 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 coenzymemost 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 is 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
The Control of Metabolism
In many cases, the molecules that naturally regulate enzyme activity behave like reversible noncompetitive inhibitors
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.