Enzymes pp 96 - 102

Enzymes enzyme - biological catalyst, speeds up chemical reactions without being consumed

Enzymes All enzymes are proteins; not all proteins are enzymes. Most enzymes have an –ase ending. The root of the enzyme name suggests what molecule it acts upon. ATPase amylase

Enzymes Enzymes can only speed up reactions which would normally occur anyway. substrate – reactant that binds to enzyme Enzymes bind very specific substrates; often an isomer will not bind. Enzymes which act on glucose will not act on galactose.

Steps to Enzyme Reactions Substrate binds to available active site pocket. Enzyme changes shape to envelope substrate(s) Reaction occurs Products lose affinity for the active site Enzyme is set for another substrate

Substrate Binding active site – pocket in which the substrate binds Q: What part of AAs interact with substrate? A: R-groups  also involved in the t - negative acid group is attracted to the positively charged part of substrate.

Substrate Binding R-groups of amino acids interact with the substrate.

Enzymes Enzymes work by changing the amount of energy required for the reaction to proceed. activation energy  EA Q: What is an enzyme? A: Biological catalyst; speeds up reactions without being consumed (true for organic and inorganic catalysts) Let’s review the potential energy diagram: 1) Relative energy of reactants and products determine endothermic / exothermic 2) Difference between reactants and transition state = activation energy Q: How does an enzyme change the shape of a potential energy diagram? (refer back to the animation) A: Lowers EA so that more reactions can happen.

Reaction Progression Reaction Progession

Enzyme Energy Enzymes lower the activation energy (EA) of reactions. Enzymes lower EA. Energy stored in the reactants and products don’t change. Therefore, free energy of a reaction does not change. (delta G)

enzyme-substrate complex Substrate Binding induced-fit model - enzyme changes shape upon substrate binding enzyme-substrate complex Enzymes are not static.

Substrate Binding Enzymes reduce EA by: bringing R-groups closer to substrate bending bonds to make them easier to break / react bringing two reactants close together providing a microenvironment for reactions

Enzyme Limitations

Enzyme Limitations Enzymes will not make reactions infinitely faster. Only a set number of each type of enzyme in body.

Limitations of Enzymes Enzymes operate at optimal temperature and pH Why? - enzymes increase reaction rate, but only according to how many enzymes are available - enzymes are also limited by temperature and pH - think about bacteria which prefer certain environments (psychrophile vs. thermophiles) Q: What happens in “extreme” conditions? A: Denaturation (remember why we have buffers!!!) - but some enzymes prefer extreme conditions... think pH 2 stomach

Enzyme Limitations Some enzymes require non-protein molecules to work properly. cofactors – inorganic molecules (e.g. iron in haemoglobin) coenzymes – organic molecules (NAD+) An apoenzyme is an enzyme that requires a factor for function, but the factor is missing. Enzymes don’t always act alone.

Enzyme Inhibition Sometimes enzymes are able to bind other molecules which are not the correct substrate. competitive inhibitor – binds to the same active site as the substrate noncompetitive inhibitor – binds to an alternate site on the enzyme to keep it in an inactive form (no longer has affinity for substrate) Competitive: estrogen / tamoxifen / BPA example

Enzyme Inhibition

Enzyme Regulation allosteric site – alternative binding site away from the active site often found in enzymes with 4° structure molecules can bind allosteric site to activate or inhibit enzyme activity allosteric activator – molecule binds allosteric site supporting an active enzyme form allosteric inhibitor – molecule binds to allosteric site supporting an inactive enzyme form

Allosteric Sites Note the two enzyme forms. - identify various allosteric sites - note the different shapes between subunits

Feedback Inhibition Enzyme inhibition is a method for cells to regulate metabolic pathways. Often, products at the end of a series of reactions will act as an allosteric inhibitor to shut the process down. A, B, C and D are molecules along a metabolic pathway. E1, E2 and E3 are enzymes required for this metabolic pathway. D is an allosteric inhibitor of E1.

Homework Leave room in your notes to summarize the Enzyme Limitations section.