CHEMICALS THAT REACT CAN "UNREACT"

Chemical reactions have arrows that show a direction that is not necessarily reality - if reactants can react to form products, then sometimes products can convert back to reactants.  When reactions continue indefinitely, building up products which themselves can change back to reactants, eventually they will hit a point at which reactants and products are reacting back-and-forth at the same rate - reactants become products as often as products become reactants.  This point is called dynamic equilibrium.  The reaction continues to occur, but the amounts of products and reactants no longer change.  Often, for a reaction represented as running just one way, there needs to be huge amounts of product and not much reactant left for the conversions to run at the same rates both ways.  Some reactions hit an equilibrium point quickly - the point is linked to how stable both the reactants and products are.  In some cases, say when a very complex molecule breaks down, there is no reverse reaction, so not every reaction can hit a dynamic equilibrium.  Later, a similar sort of equilibrium will be discussed that involves particles moving through a barrier, and some of the other concepts discussed in this section will apply to those situations as well.

As systems get closer to equilibrium, the forward rate slows down, a fact that can be used to either control a reaction or prevent it from slowing.  The progress to equilibrium can be disturbed in several ways.  One common way is to remove product from the system - if the product can not build up, it can not convert back to reactants easily.  In pathways, the fact that a product becomes a reactant for the pathways next step can drive the pathway - the equilibrium may eventually build up across the entire width of the multi-step process, however.  Reactants can be added as well, to pump up the forward reaction - but if there are multiple reactants, they all need to be added.  In many processes, the reaction is limited by the reactant (or enzyme) in shortest supply - this is called a limiting factor, sometimes used as a controlling factor.

 REACTIONS AND ENERGY

At the atomic level, atoms, ions, and molecules are particles flying through space at high velocities, bouncing off each other and the organized surfaces of solid (if that means anything at the atomic level) barriers at high rates of speed.  When particles collide that can interact in terms of electrons and chemical stability, you may get a reaction that changes them.  This reaction goes on at a rate, designated k, Q, or V (for velocity) and dictated by the circumstances.  In the world of people, a test tube full of particles needs a little "boost" to get enough reactions for it to look to us like somethings going on.  The energy needed to get a sizable reaction going is called activation energy.

Activation energy can be supplied by something that increases the chances of the reaction happening - heat, which speeds up the velocity of the particles, is a common activation energy source.  A common measurement of reactions is the Q₁₀, which is the change a rate undergoes when the temperature is raised 10^o C.  Many reaction rates come close to doubling with this seemingly minor change in temperature.

In many reactions energy is released, as the energy state of the products is much lower than the reactants.  If enough energy is released to provide activation energy for more reactions, the reaction will continue, fueling itself.  This is an exergonic reaction - an example would be a burning piece of paper, a fast oxidation reaction that, once started with enough heat, releases enough heat itself to burn the rest of the available paper.  Many reactions require constant energy input to run - these are endergonic reactions.  In biological systems, reactions are commonly coupled - an exergonic reaction will be used to provide energy to an endergonic one.  Commonly, the exergonic transfer of phosphate groups, usually from Adenosine Triphosphate (ATP), can energize molecules, making them less stable and more likely to react. 

One should remember that, even though the Second Law of Thermodynamics (the Entropy Law) states that ordered systems tend to gradually fall apart, this rule does not apply where available energy can be used to build, sustain, and repair complex molecules.  And even though complex molecules will occasionally break apart by themselves, they are generally repaired or replaced.  Breakdown is an important process in living systems, but it is breakdown of specific molecules at specific times, rigidly controlled.

Another approach to getting reactions going is to somehow reduce the activation energy they require to start - this is done by catalysts, which in biological systems are almost always enzymes.  Enzymes "grab" reactants (called substrates when enzymes are involved) in surface dents called active sites and, in various ways, greatly increase the chances of their reacting, lowering the energy needed to get them to react.  Once reacted, the new product no longer fits and is released by the enzyme, which can then grab new substrates.  

Enzyme activity can be measured with a turnover number, the number of substrates an enzyme molecule processes per second.  Some reactions are sped up many thousands of times by enzymes over what might just happen in solution.  Life as we know it could not proceed without enzymes.  The turnover number is a kind of ideal maximum - it assumes that there are substrates available to be grabbed when products are released, which is not always true.  Some enzyme-catalyzed reactions are kept closer to maximum possible rate by confining them to small spaces within a cell - if the substrates and enzymes are jammed in a small chamber together, it will be easier for them to interact.  This is part of the reason why eukaryote cells have so many specialized chambers inside them.

As substrates are added to a constant amount of enzymes, the overall reaction rate follows a pattern called Michaelis-Menten Kinetics.  Take a look at the graph - youll see that as substrate is added, it quickly gets grabbed by available enzymes and the reaction rate shoots up.  However, as more and more substrate gets added, the enzymes get busier and busier - its less and less likely that an added substrate will find an unoccupied enzyme it can attach to - and the reaction rate stops climbing.  The steep rise curves over to a more-and-more horizontal line.  When the line is completely horizontal, all enzymes are active all the time, no matter how much more substrate is added, and the rate is as fast as its going to get - this is the maximum rate under these circumstances, called Vmax.  Another term, the Michaelis Constant, represented as Km, is set at the substrate concentration for which the rate is half of Vmax.  This becomes a useful way to compare enzymes - it measures their binding strength or affinity.  An enzyme with a high affinity is very "sticky" for substrates, and will become occupied very quickly and hit Vmax quickly with small amounts of substrate.  This can be useful when an enzyme-catalyzed reaction needs to be done constantly in the presence of substrate, but its better done at a relatively slow rate.  In a pathway that depends upon multiple enzymes, as substrates become plentiful the enzyme with the lowest Km may become the limiting factor, a sort of bottleneck in the system - it is this effect, with the buildup of a toxic intermediate molecule, that can make an overdose of acetaminophen deadly, killing the liver cells that are processing it.

FACTORS AFFECTING ENZYME ACTIVITY

Enzymes are large protein molecules held together by hydrogen bonds of various strengths, able to keep their tertiary structure together to varying degrees, depending upon their surroundings.  If the proteins shape changes enough to alter its active site, it will stop working.

Denaturation, the general opening up of the molecule, can happen when hydrogen bonds are disrupted in many places at once.  This can occur when the temperature gets high enough to vibrate the bonds apart, or when charged particles, such as those associated with acids or bases, interfere with bond attractions.  With both of these factors, there are points at which a particular enzyme will be at peak activity - this is called the optimum.

Optimum temperature peaks between temperatures too high for all of the enzymes to be properly configured - and the warmer it gets, the larger fraction of molecules wont be able to work - and low temperatures at which the particles are moving slowly enough to affect rate (it is to be expected that lower temperatures might also affect tertiary structure as well).   Optimum pH peaks when the ionic environment is just right to support an enzymes proper structure.  Different enzymes have different optimums - it makes sense that our optimum temperature is around typical human body temperature, while a fish in Arctic waters should have enzymes with much lower optimum temperatures.  It is thought that we produce fevers in an attempt to disrupt the chemistry of invading organisms, or that some of our immunity proteins have a higher-than-body-temp optimal.  When pollution acidifies lakes and ponds, organisms may die when the pH around them slips away from their optimums.  When pepsin, a protein-digesting enzyme active in the acidic confines of the stomach, reaches the slightly basic environment of the intestines, it just stops working.

The graphs associated with enzyme activity may be steep and narrow, broad and flat, asymmetrical, or any variation.  It may be to an organisms advantage to have a broad range of activity, even if the activity peak is limited a bit.  In organisms active across a broad range of temperatures, there may be two or more enzymes doing the same work in different temperature ranges. 

Enzymes also often work with molecular "partners" that can do some things that enzymes are poor at.  These can be cofactors, commonly mineral ions that help more electrons around (not the same as the minerals that occupy prosthetic groups, which are permanent parts of the active enzymes), and coenzymes, small organic molecules that perform a variety of helpful tasks.  A subset of coenzymes used in human cells have been long available in our food, and we have given up the ability to synthesize them - these are the vitamins.

 CONTROLLING ENZYME ACTIVITY

The jobs done by enzymes in living systems vary from the constant to the every-once-in-a-while.  For enzymes used frequently but not continuously, it makes sense to deactivate them and reactivate them, rather than breaking them down and building new ones later.  This requires a way of switching an enzyme molecule from an active form to an inactive form - a process called inhibition - and being able to put it back in the active form - reversible inhibition.  Irreversible inhibition is a process that happens sometimes to enzymes bound for recycling, but it is commonly an effect of toxins;  a great number of poisons affect cell chemistry by changing enzyme molecules in ways that cant be fixed.

Reversible enzyme inhibition involves molecules that bind to enzymes in one or more domains.  All of these work at cutting off enzyme-substrate binding.  Direct inhibition involves binding in the actual active site, so substrate cannot bind there.  This is also called competitive inhibition, since both substrates, reactant and inhibitor, bind to the same place.  Indirect inhibition (noncompetitive) can involve binding near an active site in a way that prevents substrate from getting to it, or binding to the enzyme and changing its shape or conformation enough to distort the active site.  When binding at one site changes the shape of another site, this is called an allosteric effect, and is a common way for several classes of proteins to work.

In end-product inhibition, the product of a multi-step pathway is able to bind to the first-step enzyme and shut it off.  As product levels rise, enzyme production drops - as products are pulled from enzymes and used, production goes up.

Domains on an enzyme where inhibitors are supposed to attach as part of the regular control systems are called regulatory sites.  Enzymes can have multiple binding sites on their surfaces - for substrates, for structural proteins, for membranes, for inhibitors, for just about anything that they would need to be attached to.

USEFUL LINKS:

A page showing variations of Michaelis-Menten curves with varied inputs.

The 2nd Law of Thermodynamics applied to marital breakups.