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 Breath of Life


The complexity and beauty of life are transformative.  Just a moment’s contemplation of your own hand, observing the complex structure and functionality, the blood vessels, the hair, skin, skeletal  structure, joints, the ability to make it respond to your every command, can invoke a sense of the wonder of how it all works.  If you take the time to look closer, with a magnifying glass or microscope, you will see things you might never knew existed: vast fractured landscapes, hills and valleys.  You may see things that make this supposedly familiar part of you seem foreign: strange, moist valleys, dry wastelands, tiny creatures moving about.  In truth, you would have to spend about a month of exploration just getting to know the back of your own hand, and that is only the top layer of the skin, saying of nothing of the wonders that exist beneath the skin.

Certainly, this concept applies to more than just your hand, the same could be said of all life.  In all honesty, a true understanding of how life works requires a much closer view inside the structure of living things, past the tissues, down into the cells, past the living cell structures and past the bustling activity of thousands of different cellular components, down to the smallest elements of the working internal machinery.  It is here where the secret of life resides and where we might find our answers to how all life works.  Most scientific investigation of things on this small of a scale is relatively recent.  When my father was born, simple, basic cell structure was first being investigated.  When I was born, DNA and its function were first being explored.

During my lifetime, knowledge has grown exponentially to the point where we have mapped the whole human genome and now know almost 1% of the internal workings of a cell.  The acquisition of knowledge is a noble and worthy pursuit, embodying the greatest accomplishments of this century.  Discoveries are being made daily.  My children will possibly live in a day where the majority of fundamental cellular microbiological mechanisms will be known and much of the secret of life revealed.

How and where will the secret of life be found?  In my youth I was taught that an atom was the smallest fundamental unit of all matter.  In my young mind, I reasoned that the mysteries of how all things work must be found in the atom.  I was so enamored by this concept that I ended up studying atomic physics in college and later went on to earn my Ph.D. in that field.  The answers to the universe, I thought, must be found in how the atoms work.  After all, there only exist a grand total of less than 100 stable types of atoms.  Out of those there are only 20 or so necessary for life processes and the vast majority of the molecules of life are combinations of Carbon, Hydrogen, Oxygen, Nitrogen, Phosphorous and Sulfur, only 6 of them.  In the innocence of youth, I reasoned, it should not be too hard to figure out how everything works, it’s like putting together tinker toys or Legos where only a few different types of Legos exist.  I may have underestimated just a bit how many different things you can build with just this limited set of “Legos”.