CAUTION: ENZYMES AT WORK
PART VI: MOMENT TO MOMENT CONTROL
We live in a world made from matter. Matter is made up of atoms and molecules that follow the laws of nature. All life is made up of atoms and molecules that are organized into cells. Our body has trillions of them. Everyone knows that to have moment to moment physical control requires being able to slow down and stop what we’ve started. And although many people know that hormones are needed for metabolic control, and some even know that this requires sensors to detect what needs to be controlled, integrators to decide what needs to be done and to send hormonal messages to do it, and effectors, with receptors, to receive these signals and do what needs to be done, this alone is not sufficient to provide moment to moment control. What most people do not understand, nor appreciate, is how the body is able to maintain moment to moment control by being able to slow down or stop what it has started. One of the most important sets of molecules in the body are enzymes. Let’s first look at what enzymes are and what they do and then we’ll be able to better understand how they help the body maintain moment to moment control.
Enzymes are special molecules (mostly proteins) that are made in the cell which help other molecules undergo chemical reactions when they come in contact with each other. When these reactions occur energy is either released or used up and different molecules are produced. Every biochemical process in the body requires enzymes to work properly.
Molecules are made up of atoms joined together by chemical bonds. There are very small molecules, like molecular oxygen, which is made up of two oxygen atoms joined together (O2) and water, which is made up of two hydrogen atoms joined to one oxygen atom (H2O). There are also slightly larger molecules, like glucose, a sugar that is made up of six atoms of carbon and oxygen joined to twelve atoms of hydrogen (C6H12O6). And there are very large molecules, like carbohydrates, fats, and proteins, many of which are made up of hundreds or even thousands of atoms joined together.
When molecules meet up with each other they sometimes react. A reaction between molecules simply means that chemical bonds between atoms are created and destroyed. This usually causes some of the atoms in the reacting molecules to change places with each other to form different molecules. Enzymes help chemical bonds be destroyed in larger molecules to form smaller ones and be created between smaller molecules to make larger ones. During this process energy may be released or used up. At the end of the reaction the enzymes are not altered so they can continue to promote more reactions. And, the total number of atoms present in the molecules that are produced at the end of the reaction is the same as there were in the molecules that reacted in the first place. In other words, in a chemical reaction no new atoms are created or destroyed, just the bonds between them, and this often results in the release or use of energy and the atoms involved changing partners to form different molecules.
One important example of a chemical reaction that occurs within our cells involves how they get the energy they need from the chemical bonds within the glucose molecule. Cellular respiration uses specific enzymes to help breakdown one glucose molecule (C6H12O6), in the presence of six oxygen molecules (6 O2), to release the energy the cell needs, while at the same time producing six carbon dioxide molecules (6 CO2) and six molecules of water (6 H2O). Notice that the chemical reaction starts off with a total of six carbon atoms, twelve hydrogen atoms and eighteen oxygen atoms from one molecule of glucose (C6H12O6) and six molecules of oxygen gas (6 O2). And it ends up with the same amount of carbon, hydrogen and oxygen atoms, but instead, they make up six molecules of carbon dioxide gas (6 CO2) and six molecules of water (6 H2O).
The laws of nature determine how fast specific molecules will react with each other. But the addition of an enzyme makes this reaction take place much faster. By speeding things up, enzymes help to produce many more new molecules, usually in the order of thousands or millions of times more, than what would normally happen at random. This is why enzymes are called catalysts. They help bring molecules together to react much faster than what would happen if they were dependent on the random forces of nature alone.
If our body were left only to the random laws of nature the thousands of chemical reactions we need to help keep us alive would not take place fast enough and we would die. Enzymes can catalyze chemical reactions because their specific chemical nature and shape allows them to bring specific molecules together to react in a specific way. This is similar to how hormones have their specific effect(s) in the specific cells of specific target tissues by locking on to specific receptors (see prior articles entitled Caution: Hormones at Work). It is also important to note here that the body also produces different proteins called “enzyme inhibitors” as well. It is the specific chemical nature and shape of the enzyme inhibitor that enables it to bind to a specific type of enzyme and by doing so either slow down or totally block its metabolic effect. Enzyme inhibition is one of the ways the body is able to control many of its metabolic processes.
There are thousands of different enzymes in the body each of which have a specific effect on a specific molecule. As noted above, it is the shape and chemical nature of the enzyme that determines which molecules it will work on and what type of reaction it will catalyze. The first part of the chemical name of an enzyme usually indicates the specific molecule or class of molecules for which it catalyzes reactions. And the last part of its name usually ends in “ase”. For example, lactase is the enzyme that helps to breakdown lactose, a sugar in milk that is made up of one molecule of glucose joined to one molecule of galactose. And a protease is a class of enzymes that helps to breakdown proteins which are made up of two or more amino acids joined together.
The body often uses several specific enzymes in a specific order (pathway), in a chain reaction, to bring about what is needed for survival. The first molecule undergoes a reaction catalyzed by the first enzyme, and one of the products of that reaction becomes the second molecule in the pathway. The second molecule, in turn, undergoes a reaction catalyzed by the second enzyme, and one of the products of that reaction becomes the third molecule in the pathway. The third molecule, in turn, undergoes a reaction catalyzed by the third enzyme, and one of the products becomes the fourth molecule in the pathway, and so on. This process continues until the required molecule is produced so it can do what the body needs it to do. Note that if any one of the enzymes in the chemical pathway were to be missing or not working properly then not enough of the final product would be produced and life could hang in the balance.
Finally, it is important to understand that since enzymes, themselves, are made up of hundreds, or thousands, of atoms chemically bonded together, their chemical stability and capacity to work properly can be affected by the laws of nature as well. Things like temperature, hydrogen ion concentration and the body’s water content can affect the chemical structure of enzymes. When any of these three important parameters falls out of the normal range the enzymes in our body start to malfunction and so does our body. Serious deviations can even result in death. That is why our body must be able to control these three, and other vital parameters to allow us to survive within the laws of nature. (see prior articles called Caution: Hormones At Work).
Now that we know what enzymes are and what they do let’s see how enzymes work to help the body maintain moment to moment control.
Moment to Moment Control
Moment to moment control begins with a purposeful action. Little Red Riding Hood needs to go up and over a hill to visit her grandmother whose house is just a few hundred yards from the bottom, so she presses on the accelerator to give her car the gas it needs to do so. The body needs to store the excess glucose it takes in after a meal otherwise it will spill out into the urine, so the pancreas sends out insulin to do so. Little Red Riding Hood senses whether the car is going to make it up and over the hill and by integrating this data is able to adjust how much gas she gives the engine so her car makes it to her grandmother’s house. Similarly, the glucose receptors in the beta cells of the pancreas detect the blood glucose level and by integrating this data send out enough insulin into the blood where it goes to the liver cells and attaches to specific receptors to make them store enough glucose to keep the blood glucose from going too high. However, experience teaches that if Little Red Riding Hood doesn’t give her car enough gas or her car’s engine doesn’t have enough horsepower to overcome the natural forces of inertia, friction, wind resistance and gravity then she won’t be able to get her car up and over the hill to visit her grandmother. So too, clinical experience teaches that if the pancreas can’t send out enough insulin, or the liver doesn’t respond well enough to it, then the blood glucose will remain too high and will spill glucose out of the body through the urine resulting in a serious metabolic condition called diabetes mellitus.
But, if Little Red Riding Hood’s car is able to go up and over the hill how does she then maintain moment to moment control so that she ends up at her grandmother’s house? After all, Little Red Riding Hood does have a specific destination and she must get there without wrecking her car. Similarly, if the pancreas sends out enough insulin and the liver responds properly then how does the body maintain moment to moment control of its blood glucose? After all, not only is having too high of a glucose level not good for the body, but so is having too low of one as well, since this can result in brain malfunction and even death. Since the body is always using up glucose to provide it with the energy it needs for its various activities, and is often receiving new supplies of glucose from the digestive system, the body’s blood glucose is always in a state of flux. So, to prevent it from having too low or too high a blood glucose, the body must be able to maintain moment to moment control. This not only applies for glucose but also for many of the body’s other vital chemical and physical parameters (e.g. oxygen, hemoglobin, water, sodium, potassium, calcium, blood pressure, core temperature and hydrogen ion (acid)). So how does the body do it?
One aspect of moment to moment control involves trying to apply the right amount of force, or action, for what is needed and then letting nature takes its course. Little Red Riding Hood knows that she has to get her car up and over the hill and beyond to get to her grandmother’s house. So she tries to give her car enough gas to overcome the forces of nature to get it up and over the hill. But once she makes it to the top she knows that, as nature takes its course, her car’s momentum, now aided by gravity, will continue to move it down the hill towards her grandmother’s. The problem Little Red Riding Hood faces (besides the wolf) is how to apply just the right amount of gas to get up and over the hill and then down it without having her car’s momentum overshoot the mark and carry her right past her destination.
Similarly, in response to rising blood glucose, the pancreas sends out a specific amount of insulin. The insulin travels in the blood to the liver, attaches to the specific receptors on its cells, and tells them to store glucose. In doing so, the insulin gets used up. In other words, after the specific amount of insulin attaches to the receptors on the liver cells, it no longer has any further metabolic activity. But, as nature takes its course, the storage of glucose in the liver, at the direction of the specific amount of insulin, will cause the blood glucose to drop, and as noted above, having too low of a blood glucose can cause death. The problem the pancreas faces is how to send out just the right amount of insulin to bring the blood glucose down without overshooting the mark and making it go too low.
I think it is safe to say that the chances of Little Red Riding Hood being able to apply just the right amount of gas so her car will stop on its own at her grandmother’s house by letting nature takes its course are nil. So too, the chances that the pancreas will put out exactly the right amount of insulin to keep the blood glucose from staying too high while at the same time not going too low are just as unlikely. Clearly, moment to moment control of anything, whether it’s a car going up and over a hill to a specific destination, or the body maintaining its blood glucose level within a specific range, requires much more than just initially applying the right amount of force or action and then letting nature takes its course. Experience teaches that the using up of momentum by a moving object or the diminishing activity of a hormone as it attaches to specific receptors cannot in and of itself provide moment to moment control. Let’s see what else is needed.
Another way to help maintain moment to moment control is to have a mechanism in place that produces a force or action that is opposite to the initial one. For example, each bone in the body is set up so that for every muscle that can move it in one direction there is a complementary one that can move it in the opposite direction. This is partly how we can maintain moment to moment physical control, especially when doing precise work. To apply this type of help, for moment to moment control, Little Red Riding Hood would have to be able to suddenly shift her car into reverse at the right moment as her car’s momentum made her pass by her grandmother’s house. And, if she had to apply some more gas going backwards she could overshoot it again and would then have to suddenly shift back into drive. These forward and backward actions would need to be done, literally ad nauseum, until the car came to rest at her destination. The problem that Little Red Riding Hood faces is trying to apply just the right amount of gas, whether going forwards or backwards, to end up at her destination without ruining her transmission.
Similarly, as opposed to a rising blood glucose and the release of insulin, in response to a given low blood glucose, the alpha cells of the pancreas send out a specific amount of a hormone called glucagon. The glucagon travels in the blood to the liver, attaches to specific receptors on its cells and tells them to release stored glucose. However, just like with Little Red Riding Hood’s car going in reverse, the amount of glucagon sent out at a specific moment causes a specific action in the liver which causes the level of blood glucose to rise and may overshoot the mark by going too high. To maintain moment to moment glucose control, the problem the pancreas faces is trying to send out the right amounts of both insulin and glucagon while taking into account the constantly changing blood glucose due to the body’s activity level and the ongoing absorption of glucose from the digestive system.
One can see that the addition of a mechanism that can reverse what the initial force or action starts clearly adds another level of control. Little Red Riding Hood can, if her transmission allows, put it in and out of reverse and drive until she stops at her destination. Similarly, the body can start to get better control of its blood glucose if it is at the same time sending out a certain amount of insulin in response to high levels of glucose and glucagon in response to low levels of glucose. But, just like with Little Red Riding Hood, the body is likely in for a very bumpy ride. There is however one more very important and obvious part that needs to be added to the puzzle to provide Little Red Riding Hood and the body with a smoother and much more controlled situation.
Being able to play “Simon Says” teaches us that to have moment to moment physical control of the body requires us to be able to slow down and stop what we have started. This is the most important component of moment to moment control. Little Red Riding Hood must not only give her car enough gas to go over and down the hill to reach her grandmother’s house but she must also be able to slow her car down and stop it by applying the brakes. Even if she accidentally overshoots her grandmother’s house she can safely shift her car into reverse, press on the gas and apply her brakes again to be sure she stops at her destination.
Similarly, the pancreas is always sending out a variable amount of insulin and glucagon in response to the body’s ever changing blood glucose level. The blood glucose is affected, not only by these two and, to a lesser degree, other hormones, but also by how much glucose the body is using for its present level of activity and how much is being brought in by the digestive system. Having the pancreas send out specific amounts of insulin and glucagon at a specific time in response to a specific level of blood glucose in and of itself cannot provide moment to moment control. The third component, the one that applies the brakes to slow down and even turn off the metabolic effect of a specific amount of insulin or glucagon is the enzymes.
Certain enzymes located in the liver, the tissues and the bloodstream lock-on to specific hormones and are able to chemically deactivate them. For hormones like insulin and glucagon the time for their serum concentration to be cut in half (half-life) is in the order of five minutes. This means that the metabolic effect of a specific amount of insulin or glucagon will be reduced to one half in five minutes, to one quarter in ten minutes and to one eighth in fifteen minutes. Therefore, due to enzymatic deactivation, no matter how much insulin or glucagon is released at a given moment, it will only have an effect in the tissues for just a few minutes. By being able to slow down and literally stop the effects of a given amount of insulin or glucagon, that has been released at a specific time in response to a specific level of blood glucose, this adds the final piece to the puzzle of how the body is able to maintain moment to moment control of its blood glucose.
It is important to realize that, just like for insulin and glucagon, the body needs enzymes to limit the activity of many other hormones and neurohormones so it can maintain moment to moment control to stay alive. One example of this is acetylcholine and its enzymatic deactivator acetylcholinesterase. Acetylcholine is a very important neurohoromone that is present within the brain, the spinal cord and the peripheral nerves which works within the autonomic nervous system to control heart rate, blood pressure, blood flow, sweating, gastrointestinal function and the skeletal muscle system as well. In other words, many of the nerves that provide involuntary control of our organs require acetylcholine to work properly, and our motor nerves release acetylcholine to tell our muscles to do what we want them to do. Without acetylcholine the body could not live.
But what happens if there is too much acetylcholine? Normally, acetylcholine is rapidly broken down by acetylcholinesterase. In fact the half-life of acetylcholine is only a minute or two. Organophosphates, like insecticides and Sarin gas, irreversibly block acetylcholinesterase and stop it from breaking down acetylcholine. This results in too much acetylcholine being present in the autonomic and neuromuscular systems. The effect is to initially overexcite and then paralyze both systems. What starts off as severe flu-like symptoms such as abdominal pain, vomiting and dizziness usually progresses rapidly to confusion, coma, respiratory failure and death.
To summarize: prior articles (see Caution: Hormones At Work) have shown that a sensor, an integrator and an effector are needed just to be able to start to have control. The body uses numerous different hormones and neurohormones to help do this. But experience teaches that that just isn’t enough. Moment to moment control requires the ability to slow down and even stop what you’ve started. In some situations the body uses complementary systems (like insulin and glucagon) to offset each other in order to refine its control. But the main way the body maintains moment to moment control is to limit the effects of its hormones and neurohormones by enzymatic breakdown and deactivation.
Points to Ponder
For the body to survive within the laws of nature it must maintain moment to moment control of several different chemicals and physical parameters. These include things like oxygen, carbon dioxide, hydrogen ion (acid), water, sodium, potassium, calcium, blood pressure and flow and core temperature. In addition, the body must maintain moment control of its nerves and muscles as well. This cannot be accomplished without the presence of many different sensors, to detect what needs to be controlled, integrators, to analyze the data from the sensors and decide what needs to be done, and effectors, with receptors, to receive the messages from the integrators and do what is necessary. In some circumstances, competing systems, which work in opposition to each other, are present to help bring about better control. But clinical experience teaches that, without enzymes to breakdown and deactivate hormones and neurohormones, to slow down or stop their effects, moment to moment metabolic and neuromuscular control of the body would be impossible.
Loss of moment to moment control of any one of the chemical and physical parameters mentioned above will lead to death. Therefore, all of the sensors, integrators, effectors, complementary systems and deactivating enzymes must be present and working properly for human life to exist. Dr. Michael Behe has called a system where the absence of any one part renders it useless as being irreducibly complex. Each of the systems our body uses for metabolic and neuromuscular control demonstrates irreducible complexity. But, that in and of itself is not enough to explain human survival within the laws of nature. For, not only must all the parts be properly connected together and working right, they must also keep each of these chemical and physical parameters within a specific numerical range.
Real numbers have real consequences when it comes to dealing with the laws of nature. For, not just any level of oxygen, carbon dioxide, hydrogen ion (acid), water, sodium, potassium, calcium, blood pressure, blood flow and core temperature is needed for survival. All of clinical experience teaches that it has to be the right one to keep the body alive. And experience tells us that if our earliest ancestors’ nerves and muscles weren’t working properly then there’s no way they would have been able to win the battle for survival.
Just because a system is irreducibly complex does not automatically mean it will be able to function well enough to allow for life. Besides being irreducibly complex, systems that allow for life must also have natural survival capacity. By this I mean that each system must give the organism the capacity to survive by taking into account the laws of nature. This usually involves having knowledge of what is needed to keep the organism alive within the laws of nature and then being able to do what needs to be done. The systems that use hormones and neurohormones and the specific enzymes that deactivate them to maintain moment to moment metabolic and neuromuscular control seem to inherently know what is needed to get the job done and they do it naturally.
Recently, my son Matt, who is a chemical engineer, described for me how they control things in some of the work he does. See if you can pick out the same components (sensor, integrator, effector, deactivating enzymes) the body uses to maintain moment to moment control in his description below.
Here’s basically how a control system works. First, you have the sensor. The sensor is going to detect the variable that you want to control. This could be flow rate, temperature, pressure, tank level, etc. In a control loop, this sensor typically has an analogue feedback, like 4-20 mA (milliamp). So that means at the lowest range of its sensing capability, it will send a 4 mA signal. And at the highest end of the range, it will send a 20 mA signal. Now this signal has to go somewhere. So next, you have the PLC (Programmable Logic Controller). The PLC is part of the computer system and acts like the brain for the control loop. Through wiring back to the PLC, it accepts the input signal from the sensor to determine where the variable currently is. The next thing the PLC does is to compare the input signal from the sensor with the desired set point. The set point is typically entered into the computer by the operator through the HMI (Human-Machine Interface) or FED (Front End Display), two terms used to describe the same equipment. Now the PLC has an input signal and a set point. Inside the PLC, there is software called the PID Controller (Proportional-Integral-Derivative). Basically, this programming is what the PLC uses to determine how to get the input from the sensor signal to match the set point. Within the programming, there are parameters set specific to the application that the software is controlling. So, once the PLC figures out how to change the variable using the PID software, it will then send out an output analogue signal, like 4-20 mA.
Now, back in the field, probably not too far from the original sensor, you will find a device. This device is what will control the variable. In my line of work, this is typically a valve assembly that will proportionally open or close a valve. The simplest example would be increasing flow rate through a pipe by opening the valve. Other examples would be increasing temperature by opening a steam valve that heats the reactor or decreasing temperature by opening a cooling water valve. In any case, this valve assembly is equipped with a positioner, which will accept the 4-20 mA signal from the PLC and adjust the valve accordingly. Typically, 4 mA is valve 0% open, and 20 mA is valve 100% open. So the positioner controls the valve, and the valve directly impacts the variable you are trying to change until it reaches the desired set point. This closes the control loop. The parameters for the PID controller are specific to the application, and so manual testing is done beforehand in order to determine key factors in the control process, including how much the valve has to open to change the variable, and also the time delay between the valve opening/closing and the sensor picking up a change in the variable.
In the examples we discussed, flow rate changes will be picked up by the sensor relatively quickly (1 second) as long as the sensor is installed close to the valve assembly. Typically, a more aggressive programming would be used in this case because of the responsiveness of the loop. Think about the cruise control on your car. You start rolling downhill and the speed goes up. Your car immediately lets off the gas until the speed drops back to your set point. This is because applying or letting off the gas has an immediate impact on the speed of your car. Now, imagine that your car is not as responsive. Instead of a fraction of a second, let’s say your speed sensor takes 10 seconds to send the changes in speed to your car’s computer system. Now, you go downhill, and your car is still giving gas because the computer still thinks you’re at the set point. Next thing you know, there’s a cop pulling you over because you were speeding. Not so good when you want a very aggressive control loop to maintain a strict set point.
Now, let’s imagine the opposite. Let’s say applying gas doesn’t result in an immediate change in speed. Let’s say it takes 10 seconds from the time you put the pedal lower to see the effects on speed. Well, now, if you have an aggressive loop, as soon as you drop below your set point, your car is going to floor it. The computer will see your speed and the set point do not match. So, it will give gas to make up the difference. If it’s expecting an immediate result, it’s going to keep giving more and more gas. Well, when that 10 seconds is up, your car will probably drop to first gear and red line up to 8000 rpms. A more conservative program would account for the time delay and prevent such a knee jerk reaction. This is typically the preferred situation for temperature adjustments because of how long it takes to heat and cool media, especially water. This would be equivalent to your car not seeing the immediate result from applying gas. Even in the case of temperature though, many times it’s easier just to manually control the valves because the operators will have previous experience to know how much to open the valve and how long it takes to heat up or cool down.
Given what we know about how life actually works and how easily it dies when it doesn’t have the right combination of hormones and neurohormones and the enzymes that deactivate them, it is evident that there must have been several innovations within intermediate organisms with respect to how an organism could maintain moment to moment control. What those innovations were and exactly how these organisms were able to live and maintain moment to moment control in these intermediate phases may never be known. This is because further changes which may have come about have since gone by the wayside of evolution and we can only see what is present now. This is one way to explain how moment to moment control in the body may have evolved without having to seriously consider the bimolecular physiology of the now extinct intermediate organisms. But this is not Science, where every aspect of the reverse engineering needed to come up with a plausible explanation for life should be explored before a theory is proclaimed to the public. No, this is just faux science and wishful thinking. It’s also how evolutionary biologists have been able to convince themselves, and others, of the supposed irrelevance or even impossibility of irreducible complexity. Some scientists have argued that the positions of intelligent design and irreducible complexity are arguments from ignorance which lack enough imagination. I would submit that the concerns put forth above are based on, not ignorance, but what we actually do know about how life actually works and how easily it dies. But I wholeheartedly agree that based on current evolutionary theory in the face of the incredible complexity of life that the scientists involved do indeed have very good imaginations. Alas, we who believe that the design seen in nature is real, and not an illusion, are forced to limit our imaginings to what is already known about what it takes for life to survive within the laws of nature. Case in point is the innovation of having enough specific enzymes to deactivate the hormones and neurohormones in the body so it can maintain moment to moment control.
The laws of nature have put up many obstacles to prevent life from existing. Just as a car can die from not having enough gas for energy, or oil for seizing parts, or anti-freeze for engine overheating, so too, all physicians know that there are many different pathways to death. If you really want to begin to understand how life came into existence, you first have to understand how easily it can become non-existent. Did life really come about solely by random chemicals coming together to form cells, then simple organisms, and then complex ones like us? In other words, without “a mind at work” to make it happen? Do you think that, given enough time, the control systems that chemical engineers use, like the ones my son Matt described above, could eventually have come into being solely by the random forces of nature? No, when it comes to the origin of life it seems to me that Science still has a lot of explaining to do. Meanwhile, our children and the whole world continue to be led astray!
Be sure to catch all of the articles in Dr. Glicksman's series, "Beyond Irreducible Complexity."
Howard Glicksman M. D. graduated from the University of Toronto in 1978. He practiced primary care medicine for almost 25 yrs in Oakville, Ontario and Spring Hill, Florida. He now practices palliative medicine for a Hospice organization in his community. He has a special interest in how the ethos of our culture has been influenced by modern science’s understanding and promotion of what it means to be a human being.
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