Biology - Molecules and Cells

 Terms and Concepts 

SECTION 1

CHAPTER 6 - Dynamic Processes

Chemical reactions have arrows that show a direction that is not always the reality - if reactants can react to form products, then sometimes products can convert back to reactants.  As reactions continue and build 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 reactions to run at the same rates both ways.  Some reactions hit an equilibrium point quickly - the equilibrium 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.

The basics of chemical reactions.

Dynamic equilibrium. (Video)

 

Equilibrium demonstration, including the influence of temperature. (Video)

As systems get closer to equilibrium, the reverse rate goes up and the forward rate slows down, a fact that factors into either controlling a reaction or preventing it from slowing.  The progress to equilibrium can be disturbed in several ways.  One common way to keep the reaction going 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 pathway's next step can drive the pathway - the equilibrium does not become a factor until the final product begins to build up.  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 will be limited by the reactant (or enzyme) in shortest supply - this is called a limiting factor, sometimes used as a controlling factor.

Illustration of simple intersecting pathways in hormone production.

An example of a limiting factor. (Video)

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 barriers at high rates of speed.  When particles collide that can interact chemically, you may get a reaction that changes them.  This reaction goes on at a rate, designated k, Q, or V (for velocity) that is affected by the circumstances.  Usually, a test tube full of particles needs a little "boost" to get a significant number of them reacting with each other.  The energy needed to get a sizable reaction going is called activation energy.

Page about the "bump" of activation energy, and how a catalyst can lower it.

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 applied to 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.

A lot more on Q10.

In many reactions, energy is released, as the energy state of the products, the energy still in the system, is lower than that of the reactants.  If enough energy is released that it can 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 often 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 in a way that makes them less stable and more likely to react. 

A discussion of the reaction types.

Discussion of endergonic reactions.

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 parts of the system.  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.

Introduction to the 2nd Law.

How the 2nd Law works in physics.

Another approach to getting reactions going is to 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 or products no longer fit in the active site and are released by the enzyme, which can then grab new substrates.

How catalysts affect activation energy.

Enzymes as catalysts.

A lot about enzymes.

Enzyme activity can be measured with a reaction rate or with a turnover number, the number of substrates an enzyme molecule can process in a second.  Some reactions are sped up many thousands of times by enzymes over what might happen without them.  The chemistry of our cells, 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.

Use of turnover numbers in research. (Article)

Enzyme information.

As substrates are added to a system with a constant amount of enzymes, the overall reaction rate follows a pattern called Michaelis-Menten Kinetics.  Take a look at the graph - you'll 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 - it's less and less likely that an added substrate will find an unoccupied enzyme it can attach to - and the upswing of the reaction rate lessens.  The steep rise curves over to a more-and-more horizontal line.  When the line is completely horizontal, all of the enzyme molecules are busy all the time, no matter how much more substrate is added, and the rate is as fast as it's 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, and it can measure their binding strength or affinity.  An enzyme with a high affinity is very "sticky" for substrates, holding onto them longer.  The enzyme molecules will become occupied more 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 it's 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 (or the enzyme in a lower supply) 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.

Introduction to Michaelis-Menten.

The graph mentioned in the text.

More on Michaelis-Menten.
 

More on the Michaelis Constant.
 

Effects of enzyme concentration.

Acetaminophen pathway.

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 protein's 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 ions 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.

Weird computer voice talking about denaturation. (Video)

Optimum (optimal) 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 won't 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 and the "fit" of active sites as well).   Optimum (optimal) pH peaks when the ionic environment is just right to support an enzyme's 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 changes shape and just stops working.

More on optimum temperature.

More on optimum pH.

Glacier research, including information on ice worms.

Organisms that can survive acidic environments still have "normal" optimum pH.

The graphs associated with enzyme activity may be steep and narrow, broad and flat, asymmetrical, or any variation.  It may be to an organism's advantage to have enzymes with 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. 

Variations in the curves.

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 move 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.  All vitamins are coenzymes, but not all coenzymes are vitamins, and the term is specifically the group that humans can't make.

How a cofactor might work.

Vitamins, minerals, and issues with supplements.

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.  Sometimes enzymes are made in one place but activated elsewhere - many of our digestive enzymes are made in the pancreas but not activated until in the (lining-protected) intestine.  These circumstances require 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 also commonly an effect of toxins;  a great number of poisons affect cell chemistry by changing enzyme molecules in ways that can't be fixed.

There is actually a Journal of Enzyme Inhibition.
 

More on enzyme inhibition.

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.

Direct (competitive)inhibition illustration.

Indirect illustrated.

Direct and allosteric inhibition. (Video)

Allosteric illustrated.

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.

End-product inhibition. (Video)

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.

More on regulatory sites.

Terms and Concepts

In the order they were covered.

   Dynamic Equilibrium  
Limiting Factor - Reactants  
Reaction Rates - k, Q, V  
Activation Energy  
Q10   
Exergonic Reactions  
Endergonic Reactions  
Coupled Reactions  
ATP & Coupled Reactions  
Second Law of Thermodynamics  
Catalysts & Activation Energy  
Enzymes as Catalysts  
Substrates of Enzymes  
Active Sites  
Turnover Number  
Michaelis - Menten Kinetics  
Vmax  
Michaelis Constant - Km  
Affinity  
Limiting Factor - Pathway Enzyme  
Denaturation  
Optimum Temperature  
Optimum pH  
Cofactors
Coenzymes
Vitamins
Inhibition  
Reversible Inhibition  
Irreversible Inhibition  
Toxins as Enzyme Inhibitors  
Direct Enzyme Inhibition  
Competitive Enzyme Inhibition  
Indirect Enzyme Inhibition  
Allosteric Effects  
End Product Inhibition 
Regulatory Sites