Enzyme Basics

What is an Enzyme?

An enzyme is a catalyst. Which means enzymes speed up reactions. They make spontaneous but slow reactions possible in a timely fashion. This means that your lunch can be converted to energy before you die of old age.

Enzymes accomplish this by lowering the energy barrier of whatever chemical reaction they catalyze. It is important to note that they can’t change where a reaction starts and where that reaction ends only how fast it gets there. For example, non-spontaneous reactions will still require energy input to occur.

I like to think of it this way. Enzymes are like a speed booster in a car. They can make the car go faster, but if the car is out of gas the speed booster doesn’t do anything. The same is true here. If the reaction isn’t spontaneous or given enough energy to occur the enzyme can’t make the reaction faster. In chemistry terms, this means that enzymes change the kinetics of reactions (rate, collisions, etc.), but not their thermodynamic properties (Gibbs free energy, entropy, enthalpy, etc.)

This leads to an important and frequently tested idea. The intersection between enzymes and equilibrium. Since equilibrium is a thermodynamic property enzymes don’t change the equilibrium concentrations of reactions. Why though? Aren’t they making the reaction faster? Shouldn’t we end up with more product then? Although this seems intuitive enzymes affect both the forward and reverse reactions.

Think about a treadmill. You can increase the speed but so long as you start running faster you don’t go anywhere. Equilibrium is the same!

So in addition to making the forward reaction faster, they also make the reverse reaction faster. Ultimately this balances out and the forward and reverse reactions increase by the same amount. Thus our reaction is stuck at the same equilibrium as before.

How Do They Work?

Now that we have a general idea of what an enzyme is let’s dive into how they work in more detail. I already mentioned that enzymes reduce the energy barrier of reactions, but how? Here I am talking about lowering the activation energy of a reaction or the energy hump a reaction needs to reach to occur.

With chemistry, the higher in energy something is the more unstable it is. The more unstable it is the less likely a chemical compound will move towards that state. Enzymes help by stabilizing the high energy portions of chemical reactions. At these points in time, chemical species exist in “weird” transition states that are particularly unstable. Therefore we can also describe enzymes as transition state stabilizers.

Enzymes accomplish this through a multitude of different mechanisms. They might neutralize an unstable charge or form a temporary covalent bond to stabilize the molecule.

Additionally, enzymes can help catalyze reactions by placing reactants close to one another or in the proper orientation increasing the likelihood a reaction will occur. They can also donate or accept protons to reactants and change their charges. This can enhance the nucleophilicity of an atom or make something a better leaving group. Regardless of how they speed up a reaction, they are also regenerated in the process.

For example, an aspartyl protease might donate an H+ ion to a reactant or intermediate and by the end of the reaction regain it returning the enzyme back to its original state.

Big Picture

So far we have learned about the small details of enzyme catalysis, but what does this look like from a bigger picture perspective. Enzymes have pockets called active sites in them that bind to specific molecules called substrates. When these molecules bind the enzyme usually undergoes a shape change called a conformational change that catalyzes the reaction. While the enzyme is associated with its substrate or substrates the whole structure is referred to as the enzyme-substrate complex.

Once the enzyme has finished catalyzing the reaction it spits out the product and looks for another substrate molecule and begin the catalysis process over again.

Lock and Key

Enzymes are really specific though. So each one will only bind a single substrate or a small group of structurally similar substrates. Originally scientists thought that the high degree of specificity was due to substrates acting like a key that fits a specific lock. This theory appropriately named the lock and key theory suggested that in order for an enzyme to bind to a substrate it must be an exact match for the binding site.

Induced Fit

This was problematic as many enzymes can catalyze reactions with similar but slightly different substrates. This lead scientists to adopt the newer and more accepted induced-fit model of enzyme catalysis. In this model, the active site of an enzyme and the substrate have similar but not identical shapes. This allows them to interact however only the correct substrates will interact in the proper way and induce a change in the enzyme and substrate shape. At this point in time, the enzyme and the substrate become a perfect fit for one another and the enzyme carries out catalysis.

I like to imagine the induced fit model as a door with a keycode. Anyone can come up and start punching in numbers, but only those with the proper code will be able to open the door. In the same way, only substrates with the right shape and enzyme-substrate interactions will undergo catalysis.

Order Matters Sometimes

While many enzymes only require a single substrate molecule other may require multiple substrate molecules based on the reactions they catalyze. In some cases these substrates need to bind in a specific order or the next substrate molecule can only bind once the last one has left.

If the substrates need to bind in a specific order enzyme is said to have an ordered mechanism. Examples of ordered enzymes include DNA polymerase. In this case, the DNA template needs to bind before the free-floating nucleotides do otherwise DNA can’t be used as a template. In contrast, random order enzymes allow the substrates to bind in whatever order they please.

Lastly, ping-pong enzymes catalyze a reaction in series. So once substrate A is bound and converted into product A, substrate B can then bind and be converted into product B. Here two substrate molecules never inhabit the active site at the same time but enter it sequentially.

Cofactors and Coenzymes

Enzymes aren’t always able to catalyze reactions all by themselves. Sometimes they need help from other molecules called cofactors and coenzymes. These “helpers” convert an inactive apoenzyme into its active form called a holoenzyme. Both molecules attach to enzymes with varying strength ranging from weak noncovalent interaction to strong covalent ones. When either a coenzyme or a cofactor is tightly bound to its enzyme it is referred to as a prosthetic group. What’s the difference between the two then?

Cofactors are inorganic molecules such as metal ions while coenzymes are organic ones such as NAD+, FAD+, and coenzyme A. So carbonic anhydrase which uses a Zinc prosthetic group has a cofactor while lactate dehydrogenase which catalyzes a redox reaction with the help of NADH needs a coenzyme to function.