CAUTION: ENZYMES AT WORK: PART II: CLOTTING
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. Since our cells are made from matter they too must follow the laws of nature as well. Everybody knows that blood carries oxygen, water and nutrients to the tissues of the body to keep it alive. And most people know that without the blood’s ability to clot even slight damage to a blood vessel in a vital organ, like the brain, can cause serious bleeding resulting in permanent debility and even death. There are even some people who know that a well placed clot, blocking the flow of blood to a vital organ, like the heart muscle, can also result in permanent debility and even death. What most people do not understand or appreciate is that the body’s ability to prevent serious bleeding from injury, by clotting, must be balanced against the ability for these same clots to block the flow of blood to its vital organs. In other words, the clotting mechanism that prevents blood loss from vessel injury must turn on only when it is needed or else serious things can happen. This is the reason why almost everybody does not seem to know that, when not resisted by some sort of innovation, the laws of nature do not bring about life, as evolutionary biologists would have us believe, but death. Having the clotting factors be activated at exactly the right moment, to prevent serious blood loss and tissue injury, is a good example of this truth. But before you can understand and appreciate why this is so, you must first learn how clotting actually takes place. So how does the body do it? One of the most important set of molecules in the body is the 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 control clotting so it can survive.
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 they make up the six molecules of carbon dioxide gas (6 CO2) and the six molecules of water (6 H2O) instead.
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 to be 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 slows down or totally blocks 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).
For a video explaining enzymes see: http://highered.mheducation.com/sites/0072495855/student_view0/chapter2/animation__how_enzymes_work.html
Now that we know what enzymes are and what they do let’s see how enzymes work to help the body control its clotting of blood.
Experience tells us that injury to a blood vessel usually results in bleeding. This takes place because, with damage, the pressure that sustains blood flow pushes blood out of the blood vessel. Think of it like what happens when a pipe inside your home bursts. The body normally responds to blood vessel injury with a process called hemostasis, which forms a clot to stop blood loss. Hemostasis involves three processes that take place in rapid succession. First, as soon as the blood vessel is injured, local chemical changes trigger the smooth muscle surrounding it to contract and close off the vessel as much as possible to limit blood loss. Second, the platelets swing into action. Blood has three kinds of cells; red blood cells to carry oxygen to the tissues, white blood cells to fight infection, and platelets to help in clotting. Normally, the chemical environment near the wall of the blood vessel is such that the platelets passing by do not stick to it or to each other. But an injury changes this chemical environment and signals the platelets that are passing by the damaged region to attach to the blood vessel wall and to stick to each other. This platelet aggregation results in the formation of a soft platelet plug. While this is taking place, the third process begins. This involves the clotting factors eventually producing long protein strands called fibrin. These fibrin strands consist of small identical fibrin molecules called monomers that are able to chemically bond with each other to form very large molecular chains called polymers. Like thousands of sticky threads, these long strands of fibrin attach to the platelet plug and wrap around it to form a molecular meshwork that entraps red blood cells and plasma to form a fibrin clot. It is this fibrin clot that is often needed to stop the bleeding and let the blood vessel heal over the next few days.
To see a video that shows what is described above go to this link: https://www.youtube.com/watch?v=8YjmE5UMYvY
But where do the fibrin strands come from? After all, the smooth muscle is already in place, ready to contract and close down the blood vessel to prevent further blood loss and help clot formation when the time is right. And the platelets are already in the blood that flows past the injury site, ready to stick to the vessel wall and to each other to form a plug when called for. So what about fibrin? Think about it! If long sticky fibrin strands were always present throughout the bloodstream they would tend to attach to the walls of small blood vessels and block the flow of blood which would result in organ failure and death. So, fibrin must somehow be in the blood and remain inactive until the right time.
In fact, the liver produces a protein called fibrinogen, also known as (clotting) Factor I. Fibrinogen consists of a few thousand amino acids and remains in solution being prevented from becoming fibrin and joining together to form insoluble polymer strands by specific chemical groups at each end of the molecule. Platelets have receptors for fibrinogen and when activated, to form a platelet plug, thousands of fibrinogen molecules attach to them. What causes the conversion of fibrinogen to fibrin and the formation of clot forming strands of fibrin is the presence of an enzyme called thrombin. Thrombin removes the chemical groups at the ends of fibrinogen thereby exposing bonding sites that allow the fibrin monomers to join together end to end to form the long insoluble polymer strands needed for clotting. Thrombin also activates Factor XIII which allows the fibrin strands to link up across each other as well, significantly strengthening the clot. Thrombin is so good at what it does that one can be sure that wherever it is present, clotting takes place, and wherever it’s not present clotting doesn’t occur.
But, where does the enzyme thrombin come from? Think about it! If thrombin quickly converts soluble fibrinogen into insoluble polymer strands of fibrin, resulting in clot formation, then if it were always present throughout the bloodstream that would result in generalized clotting, organ failure and death. In fact, the liver produces another protein called prothrombin, also known as Factor II, which consists of several hundred amino acids. In the right set of circumstances an enzyme called prothrombinase forms and breaks two chemical bonds in prothrombin to convert it into thrombin which then goes on to convert fibrinogen to fibrin to form a clot.
But where does prothrombinase come from? Think about it! If prothrombinase quickly converts prothrombin to thrombin which then quickly converts fibrinogen to fibrin, then if it were always present throughout the bloodstream that would result in generalized clotting, organ failure and death. Like an air bag in a car or a sprinkler system for fire protection in a building, human survival requires that the clotting factors swing into action only when they are actually needed. In fact, just as smooth muscle contraction and platelet plug formation take place due to changes in the chemical environment brought on by injury to the blood vessel wall, so too, does activation of the clotting factors as well. In general, medical science has determined that there seems to be two different chemical pathways involved in the formation of prothrombinase.
One pathway, called the Tissue Factor (extrinsic) pathway, works very quickly. With vessel damage, the blood, containing inactive Factor VII, comes in contact with Tissue Factor, a protein on the surface of the tissue that supports the blood vessel, and activates it into a protease, an enzyme that can break the chemical bonds within proteins. Activated Factor VII then breaks chemical bonds in Factor X to activate it and when it joins to activated Factor V it forms prothrombinase. The slower pathway, called the contact activation (intrinsic) pathway, takes place due to the direct contact of blood with the damaged tissue and involves many more clotting factors. The contact first activates Factor XII which becomes a protease that breaks chemical bonds to activate Factor XI. Activated Factor XI is also a protease that then activates Factor IX. Activated Factor IX, with the help of Factor VIII, then activates Factor X, which as noted above, joins with activated Factor V to form prothrombinase. Prothrombinase then activates prothrombin into thrombin which then activates fibrinogen into fibrin and clot formation takes place. All of this together is known as the coagulation cascade.
It is the liver that produces most of the clotting factors. In general, each of the clotting factors that work within the different pathways is needed for adequate clot formation. Moreover, since, daily, there are thousands of small injuries to blood vessels requiring fibrin clots to prevent excessive bleeding this means that the liver must continuously produce enough of the clotting factors to prevent serious blood loss. However, at present, the mechanism underlying the regulation of clotting factor production in the liver is unknown.
To see a video that shows what is described above go to this link: https://www.youtube.com/watch?v=cy3a__OOa2M
To see a schematic diagram showing what is described above go to this link: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/Clotting.html
Life And Death And The Laws Of Nature: Real Numbers Have Real Consequences
Due to the laws of nature like friction, gravity and the pressure of blood flow, thousands of small vessel injuries, which can potentially cause blood loss, take place every day in the body. This means that to prevent excessive blood loss the clotting system uses up its clotting factors on a continual basis. The liver produces most of the clotting factors. The normal blood level of fibrinogen is about 3,000 units. But if the fibrinogen level drops below 1,000 units, excessive bleeding takes place because there just isn’t enough to go round. For prothrombin the normal blood level is about 100 units and if it drops below 30 units, the same thing happens as when there isn’t enough fibrinogen, excessive bleeding. For Factor V, the normal and critical numbers are 10 units and 2.5 units, for Factor VII, 0.5 units and 0.125 units, for Factor VIII, 0.1 units and 0.04 units, for Factor IX, 5 units and 1.5 units, for Factor X, 10 units and 2 units, for Factor XI, 5 units and 1.5 units and for Factor XIII, 30 units and 1.5 units. In addition, clinical experience teaches that the absence of fibrinogen, or prothrombin, or Tissue Factor, or Factor V, or Factor VII, or Factor VIII, or Factor IX, or Factor X, or Factor XI, or Factor XIII would have made it impossible for our hominid ancestors to live long enough to reproduce. In other words, without the right amount of each of the clotting factors, the laws of nature prevent the existence of human life.
Points To Ponder
It was the extremely high improbability of any one of the thousands of biologically significant molecules, like the different clotting factors, being formed by just chance and the laws of nature (never mind the need for the untold millions of each one of them to allow for life) that alerted scientists to an intelligent agent within the cells telling them how to make them. This is what first motivated scientists to search for and find the DNA molecule and everything else connected to it that has been, and continues to be, discovered. But, paradoxically, modern evolutionary biologists see all of the information packed into the DNA molecule and still conclude that it all came about by just chance and the laws of nature alone rather than “a mind at work” i.e. intelligence. In other words, scientists, using their ability to detect intelligence, recognized that there had to be an intelligent agent inside the cell instructing it on how and when to produce these complex and vital molecules, but after finding it concluded that this intelligent agent itself had come about by chance and the laws of nature alone. Alternatively, many people now believe and teach that it was nature itself, as the intelligent agent, that through evolution, brought about DNA and all of the innovations needed for life because that was what was needed. They seem to forget that, by definition, evolution, as described by evolutionary biologists, is a blind process which has no goals.
Clotting is a very intricate and complicated process involving several different clotting factors each of which are made up of several hundred or a few thousand amino acids, without which human life would be impossible. Moreover, the clotting mechanism must turn on, work fast enough and have enough effect only when bleeding actually takes place. Furthermore, if too much clotting takes place, or it takes place where it isn’t needed, then blood flow can be seriously compromised and, depending on the blood vessel involved, can result in serious organ damage and even death.
Dr. Michael Behe has called a system where the absence of any one part renders it useless as being irreducibly complex. It certainly looks like the coagulation cascade in humans is irreducibly complex because if any one of the many clotting factors is absent then life would be impossible. However, just having an irreducibly complex system does not automatically allow for survival. As noted above, even if all of the clotting factors are present, if any one of them is not being produced in the right amount or is not functioning properly, then serious bleeding, debility and death would be the result and our hominid ancestors could not have survived to reproduce.
As you can see real numbers have real consequences when it comes to dealing with the laws of nature, like stopping bleeding from a blood vessel. For not just any amount of each of the clotting factors is needed for survival. It has to be the right amount. All clinical experience has borne this out. Besides being irreducibly complex, systems that allow for life must also have a 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 a 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 system the body uses to produce the clotting factors seems to inherently know what is needed to get the job done and does it naturally.
To hear evolutionary biologists tell it, all you have to do is show how each of the clotting factors may have come about from some prior protein by a natural process, such as gene duplication, and that in and of itself should be sufficient to confirm that the coagulation cascade in humans came about solely by chance and the laws of nature alone. But, this is a preposterous notion. It’s like trying to explain how the brake system to stop a go kart eventually developed into one that can stop a dump truck without taking into account everything else that’s different between them. For these innovations, like clotting, did not develop within a vacuum and therefore should not be considered in isolation from what must have been going on within these intermediate organisms for them to survive in the first place. To do so seems to be a tad simplistic and frankly unscientific.
It is interesting to note that evolutionary biologists have come to realize that invertebrates have a clotting system in place that is much simpler than for vertebrates. The pressure within the invertebrate’s circulation is much lower than in a vertebrate’s and therefore does not need as much material to stop blood loss. The clotting material for invertebrates consists of a gel-like substance, almost like the platelet plug, as opposed to the firm and thick fibrin strands needed to stop bleeding in vertebrates. It is thought that the reason why vertebrates require the coagulation cascade is that by activating successive clotting factors this in turn generates the formation of more and more fibrin so there will be enough to fix the damage done in the higher pressure system. And, because of the high pressure system the material needed to close off the injury requires a stronger and thicker material like fibrin rather than the gel-like clot in the invertebrate. It’s like a beaver that has to fix a breach in its dam. If it is small enough with only a trickle of water going through at low pressure (invertebrate) it may only need to use some leaves and sticks joined together by some thin mud. But if the breach is large and has a torrent of water going through at high pressure (vertebrate), the beaver will need to use lots of logs, large branches, sticks, leaves and patch it all together with lots of thick mud to seal the breach. However, this process cannot happen in the vertebrate unless there are enough clotting factors around to be activated in the first place. Evolutionary biologists surmise that at some time or other liver cells adopted the ability that the pancreas cells have to make inactive enzymes and started to make inactive clotting factors. But, despite this theory they never mention how the liver knows how much of each of the clotting factors it needs to produce and how fast it can produce them to prevent the body from bleeding to death. The reason why they can’t do this of course is because medical science has no idea how the liver controls its production of clotting factors, nor almost anything else it produces.
Moreover, nowhere is it discussed by evolutionary biologists how incredibly lucky it was that each new clotting factor was able to activate the next one in each of the different pathways. Nor is it mentioned how fortunate it was for vertebrates that the final product of the coagulation cascade would be a protein (fibrin) with exactly the right properties to do the job that’s needed. Furthermore, like in the scenario of the go-kart turning into the dump truck, nowhere does evolutionary biology even mention how the high pressure circulatory system of the vertebrate, which required this more sophisticated clotting mechanism in the first place, could have gradually developed while the coagulation cascade itself was evolving as well. This would have required several simultaneous innovations, like a heart to pump enough blood with enough pressure, blood vessels with thick enough walls and muscles to deal with the higher pressure so as to not burst, and the control mechanisms for these and the body’s salt and water content as well.
As noted above, given what we know about how life actually works and how easily it dies when it isn’t able to clot well enough, it is evident that for the coagulation cascade to have developed naturally within living organisms that could reproduce, would have required several other simultaneous innovations in other organ systems as well. What those innovations were and exactly how those intermediate organisms were able to control their clotting 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 historical science and evolution and we can only see what is present now. This is one way to explain how clotting may have evolved without having to seriously consider the 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 should be explored before a theory is proclaimed to the public. No, this is faux science and just wishful thinking. It’s also how evolutionary biologists have been able 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, not on ignorance, but on what we actually do know about how life actually works and how easily it dies. But I wholeheartedly agree that, based on the current evolutionary theory of clotting, without consideration of any of the factors mentioned above, that evolutionary scientists 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.
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 beavers just randomly pick whatever is close at hand to fix a breach in their dam? No, when it comes to the origin of life it seems to me that Science still has a lot of explaining to do. Meanwhile, as we wait for evolutionary biologists to admit and stress the deficiencies in their theory our children and the whole world continues to be misled!
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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