When we were kids, life was simpler. All that purrs and meows is a cat. Now that we are 20, “pussy” can mean different things. Concepts develop, yes, but in science there is something you could laugh about when you think hard how your brain perceived lessons back then and how you’d do now.
In this short article, I wanted to point out how taking up an MS degree made me realize how my brain fully comprehended the lock-and-key concept through the ages.
P.S. This is based on the Philippine Education System, and how I perceived things on my own.
High School
A cell is the basic unit of life. Put together, they form a tissue, then tissues with similar functions become an organ, then organs into systems.
“Mitochondria is the powerhouse of the cell.”
I can’t remember encountering lock-and-key concept in HS. When I look through the medicine cabinet and see these tablets, I do not know what they are for unless told by the doctor or my parents. I have zero idea how drugs work when they enter the body. I’m a dummy, alright.
College (Pharmacy)
I entered college to be a pharmacist. I wanted to acquaint myself with the stuff in our first aid kit then eventually make new ones: I wanted to do research.
So it’s in college when I finally encountered Lock-and-Key concept. It was simple at first: you take two different shapes…one is bigger than the other, and the smaller one must fit into the big one like a jigsaw puzzle.
If they fit together, just like a key fits into a lock, a “complex” (or let’s just say a connection of two parts) will be formed, bringing about a change or reaction in the body. This lock is a receptor, while the key is a drug or any substance in the body. A cell can have one or more than two kinds of receptors on its surface or even inside.
When you take an anti-pain tablet, it breaks down into pieces, dissolves into a solution, and some of these particles are drug molecules that eventually find their way to lodge into these locks. We used to draw these drug molecules as a small circle, and the receptor as a bigger circle with a small bite in it — pretty convenient for the small circle to fit into huh?
With the right concentration and enough time, boom! Your headache is gone!
But this is college. Nothing is simple. So you have pharmacology and anatomy-physiology that will tell you which cells and which receptors are responsible for body functions. Physiological pain can be caused by several reasons, and for each reason, there is a drug that can solve it. But not all diseases have cure, okay?
Now, let’s talk about receptors because this is the meat of my article. Receptors are actually protein. They are made up of several amino acids and there are 21 amino acids. Long story short: different sequences of amino acids will code for different proteins. Here is a drawing of how we can form a receptor:
By this time, one can see how linear amino acids can form a 3D shape of the receptor. In our pharmaceutics class, we are taught that receptors can be either activated or blocked (we can also use the term inhibited) by substances already produced by and present in the body or by substances that we take. If we activate the receptor, we promote whatever effect it has; if we block it, it will no longer do what it tends to do.
Let’s say we have a receptor that when activated can make your blood vessels constrict (like your angiotensin II receptors) therefore raising your blood pressure. Attaching to it a drug that would inhibit it will also help you manage your hypertension.
All you gotta do is look for a substance that will fit properly in that magical lock and you have yourself a cure! Or so I thought.
Graduate School
I’m lucky to have re-experienced this lock-and-key concept in a more detailed way: the drug-receptor interaction is literally at a molecular level — I made a video on molecular docking using a computer software (link: https://youtu.be/Y3AXrQRArWg).
A molecule does not have to be a perfect fit at all since both our ligands (i.e. drug) and proteins can be flexible. The “hole” in the receptor is also more than just a small bite — it is like a cave with multiple chambers and these chambers can house different substances, not only one. Plus, the receptor itself can have several caves in it and each of this cave can be activated or blocked to produce different effects, and more so, can be simultaneously triggered to have a combined effect!
To make it more complicated, these “pockets” can also contain water molecules, ions, and other stuff. Some receptors need more than one drug molecule or ions in order to actually “move” and cause a change.
And while we are busy thinking about how “size and shape” will spell the success of fitting a drug into a receptor thereby putting it to work or retirement, we also need to take into account that not all that fits will actually stay inside.
So in reality, even if they are like awesome contortionists — the “joints” of a drug will rotate and bend at different angles, and the amino acids of the protein will do the same until they eclipse — they need to find a good position…and to stay in that position, compatible and stable intermolecular connections between the drug’s and receptor’s atoms must be present. This means that their atoms should hold each other’s hands, and not kick each other’s faces.
What happens if they don’t achieve that? Simple. The receptor will just vomit out the drug like a kid who doesn’t like broccoli.
As long as this lovely connection is present, the receptor will keep on being activated or blocked. But there will come a time that that drug will be metabolized by our body, broken into fragments of what was once a key, and once destroyed, the receptor is free again, resting.
And that should be the start of your next dose.
All of this is still an oversimplication, of course.
Ah yes, being a knowledgeable (and equally stressed) adult makes you realize childhood is awesome. Afterall, when we were kids, life was simpler. All that purrs and meows is a cat. Now that we’re going into 30s, “pussy” can mean different things. It can be the lock, and the key — well I hope you’re old enough to figure it out.
