Orchestrating the Pathways of Life — Redox Signaling Semaphores

These first few posts are helpful to bring our minds into the framework that will allow us to understand what life looks like on the molecular scale, all with the end to help conceptualize what the signaling networks that define life and connect all of the molecular players might look like on the molecular scale inside our body. On the molecular scale, everything is immense; there are a trillion billion water molecules in just one small drop of water, almost an unfathomable amount; in reality even the smallest drop of water contains a vast ocean of water molecules, stretching off into infinity in all directions in the molecular perspective. Even a single cell in this perspective, contains an enormous pool of molecules surrounded by an undulating membrane containing “windows” and “doors” (receptors) that allow molecules to pass through from the outside to the inside of our cells. Each cell can be thought of as a submerged “house” that protects the processes of life taking place inside. The molecular materials and supplies that the cell needs comes in through selective “windows” and “doors” (oxygen, nutrients, building materials, etc.); very few molecules can “seep in” through the cracks.
The pushing and pulling action of the constantly jostling sea of water molecules mark the pathways that molecules follow as they navigate through this ocean of water molecules inside your body. As molecules travel through this sea of water molecules, it can be somewhat like watching a huge “pinball” game. The traveling molecules will be bounced, pushed and pulled along through an array of “bumpers” and “magnets” until they finally arrive at their destination. Every once in a while, there will be a “bumper” or “magnet” in this sea of molecules that will push or pull them in the desired direction. It is amazing how much control can be exerted over seemingly random processes by a few well-placed “bumpers” or “magnets” in this huge molecular pinball game of life. The “signal beacons” that mark the pathways are often well-placed molecules that simply help nudge the ocean travelers in the desired direction. The “windows”, “doors” and “mailboxes” outside and inside the cells are full of specialized “signaling beacon” molecules that are specially designed to attract or repel only specific kinds of molecules out of the sea of passing molecules, making for a well-marked and designated pathway for certain kinds of molecules. Due to the combined efforts of all these types of well-placed signaling beacon molecules, all the molecules of life are able to successfully navigate the pathways of life in the ocean inside us and arrive safely at their intended destinations, even over what might seem to be astronomical distances on the molecular scale. The true glory and intelligence of the cell lies in how it controls this molecular signaling beacons and the traffic they direct. Five Nobel prizes have been awarded in as many years for work in understanding cell signaling, the implications are incredible.
What are the factors that determine the action of these “signaling beacons” that guide the molecules of life along the myriad pathways traversing the ocean inside us? We find that the real factors that determine these pathways lead us to examine the details of what happens in the local molecular environment surrounding the signaling beacons that mark the pathways. And what happens in the local environment around these signaling beacons is intimately connected to what is happening in the sea of constantly moving water molecules, and islands of charged clusters, surrounding these signaling beacons. So if we want to know the answer, it all comes back around to what happens in the salt-water environment that transmits signals to the surrounding molecules. Again we realize that the critical clues to life are found in what happens in the world of the all-encompassing water molecules. So, how are signals transmitted through this sea of water molecules?
Changing the redox potential or pH in the neighborhood of a “signaling beacon” can change the nature of its signal and thus shift the associated pathway. For a simple analogy, think of a signaling beacon as a “semaphore” floating on a buoy in the middle of the ocean. Changing the redox potential in the water surrounding the signaling beacon can change the “color” of the semaphore, say from green to red. This change of state shifts the “traffic patterns” of the molecules that are directed by this signaling beacon and thus shifts the pathway of millions of the molecules traveling through our internal ocean. This kind of signaling is referred to as redox signaling, it changes the nature of the signaling beacons and redirects the molecular pathways through the ocean of life inside us. There are molecular pathways that control literally every aspect of our existence. Pathways in our brain allow us to store our memories, think our thoughts, feel our feelings, and be aware of everything happening in our body and environment; joining with pathways in our body that beat our heart, breath our air, move our muscles, digest our food, control our metabolism and process billions of signals from every part of our body. We have seen that these pathways allow us to move the molecular materials and supplies needed throughout all of our cell communities. These pathways allow us to deliver the messages between the molecular players in our cells, tissues, organs and systems needed to operate our genes, sustain and maintain cooperation and homeostatic balance between all of our trillions of cells throughout all of our cellular communities.
We have come to an understanding that these life-sustaining pathways must allow molecules and electrical fields to pass through the vast fluid ocean of life that exists inside, outside and between all of our cellular communities and that connects all of the molecular players inside them. Finally we have come to a realization that all of the molecular traffic traversing these pathways through this vast sea of life are controlled by signaling beacons, much like “semaphores”, that determine what happens to the molecular travelers at the trillions of critical junctions or intersections all along the various pathways. We know how insulin and glucagon modify the glucose pathways in the body, for example. We ponder the question “Who controls these signaling beacons?” and find that, beside philosophical considerations, many of these signaling beacons are controlled by signaling molecules that exist in the sea of water molecules that surround them. These signaling molecules modify the state of the various signaling beacons (semaphores) that direct traffic along the molecular pathways. We will consider a special set of these molecules, redox signaling molecules, that are the most fundamental of all of these signaling molecules, composed of the very molecules that form the vast ocean inside us. We have quite a journey ahead of us.


The Harmonious Orchestration of Life


     It is no surprise then, when we consider all of the incredible complexities of life that everything comes down to how the molecules are formed and put together and how they interact inside the living cells and tissues.  The basic fundamental secrets of life, we might suppose, are found in how the molecules themselves are formed, how they interact with other molecules in their environment and how they shift and change over the course of their existence.  It seems a bit strange, at first, to fathom how all life can be composed of molecules, a bunch of whirling particles following a set of physical laws and fields, and how this can lead to sentient, conscious beings that are self-aware, can act for themselves and have learned enough to discover and ponder the very principles that allow themselves to exist.  This might be an open question, yet there is no denying that on the most fundamental level we are composed of molecules and yet we hold within ourselves the breath of life.

     On the most fundamental level, all life brings into itself the elements that it needs to sustain life processes and releases the waste products that are generated.  For humans these basic elements of life are water, nutrition, oxygen, fuel and waste.  Deprive us of any of these elements and we cannot exist.  This is universally true, right down to the cellular level.  After all, it is within the aqueous interior of our cells that oxygen is combined with fuel to create energy, where nutrients are used to build tissues, organs and systems and where waste is created.  Our lungs supply oxygen to our cells, our digestive system provides nutrients and fuels to our cells, our skin, mouths, stomachs and blood vessels absorb the water our cells need.  In short, all of the activities we do to sustain our life involves the necessary processes that bring the elements of life to our cells.  And then it is within the chambers of our cells that these molecular elements are processed into the molecules that are needed and where the energy is released that is needed to sustain the whole process and where waste products are generated and eliminated.  The processes of life are largely performed by self-sustaining, self-actuating molecular engines inside our cells, and the mystery of how this all works and sustains itself resides inside living cells, where the molecular mechanisms of life reside.

      The molecular orchestrations of life in our body are performed in perfect rhythm and harmony, every day, all working together to give us this incredible gift of life.  In an orchestra there are various types of players each trained to play their instruments with precision and mastery.  These players and their instruments can be compared to the masterful, beautifully crafted tiny molecular machines inside our cells.  The players in an orchestra gather together with their instruments, poised to perform their parts; the molecular machines in our cells are gathered together, organized and positioned precisely, ready to perform their part.  The musical score is then copied and passed out to the various players in the orchestra, similar to the way that the instructions within the DNA of our genes are copied into RNA and passed around to the players in our cells.  In the cell, the written music in the score represents the genetic instructions distributed to be performed by the molecular players.  Before the conductor steps onto the platform, the players warm up and practice their individual parts, the result is a dissonant jumble of individual musical lines, each conveying some part of a message, disjoint, confusing; there is no unity, order or sense to it.

     The conductor then steps up and taps his stand.  All the players with their instruments stand at attention and silent anticipation ensues.  All attention is on the conductor as he starts the beat and the instruments begin to play their individual parts at the programmed time.  Something interesting happens at that point.  All of the individual parts come together and start to convey a unified message; instead of individual parts, a harmonious orchestration ensues, each individual instrument now works together with the others to create a much richer and powerful message than would ever be possible with one instrument alone.  The individual parts then “make sense” as they are heard along with the other parts.  All of the instruments interplay in wonderful synchronization toward a singular purpose.

     If an orchestration is successful, a feeling described as “electricity” propagates as instruments, players, orchestra and audience link in to the same beat, the same message, the same emotional response.  There is an almost transcendent feeling unifying hundreds of people that are sharing a single message all conveyed by the vibrating air that surrounds them.  Most all of us have had this experience at one time or another, regardless of the type of music. This feeling may have more to it than it seems.  It appears to be programmed by life itself, it resonates with the harmonious orchestration of life that takes place inside your cells, tissues, organs and systems, trillions of tiny molecular orchestras performing together in remarkable harmony and rhythm, programmed by the “musical score” that is written inside the DNA.  The music is passed around inside the cells by messengers, generating and organizing the players and instruments.  The music is performed by these molecular orchestras performing the program of life inside the cells.  And just like in the orchestra, the real magic happens when a “beat” signal is established and all of these molecular instruments, cells, tissues and systems start listening to each other and acting in harmony, responding to the parts that are being played by the other instruments, each playing their part at the proper time.  Isn’t it interesting that this idea of harmonious orchestration even works on the molecular level, in fact on every level, inside your cells, tissues, organs and systems.  These harmonious molecular orchestrations inside us allow us to live.