God's Biological Plan of Redemption: Molecular Imperfections Made Perfect
"Why me, O Lord?"
This prayer of lament will slip through the lips of 1 out of every 100 Americans above the age of 65 years as they face Parkinson's disease. That number will jump to 5 by age 85. A Parkinson's disease diagnosis spirits the depth of this persistent anguish.
If we were to ask God this question face to face, perhaps we would be reminded that humanity was not designed for this affliction. In fact, the Creator conceived and developed a biological redemptive plan to overcome this pathology. But over time, humans stepped in and unwittingly interfered with God's plan. Toxic pesticides, such as rotenone, and herbicides, such as paraquat, remain high on the suspect list for oxidative stress damage leading to parkinsonism. Also suspect are selected viruses as seen in the pandemic influenza virus of 1918 where great numbers developed symptoms of Parkinson's disease.
Insight into this physically redemptive plan requires us to have a surface understanding of proteins (see sidebar). Let me introduce two of them for you: the sodium channel and the potassium channel. Both are embedded in large quantities within the surface membrane of neurons throughout the brain. Almost single-handedly, they are responsible for generating and maintaining an impulse that allows communication with other neurons.
Impulses start when sodium channels open. Early in the neuron these channels detect a shift in voltage from inside out with as little as 15 one-thousandths of a volt change. Then they promptly open, creating an impulse cascade along the neuron's far-reaching extension, like an avalanche on a mountainside.
With the sodium channel open, a horde of sodium ions rush inside-reminiscent of customers at a department store's annual sale. The door shuts promptly after one one-thousandth of a second. Not many sodium ions actually get through. Just enough to alter the voltage directly on that membrane spot where the channel is located so a 15-millivolt condition is changed to a little over 100 millivolts. This is vital.
If the door were left open any longer, the results would be devastating. A "fast-talking" neuron would begin to stutter. Brain communications would become all jumbled. But it doesn't! That's because the clock inside is perfectly timed. As sodium channels next door and down the extended axon begin to sense these voltage changes, they also open and the avalanche process begins.
As if in perfect community, sodium channels coexist with potassium channels in the same membrane. However the potassium channels are designed a little differently. Unlike their sodium counterparts, they do not detect early voltage. They ignore the change of 15 and respond only to the 100. Then, they open their doors. Like department store shoppers wanting out, potassium ions rush out when the channel opens. It stays open longer, demonstrating a totally different sensor and a totally different clock than seen in the sodium channel.
More amazing still is the selectivity of each channel. Each only lets the proper ion through. In the eyes of a chemist, sodium and potassium are much like identical twins except that one is fatter. The fat one is potassium.
Those sale shoppers overloaded with packages would be analogous to the potassium ion. They need a bigger door (potassium channel) to get through. If that bigger door is now open, what is to keep the smaller sodium ions from rushing in? Yet they don't. The design forbids it. Futhermore, there are a host of "ion strangers" outside and inside the doors that are of adequate size to slip through an open door. The design keeps them out as well.
As you can see in both protein channels, the design is perfectly constructed. A biological clock, still a mystery to neuroscience, is highly tuned - far beyond any Swiss watchmaker's capacity. Entry selectivity is a homeland security's dream. These two proteins are sculpted to perfection both in size and shape.
The cell has literally hundreds of proteins like these two, exquisitely designed, shaped and folded to accomplish a single task. For any one protein, the blueprints are found in a "haystack" of DNA. Blueprint pictures leave the nucleus where DNA has kept them nested away. They enter a factory (endoplasmic reticulum) where strings of amino acids are made and sent to a craftsman (golgi apparatus). The craftsman is somewhat like a balloon artist at a festival. He blows up long balloon strips-twisting, turning, interlocking-and before a child's wide eyes, a giraffe or a dachshund is formed.
Not all goes well all the time. While developing, some amino acid strings do not fold properly. The craftsman in the cell does his best with what is given him, but an unworkable protein is presented as a final product from his shop. At other times, environmental conditions, such as oxidative stress, cause correctly folded proteins to unfold. Damaged proteins can aggregate and form clumps. Parkinson's disease is identified with these clumps (Loewi bodies) in the dopamine system and other regions.
God has developed a breathtaking system to detect misshaped proteins and recycle them. Best scientific judgment suggests 30 to 40 percent of developed proteins are without proper confirmation and must be recycled. This process could be viewed as God's Biological Redemptive Act.
A neuroscientist writing on this system has called it "exquisitely regulated choreography." It is called the ubiquitin-proteasome system. Consider for a moment the choreography of ubiquitin (Ub). Ub is itself a protein, though not very big. It was discovered approximately 15 years ago and its job is to roam the cell identifying improperly shaped proteins.
To help the process, Ub "jumps into a taxi." For the neurobiologist, this taxi is ubiquitin activation enzyme E1. Ub will shortly need a boost more than the taxi can give. Either the roads are too congested or the traffic lights too frequent. Ub transfers from the taxi to a police squad car with red lights and siren. Once again, for the neurobiologist, the police car is the ubiquitin-conjugating enzyme (E2). Ub is now high energy, or as we would look at it, it is ready to make an arrest of a faulty protein. But arrests are not so easy to make. Arrests require validation by witnesses.
One Ub cannot do this by itself, so he transfers to an ambulance (E3). Upon opening the back door, Ub sees a protein on the gurney. Does this protein lack confirmation and ultimately find itself useless, or has the ambulance attendant made an improper judgment? Ub will take a look.
While checking, three police cars pull up and fellow Ubs jump out and enter into the process. The four now join together in assessment. Validation process requires at least four taggings by Ubs (polyubiguination) before allowing admission into the hospital (proteosome). The genetic form of Parkinson's disease, which is rarer, is considered to be caused by an interference of validation by four Ubs so that faulty proteins begin to build up.
Admittance into the hospital is demanding. If any one of the four Ubs fails to approve, the protein will be rejected at the desk. When they all agree, the proteosome will accept the protein and begin to break it down so it can be reconstructed again in a useable fashion. The team has succeeded. But how did they know a protein was improperly shaped? Without eyes to see, what triggered the team's decision? Science is certainly addressing this question. One thing is certain-God's planning is incomprehensible.
The team will not stay together long. A debiquinating system will break them up. They will go back as single Ub molecules ready to start all over again, getting into a taxi and becoming energized. The hunt for improperly shaped proteins is going on every moment of every day in every cell of your body.
Great is Thy faithfulness, O God our Father.
Arvin Oke is a fellow and collaborative research scientist at the Morris K. Udall Center of Excellence in Parkinson's Disease Research located at the University of Kentucky. He also serves as part-time professor of psychology at MidAmerica Nazarene University in Olathe, Kansas.
Proteins are literally the molecular workers in the body, carrying out almost every activity in the body ranging from antibodies to enzymes, muscle to blood. They are components within a cell doing the necessary tasks for it to function. They are channels on cell membranes becoming gatekeepers for selected agents like glucose channels allowing only sugar into the cell. They are receptors sensing information from hormone messengers and neurotransmitters.
Proteins come in various sizes and shapes. Like words made from letters of the alphabet, so proteins are made from amino acids. Curiously, 20 amino acids compare with 26 alphabetical letters. In both, orderliness is mandatory. Sequence makes letters into words and sequence makes proteins from amino acids. An additional feature, more prominent in the Chinese language than English, is shape. Misshaped proteins are biologically inactive. It is the three-dimensional shaping of proteins that still mystifies science.
Holiness Today, September/October 2010.