If you were to look at a diagram of all of the enzyme-catalyzed reactions in a cell, the complexity of the map and the spider web-like qualities of the pathways would be enough to make your head spin more than the Mad Tea Party teacups at Disneyland. Yet, each of your cells keeps track of every single one of these reactions.
Even more amazingly, each of these reactions is carefully regulated. Since many enzyme reactions are limited by the interaction of the substrate with enzymes through diffusion, the enzymes can increase the efficiency of their biochemical pathways if enzymes from the same pathway spatially group together. Large, multi-enzyme complexes can be found during many cellular processes. Keep an eye out for them as you study DNA replication and protein synthesis in the weeks to come.
The cell can control enzymatic reactions in many other ways as well. Cells can regulate how much enzyme is produced, or even target an enzyme for destruction. In another scenario, a biological regulator, in the form of a molecule, may bind to an enzyme near its active site. This molecule can affect the ability of the enzyme to catalyze a desired reaction by either inhibiting or stimulating catalysis. This regulatory molecule may also bind positionally farther away from the active site on the enzyme and still regulate its activity. Take that.
During feedback inhibition, an enzyme that does its job early on in a biological pathway is bound and inhibited by a product generated much later in the pathway. Feedback inhibition is a nifty mechanism for the cell; when a lot of product has been generated, the cell can then slow down or turn off the generation of the product. This regulation is called noncompetitive regulation because the inhibitor binds to a different site than the substrate yet still regulates its activity. On the other hand, in competitive inhibition, an inhibitor competes with the substrate for binding to an enzyme’s active site. Competitive inhibition can be compared to you duking it out with your little brother over the last Double-Stuf Oreo in the package. You grabbing it prevents him from grabbing it, and vice versa.
Many protein-based enzymes also consist of small molecules or metals called coenzymes. Our bodies cannot synthesize many of these coenzymes, and therefore, we must consume them as a part of our diet, or as supplemental vitamins. Flintstones Chewables, here we come. Coenzymes bind at or near an enzyme’s active site and assist in catalysis. Coenzymes provide another way for the cell to regulate its enzymatic activity.
In the unit on biomolecules, we learned that proteins (not just enzymes) are the worker bees of the cell. What's more, different proteins have different three-dimensional, or 3D, structures that determine their functions. This may shock you, but when it comes to determining a protein’s structure, thermodynamics plays a big role.
As a protein's polypeptide chain is synthesized (read: made), it immediately begins folding into a compact structure. During folding in water-based solutions, proteins tend to bury their hydrophobic, or water-fearing, amino acids on the inside of the structure, and interactions form between different portions of the polypeptide chain.
Why might a protein want to hide its hydrophobic amino acids? If you said, "because the cell is mostly water, Shmoop," you've just won a trip to Hawaii!* Hydrophobic amino acids like water about as much as a cat does. When it comes to thermodynamics, a protein is all about keeping its "paws" out of water. A protein's structure can also be affected by its interactions with other proteins and cofactors that bind to it.
Regardless, we always know this much: a correctly folded protein has found the lowest energy conformation possible for its structure.
When a protein has lost its highly folded, low-energy conformation, we call it a denatured protein. Certain solvents, or liquids that like to dissolve other molecules, like those with wacky pHs or high salt concentrations, and high temperature will successfully denature a protein. These conditions interfere with the protein’s intramolecular interactions, or interactions between different parts of the same protein molecule, which causes it to unfold.
Sometimes, a protein can refold on its own once the denaturing conditions are removed, a process called…renaturing. Most of the time, though, proteins need the help of other proteins, called chaperones, to fold, or refold, after denaturation. (Side note: You may remember the word "chaperonins" from another unit. Chaperonins are a specific type of chaperone. You're welcome.) Chaperones work by binding to the partially folded protein and encouraging it to take on the structure that is the most energetically favorable. It’s helpful to think of protein folding in terms of an energy diagram. A correctly folded protein will remain in the shape that allowed it to reach its lowest point of energy on the energy curve.
One thing that is blatantly apparent from looking at this energy curve is that the data is jaggedy and fairly ugly. Wait, no. One thing that you may suspect after looking at this energy curve is that a protein can easily get stuck in one of many energy "valleys" on the way to its lowest energy state. These partially folded intermediates, called transition states, can be extremely stable little pockets. If we wanted to get morbid on you, we would compare these pockets to those nasty tree wells you need watch out for when you ski.
Fortunately, it's the role of a chaperone to guide the protein through these energy valleys, helping it along to its lowest energy state. When you look at a protein whose amino acid sequence has changed a lot during evolution, the structure of that protein can remain surprisingly the same. Proteins like ATPase can have "family members," or other proteins that share the same basic structure, which in this case, is the hexokinase family. Even evolution itself is constrained by thermodynamics. A protein’s amino acid sequence may change over time, for various reasons that we won't get into right now, but it must still fold into its lowest obtainable energy conformation when all is said and done.
The million-dollar question at this point is: What happens if a protein doesn’t fold correctly? The answer is that normally, the cell degrades, or destroys, improperly folded proteins. Sometimes, though, improperly folded proteins can escape the cell’s quality control. This tends to have less than optimal consequences.
For instance, a protein that has incorrectly left its hydrophobic amino acids exposed is not just indecent and a waste of space.; it can actually be hazardous to the cell! Exposed hydrophobic protein regions can cause proteins to aggregate (clump together), become undissolved, and fall out of solution. Neurons, or your brain cells, are particularly sensitive to protein aggregation. The sad reality is that many neurodegenerative diseases such as mad cow disease and Alzheimer’s disease are caused by the aggregation of improperly folded proteins.
Proteins are not the only molecules that crave the lowest energy state for biological happiness; biological structures do as well. Plasma membranes are biological structures composed of lipids (see the Biomolecules unit for a refresher) that form the outer barrier of cells. A plasma membrane can be defined as having both hydrophobic, or water-fearing, and hydrophilic, or water-loving, parts to its structure. Plasma membranes contain phospholipid bilayers (phospholipid is often shortened to "lipid") like the one shown below. Given what you know about thermodynamics, where do you think that the hydrophobic parts of the lipids are located in this picture?
Right… the hydrophobic and hydrophilic parts are labeled. We forgot about that.
Just like the "burying" of hydrophobic residues in proteins, the hydrophobic regions of plasma membranes assemble together so that they are not exposed to the aqueous, or water-based, environment of the cell. Unlike the hydrophilic regions, or "heads," the hydrophobic regions, or "tails," of the lipids cannot interact with water molecules because they are uncharged and nonpolar. Lipid bilayers form spontaneously to shelter their hydrophobic regions as well as to promote the interactions of the hydrophilic regions with water. Amazingly, everyone wins. Especially the cell.
If we think about the thermodynamics of plasma membranes a little more, we can ask another question. What shape do you suppose is the most energetically favorable form for the lipid bilayer to take on? If the lipid bilayer formed just a flat sheet, the ends of the sheet would be exposed to water. That's a no-go. The only way that a phospholipid bilayer could completely shield itself from water is to form a sealed compartment, where the inner hydrophobic core of the lipids is shielded from the surrounding water. Tada! We find that a plasma membrane that encapsulates the whole cell is formed through a trio of thermodynamics, structure, and function.
*Trip to Hawaii not guaranteed.
Despite their common roles in catalyzing biochemical reactions, the diversity of enzymes is massive and daunting. In fact, not all enzymes are even proteins! Some of the "oldest" enzymes around are thought to be RNA enzymes, called ribozymes. (RNA is a nucleic acid called ribonucleic acid. Refresh your memory in the Biomolecules unit.) While RNA is often thought of as a messenger and an intermediate between DNA and proteins, scientists now believe that early in the history of Life, RNA played a much more central role.
Scientists discuss the possibility of an "RNA world" where neither DNA nor proteins existed. In this scenario, RNA molecules acted both as storage of genetic material and as enzymes catalyzing important biological reactions. According to this hypothesis, fittingly called the RNA world hypothesis (scientists are so creative), only later on in evolution did DNA and proteins predominantly take over these roles.
Even in organisms today, ribozymes play critical roles in the cell. While the ribosome consists of many proteins, it is the ribosomal RNA in the large subunit that catalyzes the joining of amino acids in the synthesis of proteins. You’ll learn a lot more about ribosomal "RNAs" later, but right now, you can appreciate the fact that RNA can take on complicated structures just like proteins can, and can catalyze important biological reactions to boot. Pretty good, RNA, pretty, pretty, pretty good.
Even if you only focus on protein enzymes, the diversity of the reactions catalyzed by these enzymes is mind-mushing. Take digestion as an example. You know the saying, "you are what you eat?" While it’s true that our bodies rely on food to keep our cells running and to create new cells, it doesn’t mean that if we eat enough Domino's pizza, we’ll turn into a ExtravaganZZa Feast pizza of a different sort. You can thank enzymes for that. Go on; thank them. We'll wait. Welcome back. Enzymes in your digestive tract break down what you eat into useful biological building blocks to keep you alive and kicking.
Now that we mention it, enzymes in your digestive tract determine what nutritional benefits you get from what you eat. The rather shocking part about this is that these enzymes often are not found within cells of your body. That's right; you read us right. Instead, specialized bacteria in your gut determine what your body can or cannot digest. Not all humans have the same bacteria, either.
For example, a special microbe called Bacteroides plebeius is found predominantly in the digestive tract of people of Japan, and it contains enzymes that help them digest seaweed. The diversity of microbes, and the enzymes that they contain, have allowed termites to use that super tasty wood as a food source.