By Robert Hazen, George Mason University
One of the great exciting things in science these days is that we can design drugs to perform certain functions. It has been made possible as we are beginning to understand how enzymes work. So how do enzymes really work? Read on to know more.
Enzymes
Most proteins serve highly specialized biological functions as chemical enzymes, that is, they control reactions in biological systems. Much of the history of biochemistry, since the early 19th century, has been trying to discover what these enzymes do—what the chemicals are and how they work.
A catalyst is a chemical that speeds up a chemical reaction, without itself being changed. Our cars, for example, have a catalytic converter. The catalytic converter doesn’t change over the course of our driving, but it does help reduce the harmful emissions from our automobiles. Enzymes do the exact same thing.
We can think of an enzyme as a kind of chemical machine, a machine that performs a specific function without itself being changed. We use this kind of machine all the time; a typical example is a stapler. Another kind of machine is a staple remover. In both these cases, form follows function. The function of these objects is perfectly designed to apply or remove staples, without themselves being changed.
Synthesis of Enzymes
Synthetic enzymes are just like staplers. They have grooves and furrows on their surface called active sites. Those grooves and furrows match exactly to the shape of two or more molecules that may come together, and that enzyme essentially staples the two pieces together. There are also digestive enzymes, which act just like a staple remover.
In other words, we have a molecule that fits into the groove of this enzyme; the enzyme acts to split apart two pieces that otherwise would be together. So again, we have form following function; we have essentially a tiny molecular machine that either synthesizes things or breaks them apart.
Importance of Molecular Shape
The behavior of enzymes illustrates why molecular shape is so critical to modern computer-aided drug design. Many drugs work by binding to the active site of an enzyme, thus blocking its function.
One type of enzyme, for example, synthesizes neurotransmitters, and these help convey nerve impulses to the brain, especially the nerve impulses that we sense as pain. When one takes an aspirin, they’re blocking an active site on an enzyme that produces these neurotransmitters. If we don’t produce as many neurotransmitters, we don’t feel as many pain impulses. Valium and alcohol also have a shape that blocks sites specifically involved in transmitting nerve impulses, and that’s why they dull the sense of pain. All sorts of designer drugs adopt this strategy.
When we try to determine the function of an enzyme, we determine the shape of its active site; we design a drug that fits into that active site and blocks the action of the enzyme. If we tie up the enzyme by filling up its active sites, it can’t perform the normal function. Of course, this requires knowing the exact shape of that active site, which involves knowing the structure of the protein.
This is a transcript from the video series The Joy of Science. Watch it now, on Wondrium.
Proteins in Our Diet
Proteins play a crucial role in cellular functions because of which we have to have an adequate supply of protein in our diet. That basically means we have to have an adequate supply of the basic amino acids, the building blocks of proteins.
Not all these amino acids are manufactured in the human body. Human adults synthesize 12 of those 20 amino acids; but the remaining 8, the 8 amino acids that our human bodies cannot produce, are called the essential amino acids. One has to eat those in their diet. For example, humans require a steady source of the amino acid lysine, of leucine, of tryptophan, all of which are available as dietary supplements.
Differing Protein Content
Food varies quite considerably in its protein content. Bananas have only 1 percent protein; some kinds of beans have 30 percent protein. Many dairy products also have very high levels of proteins. But not all protein-rich foods have the essential amino acids that we need.
As one might expect, foods that match the human needs, those 8, are more valued, and they are said to be high-quality proteins. Foods that don’t match the 8 essential amino acids that we need are called low-quality proteins. Quite logically, animals generally have a higher ratio of high-quality proteins; so meats and animal products, dairy products, tend to be much higher in these high-quality proteins, since animals are much more closely related to us, chemically and genetically.
Traditional Vegetarian Diets
Plants often have low-quality proteins, but it’s intriguing that combinations of different kinds of plants can provide a very complete and adequate diet. A combination of grains and beans, for example, gives you a complete balance of those essential amino acids. It turns out that people on vegetarian diets have to be very careful about planning their diet accordingly, to make sure they don’t have protein deficiencies.
Many of the traditional vegetarian diets do this automatically, because they combine different types of vegetable items. For example, in Asia, it’s common to see tofu and rice in the diet; that gives us all the essential amino acids. Similarly, in Africa, rice and nuts is a common diet. In Mexico, tortillas and beans also provide that complete list of essential amino acids.
Common Questions about Synthesis of Enzymes and Drug Design
Synthetic enzymes are just like staplers. They have grooves and furrows on their surface called active sites. Those grooves and furrows match exactly to the shape of two or more molecules that may come together, and that enzyme essentially staples the two pieces together.
The behavior of enzymes illustrates why molecular shape is so critical to modern computer-aided drug design. Many drugs work by binding to the active site of an enzyme, thus blocking its function.
Proteins play a crucial role in cellular functions because of which we have to have an adequate supply of protein in our diet. That basically means we have to have an adequate supply of the basic amino acids, the building blocks of proteins.
