Heat speeds up a rxn but too high of temperature will kill cells and denature (unravel the conformation of) enzymes.

Enzymes speed up rxns by lowering the AE barrier so that the transition state is within reach.  Enzymes cannot make an exergonic rxn endogonic or vice versa.

Transition State is the unstable point where molecules have absorbed all the AE that they can before decomposing.  Then the free E is released.

Active sites are usually formed by a few of the enzyme's amino acids; the rest of the protein is there as infrastructure (support) to maintain the conformation of the active site; is where the substrate (molecule being catalyzed in a rxn) binds to the enzyme

Induced fit is when the substrate is held in place by weak H bonds and ionic bonds to the side chains of the enzyme's amino acid monomers;  this attachment changes the configuration on bonds on the enzyme causing it to "envelop" the substrate (an induced fit)

Mechanisms that enzymes use to lower AE include the following:

1. induced fit
   1. It may stretch and bend the substrate's bonds.
   2. Since AE is proportional to the difficulty of breaking bonds, distortion reduces the amount of thermal E (heat) needed to get to the transition state.
2. microenvironments (eg pocket of low pH)
   1. If side chains (R groups) are acidic, the active site has lower pH than the cell;  thus, because it's acidic H⁺ transfers more easily for hydrolysis of bonds.
3. direct participation of the active site
   1. The active site's R groups covalently bond to the substrate(s).

Saturated Enzymes

If all enzymes are busy with substrates; thus adding substrate won't raise the rate of rxn.  You need to add more enzyme proteins to the substrate.

The Chemical and Physical Environment affects Enzyme Activity

1. Temperature, Changes in
   
   High temperatures raise the thermal agitation of not only the substrate's bonds but also the protein's.  Too much thermal agitation disrupts H bonds, ionic bonds, and other tertiary structures that maintain conformation.
2. pH, Changes in
   

Cofactors and Inhibitors

Cofactors are nonprotein inorganic helpers for catalytic activity.
     e.g. zinc, iron, copper

Coenzymes are nonprotein organic helpers for catalytic activity.
     e.g., vitamins
     NOTE:  most vitamins are coenzymes themselves or raw materials for coenzymes

Inhibitors may or may not be reversed once activated depending on the type of bond used. If a covalent bond is used, it is often irreversible.  If one of the various weak bonds is used, then it is reversible. There are 2 types of inhibitors:  competitive and noncompetitive. A competitive inhibitor mimics the substrate and "competes" with it for admission to the active site, blocking the substrate from entering.  If reversible, this can be overcome by adding more substrate; so that when an enzyme does free up the normal substrate has a higher chance of being admitted.  A noncompetitive inhibitor binds to a part of the enzyme away from the active site; thus changing the shape of the enzyme and making the active site unreceptive to the substrate, or making the enzyme less effective at catalyzing the reation.

e.g.  DDT and parathion inhibit receptor enzymes in the nervous system.  Penicillin (competitive inhibition) blocks the active site of the enzyme that bacteria use to make their cell walls.

Allosteric Regulation is a mechanism of noncompetitive inhibition.   Molecules that regulate enzyme activity bind to the/an allosteric site. An allosteric site is a location on the protein away from the active site that influences the active site.  Most enzymes that have this have 2 or more polypeptide chains.  Each chain has an active site.  Allosteric sites are usually where the polypeptides join.  The quaternary structure of the enzyme alternates between active (capable of binding to the substrate) and inactive (incapable of enzymatic activity).  When an activator bonds with the active form's allosteric region, it stabilizes the active form of the enzyme. When an inhibitor binds to the same region, it maintains the inactive form of the enzyme.

Cooperativity:  "One for all and all for one!"
Cooperativity is the introduction of 1 substrate in an active area of a quaternary enzyme stimulates ALL active sites (each active site per subunit) to remain favorable to substrate molecules.  In other terms, having one substrate in an active site prevents any inhibition of an enzyme (having allosteric sites) in all regions.

Feedback Inhibition:  another method of regulating metabolism.
In feedback inhibition, a metabolic pathway is turned off by its end product being an inhibitor for the enzyme that catalyzes the first step on the metabolic pathway.

How structural order influences metabolism:

1. "Teams" of enzymes for the steps in a specific metabolic pathway are grouped together into multi-enzyme complexes separated from other "teams" by membranes.
   e.g., peroxisomes
2. Some enzymes are built into the membrane; thus have a fixed location.
   e.g., various enzymes for cellular respiration are in the interior foldings (cristae) of mitochondria