Muscle Maintenance: The Cost of Strength
One good example of protein turnover in action is muscle. When someone lifts weights, the body responds by adding more functional proteins to the muscle. This increases its strength (I will discuss the full mechanism in a future post). This is what adds mass and volume to a bodybuilder’s physique. However, these proteins are both fragile and energetically costly. As a result, everybody’s muscular system exhibits protein turnover on a massive scale.
Our muscular system is constantly undergoing remodeling. This means that at any given time, our muscle fibers are constantly braking down and building up their proteins.
How Muscles Remodel Themselves
Muscle is built up when the rate of synthesis is greater than that of muscle breakdown (hypertrophy). The opposite also applies; if the rate of breakdown exceeds that of synthesis, you lose muscle mass (atrophy). The key to alter these rates is to provide a stimulus that signals to the body to favor one state more.
If someone is regularly lifting weights, it is easy to imagine that their body will add muscle mass as an adaptation to the stressful environment: the cells simply “believe” that more strength is needed for the organism to survive. This is basic homeostasis: the body tries to compensate for uncomfortable external stresses by adapting physical resistance. This is especially evident in diabetes.
In contrast, if a person lives a sedentary life, the cells have no stimulus to build muscle. In their eyes, the muscle mass is just a waste of energy to maintain: the protein functions of muscle are not needed. The body will break down the damaged tissue and consume it for energy.
We can carry this analogy over to almost every protein. In fact, our cells themselves regenerate so often that we are almost entirely new every 10 years. Of course, this is not true for certain cells such as the lenses of your eyes and your brain, which remain with you for most, if not all, of life. However, your skin regenerates entirely every month and your blood about every 6 months. The point is that proteins, although essential, consume a large portion of energy generated by cells.
The Consequences when Protein Functions are Altered
As you can imagine, relying on such complex pieces of machinery comes at a risk of dysfunction. While some change in protein functions can result in an improved organism (natural selection), the vast majority of changes are detrimental to cellular chemistry. This is because making changes in such a complicated system has a high chance of disrupting the entire system. This is like someone undergoing brain surgery except that the end result is dictated by chance (we will discuss the pathway of information processing in cells later).
Since misfolded proteins can wreak havoc on the cellular environment, many organisms invest a lot of energy and resources in developing pathways to destroy rogue proteins. Essentially, cells mark proteins that are forming too slowly (or seem too reactive) for destruction.
Collateral Damage: Protein Housekeeping
Although these systems are effective in removing bad proteins, they also readily break down good proteins. This is because the system involved in marking proteins is fast acting and does not discriminate between proteins. If a cell is trying to make a healthy protein but it happens to be in the vicinity of one of these “marking enzymes”, then the enzyme will mark the protein for breakdown. In fact, up to 30% of good proteins are digested before they completely form.
Think about what this means! An organism that exists because of its efficient use of energy and resources readily throws away one third of its most costly product just to remove a few bad eggs. This implies that mistakes in proteins must be disastrous if they are not removed.
Protein Functions and Computing: Fatal Mistakes due to Improper Function
Lets move to two examples that create a good analogy for this phenomenon: one biological and one technical.
The Bit Flip
Lets begin with an example in computing, specifically in rocket hardware. To understand the analogy, it is important to define what a computer processor is: essentially, a processor is a calculator that analyzes inputs to give you a desired result. In your computer, processors are responsible for everything you do, from loading a web-page to typing on your keyboard. However, in space, the job of a processor is much harder.
The reason for the difficulty is radiation. When a high energy particle from the sun hits a data stream, it causes a bit flip, essentially changing a 1 to a 0 or a 0 to a 1. Typically, this results in a single fixable error. However, when the particle causes a bit flip in the processor (calculator), the numbers involved in the calculations are affected. Thus, entire outputs are incorrect, essentially producing corrupted numbers forever. As you can imagine, incorrect calculations in a rocket can have disastrous consequences. Therefore, companies keep redundant backups or radiation resistant processors for security.
The Prion
In the above example, the processor is essentially the protein: a misfolded protein has the ability to create products that can harm the cell due to its reactivity. Now, let’s look at the biological equivalent: prion diseases. In prion diseases, the defense system fails to destroy a bad protein (prion) and it escapes into the cell. Alone, most prions are harmless, causing mild interference in cell processes due to impaired normal protein functions. However, prions have a unique ability to turn good variants of the same protein into the prion variant by “bumping into” them.
This causes an exponential “infection like” spread of prions. At this point, the organism has lost a significant amount of essential protein. The prion proteins swarm the cells. This results in a system wide disability. The most well known example of prions is mad cow disease which manifests in the nervous system of cattle. In addition, human consumption of contaminated meat can transmit this prion into human bodies, first multiplying in various organs and then inducing Creutzfeldt-Jacob disease, destroying human nervous tissue in the same way. The disease literally pokes holes in your brain until you die. It has no cure. .
Conclusion
Complex life on Earth is entirely reliant on proteins. Without these robotic machines, it would be impossible for organisms to make anything from fingernails to blood. Nature makes and sustains our bodies by using an enormous variety of proteins. Each of these machines is essential to the function of a specific system. Differences in these proteins are the reason the evolution of humans is so different from that of plants, for example.
Life uses proteins to build machines capable of using environmental resources to regenerate. However, this raises an even bigger question: if proteins are made in order to create cells, what stores the information used to create them? In other words, what molecule is the original replicator that started life on Earth? We will answer this question in the next post: DNA.