Deciphering The Lock And Key Mechanism That Our Body's Cells Abide By.
How can the lock and key mechanism be used to understand how our cells function?
The idea of a lock and key mechanism was borne out of a need for security.
We have valuables to safeguard. We have private issues that we don’t want to make public. We keep them locked up and hidden away.
However, we do have keys to unlock those locks and gain access to our private stashes.
In the same way, a lot of the cells in our body communicate on a lock and key mechanism, which we can collectively term as “cell signalling”.
Our cells have receptors on their surfaces, and specific biochemicals can bind to those receptors to signal them to do something.
For example, our cells possess insulin receptors. Insulin is produced by the beta cells in the pancreas when we consume food, and it then binds to the insulin receptor on the cell to signal the cell to take in glucose from the blood.
In this situation, the presence of insulin unlocks the cell’s ability to take in glucose from the blood. Insulin stays in the insulin receptor for a specific period of time, which we call the residence time. After that period of residence, it dissociates (or it separates itself) from the insulin receptor, and that ends the cell’s activity in taking in glucose.
It is important to note that there can be different keys that can bind onto the lock receptor, much like how a thief can use a safety pin to unlock a car’s or house’s doors to steal valuables from the car or house.
However, even though different things can fit into the lock, only some will be able to truly unlock the biochemical process that is contained within. Others will stay within the lock and prevent a biochemical process from occurring, which is what happens in drug development and discovery.
The “lock” is 3-dimensional and depends on the specific orientation of the biomolecule.
Many molecules are chiral in nature. They have similar chemical compositions, but their structural arrangements are different. For more information on chirality, this Youtube video serves as a good explanation:
Broadly speaking, we can classify simple chiral molecules as levorotatory (L, or rotating a plane of light leftwards) or dextrorotatory (D, or rotating a plane of light rightwards).
A normal chemical synthesis of these molecules results in a racemic mixture (approximately 50–50) of the L and D isomers, which are also known as stereoisomers or enantiomers.
To complicate matters further, these stereoisomers can also be classified as R (rectus) or S (sinister) molecules, which illustrates the configuration of the functional groups on the molecule instead of the direction of light rotation. This is especially more convenient for describing molecules that have more than 1 chiral centre.
Ibuprofen, for example, is marketed as a non-steroidal anti-inflammatory drug. The R-enantiomer is pharmacologically inactive, while the S-enantiomer is the one that inhibits the cyclooxygenase enzymes from proceeding with their pro-inflammatory biochemical pathways.
Therefore, the S enantiomer fits into the cyclooxygenase enzyme lock, while the R doesn’t really do squat with the cyclooxygenase enzymes. The chirality of the molecule also plays a big role in the lock and key mechanism.
So if we were to chemically synthesise ibuprofen, we’d end up with a 50-50 mix of the R- and the S-enantiomers. If we were to take that 50-50 mix and turn it into a tablet, only 50% of it would be pharmacologically active. The other 50%… would just contribute to gastric discomfort without providing pain relief.
The downside of purifying the mixture to obtain a purer S-enantiomer product?
It’s gonna cost more.
Getting the cells to consistently provide signals to each other in a healthy manner is a tall order.
In the first place, most of us are born with next to no signalling issues. One cell produces a biochemical, which then signals another cell to do something. Kind of like when we were playing a game of Chinese whispers as kids.
You know, the game where everyone would stand in a line? The person at the head of the line would create a message and whisper it to the second person. The second person would listen to what the first person said and try to replicate it for the third person.
Oftentimes, the message gets garbled towards the end of the line, especially when there are no control measures involved to ensure that the right message gets passed along. Kids operating with nothing but mischief in their minds (like me) would deliberately mess up the message.
But that’s how our cells function. There is a cascade of signalling events, and when one event goes awry, we’d see the symptom of a disease emerge.
In Type 1 diabetes, for instance, the beta cell population is mistakenly diagnosed by the immune system to be a dangerous invader and is killed off by the immune system.
The surviving beta cells do not have enough insulin production capacity and are underproducing insulin. When there are insufficient keys to unlock all the locks, most cells will end up taking in less glucose than they are supposed to be taking in, leaving the leftover glucose to accumulate in the blood, which leads to diabetes over time.
Because the problem here is an underproduction of insulin, there are 2 ways to go about solving the problem:
Rejig the immune system to not misdiagnose the beta cells as foreign invaders (which is next to impossible).
Introduce constant insulin injections to bump up blood insulin levels (which is a more sane option as compared to Point 1). This is the usual style of managing Type 1 diabetes.
Hence, the Type 1 diabetic would have to be dependent on insulin for life because their insulin production capabilities are reduced. Unfortunately, they have no other way of stopping their immune system from killing off the beta cells indiscriminately.
Some people are born with the issue, and that makes it worse. Because being born with it indicates that the genetic material in their DNA is faulty, and no rectification is possible other than gene therapy/genetic modification, which is on its own a very uncertain technology for humans to be dealing with.
But certain aspects of our lifestyles can help our cells to communicate better.
And that’s why we have this common lifestyle mantra of getting sufficient quality sleep, regular exercise, a proper diet and good stress management.
If we can balance that out, the epigenetics behind how our body operates will be affected in a positive manner:
Your genes play an important role in your health, but so do your behaviors and environment, such as what you eat and how physically active you are. Unlike genetic changes, epigenetic changes are reversible and do not change your DNA sequence, but they can change how your body reads a DNA sequence.
So while one may be born with Type 1 diabetes (which an irreversible change in their DNA sequence), how they live will also affect how their bodies respond in the future. Hence we can never preclude one who is born with Type 1 diabetes from getting Type 2 diabetes as they grow older.
Unfortunately, a lot of these issues start out at the molecular level, and we aren’t really conditioned to notice what is happening at such a small scale. Being aware of these issues would help us to understand how our body can function properly, as well as what we can do to prevent the development of nasty health issues as we age.
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