, , , How Homeopathy Works? A ‘Working Hypothesis’ That Could Be Verified Using Scientific Methods | HOMEOTODAY

The Simple Science of Homeopathic Therapeutics
In this article, I do not endeavor to answer the most commonly asked question whether homeopathy works. It is an already well answered question, even though skeptics go on asking it again and again only to discredit homeopathy. According to my long years of experience with homeopathy, I am fully convinced it works beyond any doubt. However, all those millions of  ’clinical evidences’ we provide will be ‘acceptable’ to scientific community, only when we succeed in explaining and proving ‘how it worked’. Here I am trying to address the question ‘how homeopathy works’, since I consider it as the most vital point to be resolved first. To be recognized as a branch of medical science, I think we have to be successful in explaining the molecular mechanism of homeopathic therapeutics in a way fitting to the existing modern scientific knowledge system, and proving our explanations according to scientific methods.
I know, whatever be the experiences, claims and explanations of homeopathic community, scientific community still considers homeopathy as ‘pseudo-science’. Wikipedia says: “Homeopathy is a system of alternative medicine based on the belief in giving a patient with symptoms of an illness extremely dilute remedies that are thought to produce those same symptoms in healthy people. These preparations are often diluted beyond the point where any treatment molecule is likely to remain. Studies of homeopathic practice have been largely negative or inconclusive. No scientific basis for homeopathic principles has been substantiated”.
For the last 250 years since its inception, homeopathic theoreticians were trying to explain the ‘modus operandi’ of potentized homeopathic medicines using one or other hypotheses available or evolved by them. They go on spinning diverse types of fanciful ‘theories’ using ‘ultra-scientific’ jargons, that make homeopathy a piece of unending mockery before the scientific community. Actually, nobody could so far even propose a scientifically viable ‘working hypothesis’ about homeopathy, that could be presented as a reasonable candidate for verifications according to scientific methods.

Homeopaths falsely claim all their fanciful ideas and explanations to be ‘theories’ and ‘hypotheses’. Scientifically, the term ‘hypothesis’ means a ‘proposed explanation’ or “educated guess” for a phenomenon that we observe around us. Every ‘proposed explanation’ cannot be considered a ‘scientific hypothesis’. To be a ‘scientific hypothesis’, the scientific method requires that one can test the hypothesis using available scientific tools and methodology. Every new scientific hypotheses are generally based on previous observations that could not be satisfactorily be explained with the existing scientific theories. The words “hypothesis” and “theory” are often used synonymously in common and informal usage, even though a ‘scientific hypothesis’ is not exactly the same as ‘a scientific theory’. A hypothesis should be proved ‘using scientific tools’ in order to become a scientific theory.
A ‘working hypothesis’ is a provisionally accepted hypothesis that is ready to be proved. Experimenters will have to test and reject several hypotheses before solving the given problem ultimately. Testability (using existing scientific tools), Simplicity (avoiding excessive numbers of entities), Scope (apparent application of the hypothesis to multiple cases of phenomena), Fruitfulness (hypothesis may help to explain further phenomena in the future), and Conservatism (fitting with existing recognized knowledge-systems) are considered to be the essential qualities of a good scientific ‘working’ hypothesis.
Viewing from this standpoint, it is very much clear that most of the presently existing most celebrated ‘theories’ regarding homeopathy cannot be even considered as ‘scientific hypotheses’ since they contain concepts and conclusions that ‘could not be tested by any scientist using currently available scientific tools and methodology’ or  do not ‘fit with existing recognized knowledge-systems’.
When attempting to provide a scientific explanation to homeopathy, first we have to propose a ‘scientific hypotheses’. That means, a hypothesis that ‘could be tested by any scientist using currently available scientific tools and methodology’ and that ‘fits with existing recognized knowledge-systems’.
Such a ‘working hypothesis’, over and above the aforesaid qualifications, should also be immediately useful to the practitioner, because homeopathy is a therapeutic art of practical implications. Besides lending the essential scientific credibility to the homeopathic paradigm, any hypothesis we propose should try to meet some practical utility criteria as a minimum requirement.
There are already many imaginative and ‘scientific’ ‘theories’ going around that seek to explain everything about homeopathy but fail to predict or offer anything of relevance. If a hypothesis fail to predict some relevant practical outcomes, then it becomes scientifically untestable,  and therefore, unusable in practice.
Assumptions being proposed by a scientific hypothesis should be simple, testable and their numbers should be held to a minimum. The assumptions should also reflect the basic experience that is already generally held to be known.
Any working hypothesis about homeopathy should clearly identify a ‘biological mechanism’ that represents the action-reaction homeostasis of ‘vital processes’, and explain the molecular mechanism of homeopathic therapeutics on that basis, instead of the unscientific  ‘vital force’ theory in homeopathy. Such an explanation  should be fitting to the verified scientific paradigm of modern biochemistry and molecular biology.
Once a ‘working hypothesis’ is proposed, there is much more research to be done before that is accepted as a ‘scientific theory’. The hypothesis needs to offer predictions that can be repeatedly and conclusively proved or disproved in the laboratory and in the clinic with out any bias.
I think it would be helpful at this point, if I provide a abstract of the ‘working hypothesis regarding how homeopathy works’ proposed by Dialectical Homeopathy:
As per the concepts proposed by Dialectical Homeopathy, homeopathic potentization involves a process of ‘molecular imprinting’. This is exactly similar to modern technology of ‘molecular imprinting in polymers’ done in polymer chemistry. Essentially, ‘molecular imprinting’ is a way of creating recognition sites in polymeric materials. Only difference is that instead of polymers, homeopathy utilizes water/ethyl alcohol mixture as the imprinting matrix.
Our concept of ‘molecular imprinting in water’ is based on the available knowledge regarding supra-molecular properties of water, hydrogen bonding, water clusters, clathrate phenomenon etc. Water exhibits some ‘polymer-like’ properties at supra-molecular level, which make it an ideal medium for molecular imprinting. Individual constituent drug molecules act as ‘guest’ molecules and water/ethyl alcohol molecules act as the ‘host molecules’ in this imprinting protocol. Through the process of serial dilution and succussion, water/ethyl alcohol molecules forms supra-molecular clusters, into which the configuration of individual ‘guest’ molecules are imprinted as 3D nanocavities, which are exactly complementary in shape to the ‘guest’ molecules.
Dialectical Homeopathy tries to explain homeopathic therapeutics utilizing the modern scientific understanding of molecular kinetics of bio-molecular interactions. According to this view the phenomenon of ‘life’ consists of complex chains of inter-dependant biochemical pathways called ‘vital processes’ which are mediated by diverse types of protein molecules. There is no ‘life’ with out these bio-molecular interactions and conversions. According to the role they play, molecules participating in these chemical processes are called either ‘ligands’ or ‘targets’. Any bio-molecular interaction takes place in two distinct stages. In the first stage, ‘functional group’ of a ‘ligand’ molecule identifies an appropriate  ‘target’ molecule having a configuration complementary to it, and binds to it. Second stage involves the real chemical interaction, which is determined by the specific charges carried by ‘ligand’ and ‘target’. Foreign molecules having ‘functional groups’ having configuration identical to ‘ligands’, with out appropriate charge affinity, can ‘mimic’ as the real ligands and bind to the targets, with out any chemical interaction or molecular conversion taking place. This phenomenon of incomplete molecular interactions plays a great role in pathological molecular blocks.
Homeopathic therapeutics utilizes this ‘key-lock’ mechanism involved in ‘ligand-target’ interactions. ‘Molecular imprints’ prepared in water/alcohol matrix  with configuration complementary to the pathogenic molecules are used to bind them and inactivate them, thereby effecting a therapeutic action. ‘Molecular imprints’ of drug molecules are the real active factors of potentized drugs. When introduced into the organism, due to the complementary relationship, these ‘imprints’ can bind to ‘pathogenic’ molecules having configuration similar to the original drug molecules used for imprinting. By this process, the biological molecules are relieved from the molecular blocks created by pathogenic molecules, thereby rectifying the pathologic molecular deviations happened in the biochemical pathways.
Let biological molecules be represented by ‘M’, and pathogenic molecules or xenobiotics by D.
Xenobiotics and pathological molecules bind to biological molecule M to form a pathological molecular complex MD. MD represents a pathological molecular error.
Therapeutic process involves with relieving of M from D.
Let crude drug molecules be represented by ‘D1’, If  D1 can produce symptoms similar to pathological symptoms produced by D, that means D and D1 has similar molecular configuration, and they could attack same biological molecules and create similar  molecular errors in the organism. We say D1 is similimum to MD which is caused by D.
Molecular imprints of D1 may be represented by ‘d’, with a 3D configuration complementary to D1.
If D1 is siimilimum to D, molecular imprints ‘d’ will be having complementary relationship to D also.
When applied as a therapeutic agent, ‘d’ can specifically bind to D of the MD (pathological complex) to form Dd (xenobiotic-imprint complex) , thereby  relieving M from pathologic molecular blocks.
M+D > MD = Pathology
If D1 is similimum to D, and ‘d’ is ‘molecular imprint’ of D1,
‘d’ will be complementary to D1 and D.
MD+d> M+Dd
M is free now (Cured)
Dd  is now bio-degraded or eliminated from the system.)
This is the proposed molecular mechanism involved in homeopathic therapeutics. This concept is logically and scientifically explained in this article in detail.
 Re-Building Homeopathy- A Historical Mission
Time has come for a meaningful dialogue regarding the scope for a scientific re-reading and revising of the fundamental principles and methods  of  Homeopathy. A radical re-building of  the whole system on a rational and scientific foundation is essential, emancipating this powerful therapeutic art from the clutches of unscientific, metaphysical and vitalistic ideologies. Modern physical sciences and technologies have evolved into such a state of maturity that we can now at least attempt with their help to provide a scientific and satisfactory explanation to the centuries-old mysteries and riddles associated with this wonderful therapeutic system. Such a fundamental re-building shall obviously help in enthroning homeopathy  on its rightful status of the most advanced branch of modern medical science, unfairly denied for more than last two hundred years.
I would like to entitle this emerging scientific version as DIALECTICAL HOMEOPAHY, since this reclaiming is essentially achieved utilizing the theoretical tools of dialectical methodology. DIALECTICAL HOMEOPATHY is basically an innovative and positive enhancement of classical Hahnemanian Homeopathy, and as such, may be considered as its ‘dialectical negation’ at large. Historically, it represents a qualitatively higher stage in the natural evolutionary growth and maturation of Homeopathy. ‘Dialectical’ also indicates its readiness to open up to new ideas, and engage in creative dialogue with other scientific disciplines. It advocates to discard all forms of dogmatism existing in homeopathy. Whereas ‘Homeopathy’ is the ‘seed’, ‘Dialectical Homeopathy’ is the emerging ‘seedling’- that much similar, that much different.
In this modern era of scientific enlightenment and technological advance, we can no longer hope to proceed further ahead with Homeopathy, without the help of a well proven and universally acceptable scientific methodology. We can no longer hope to depend merely upon certain set of somewhat mysterious quotations and philosophical speculations inherited from our great masters. It is very important that Homeopathy has to be first of all dealt with as a subject of science, not as a  religion or metaphysics. Essentially, the principles of  Homeopathy have yet to achieve the right to be recognized as part of modern medical science. To begin with, it has to attain acceptability among the modern scientific community, at least in terms of a rational  methodology and vocabulary.
Science is not a mere heap of lifeless and dry inflexible theories and dogmas. It is a live cognitive system, undergoing an endless process of self-renewal and growth. Science never celebrates the words of masters quoted out of context. It is the  the sum total of the ideas enwrapped in the expressed words that really matter. It is the readiness on its part to prove its propositions on practical level, to imbibe new  ideas, and to discard obsolete ones mercilessly, that makes science distinct from other intellectual activities. That is the touch-stone of scientific method. There is no water-tight compartments in the realm of science. Our approach to human knowledge should be dialectic, not dogmatic.
Human knowledge develops and unfolds itself through a never ending dialectic process of simultaneous assimilation and negation of history. It is impossible for anybody to proceed with his intellectual quest without drawing resources from the treasures of knowledge amassed by the by-gone generations. Obviously, no genius can totally overcome the objective limitations imposed upon him by the space-time context of his life and activities. Development of human knowledge should be percieved in relation with this  objective framework of  historical evolution. Man knows today much more than he knew yesterday.  Certainly he would know infinitely more tomorrow, than what he knows today. The knowledge of yesterdays, however great they might have been, were much incomplete than that of today. Tomorrow, human knowledge would be definitely more expansive and more comprehensive than that of today. The basis of scientific perspective of knowledge lies in realizing this fundamental truth.
We should never forget the objective historical context of 18th century Germany, where Samuel Hahnemann  lived and developed his novel therapeutic system. Two hundred and more eventful years have passed since it happened. It is not to be seen as a sin to say that his thoughts and propositions were definitely confined  by the  limitations imposed by the infantile level of science and technology then existed there. Even though the  the essence of the therapeutic principle he developed is capable of  transcending the boundaries of centuries to come, it would be unfair to try to evaluate his achievements and contributions detached from  his objective time-space framework.
Human knowledge has attained an ever greater maturity of more than two centuries, compared with the conditions that existed when Hahnemann lived. It is  an undisputable fact that man now knows much more about the diverse phenomena of this universe than in the era of Hahnemann. Hahnemann had developed his ideas depending upon the existing knowledge about the universe available to him. Naturally it is bound to  bear the   limitations imposed  by the objective historical and geographical context.
Obviously, modern science and its methodology were in its infancy in those days. Had he happened to live in this world 200 years later, the towering genius of Hahnemann would have presented to humanity a therapeutic system totally different, and much  more advanced and scientific than what we now call Homeopathy. He would have definitely rewritten completely what we preach and practice in the name of Homeopathy today.
All these facts underlines the crucial relevance of a  complete re-reading and reclaiming of the theory and practice of Homeopathy in conformity with modern scientific and historical context. Whenever we try to learn the teachings of Hahnemann,  we  should be on the look out to understand what he would have said about those subjects, if he were elaborating them in the modern context. We should not take his written words as if they were ultimates, unquestionable and beyond any scope of further revisions and improvements. We should honour the great master by following his teachings as valuable guide to tread forward, and not as lifeless dogmas.  This is the essence of dialectical methodology.
The theory and practice of Homeopathy has been always a matter of endless controversy, since its inception two hundred years ago. Representatives of the so-called ‘official science’ were always in a state of undeclared war against it. Rather than being hailed as a possible new medical breakthrough to give better  health for all, homeopathy has been ridiculed, ignored and systematically suppressed through centuries. We repeatedly hear about ‘successful” attempts by its opponents,  to ‘disprove’ it ‘scientifically’, and time and again declaring it a ‘fraud, placebo, or pseudoscience’. In spite of all these  scorns, ridicules and ‘witch hunts’, homeopathy still exists and thrives all over the continents, alleviating pain and sufferings of millions. The rising acceptance of homeopathy not only by the millions of lay public, but by the heads of states, members of royal families and many other dignitaries all over the world, has produced a state of dilemma in the world of medicine. Either all of these millions had fallen victims to a successful  global scale ‘medical hoax’, or the ‘learned scientists’  striving to disprove homeopathy, are being proved themselves wrong.
On the other side of the matter, certain unscientific and dogmatic concepts and notions still  dominate the mindset of many who work in the field of Homeopathy today. Many of them proudly claim that they are strict  followers of  Hahnemann,  and Hahnemann alone. We can meet ‘Classical Homeopaths’ who hesitate even to refer to any book other than those written by Dr. Hahnemann.  They raise questions about the ‘scientificness’ of modern science, and engage in ‘scholarly’ discourses regarding the futility of science and scientific method! They declare themselves to be practitioners of what they call ‘True Homeopathy’. They are not real followers, but only worshippers of Samuel Hahnemann. For them, Hahnemann is omnipotent and omniscient like a God! They will not tolerate any attempt of additions or deletions to what the master has said regarding homeopathy two hundred years back. According to them, homeopathy is the only ‘ultimate’  ‘scientific’ therapeutic system, and all other medical systems are absolutely ‘unscientific’. We also meet certain clever guys who try to sell homeopathy maximum through their own private outlets, by assigning attractive trade labels such as ‘predictive’, ‘true’, ‘pure’, ‘classical’, ‘expert’, ‘elite’ and so on.  Still another set of people ‘strive’ in vain to make homeopathy ‘competent’ to vie with modern medicine, by establishing commercial corporate networks of high-tech ‘super speciality  clinics’, pretending themselves to be Homeo Pediatricians,  Homeo Psychologists, Homeo Gynecologists and many other specialities. Are not those people trying to fool the public and themselves by enacting such absurd drama, whereas it is well known that, being a holistic system of therapeutics, there is very limited scope for such specialities in Homeopathy.  Recently, I have even had a chance to interact with an ‘elite class’ young homeopath, declaring himself to be a follower of a new ‘predictive’ school in homeopathy, exclaiming that the theory of ‘similia similibus curentur’ is outdated, and he no longer requires any Repertory or Materia Medica to practice his ‘scientific’ brand of homeopathy! Making the scenario still worse and hopeless, all sorts of unscientific and unethical commercial patented formulations are flooding the market, in the guise of “Scientific Homeopathy”. The  irony is that all these people of various colors and clowns are claiming themselves to be the  only ‘true’ disciples of a great Genius, who displayed the intellectual courage to  reform and re-write  his own ‘Organon of Medicine’  six times in his life time, as part of his unrelenting quest for truth and perfection. As this undeniable historical truth remains, it is a pity to note that people who claim themselves to be the ardent followers of the great Master, are shutting their doors on the face of all new knowledge and  scientific enlightenment with such hideous tenacity.
 The Parallel Road Pursued by Hahnemann
 Samuel Hahnemann, the great founder of Homeopathy,  was born on 10th April 1755 in Germany. He died on 2nd July 1843. ‘Similia Similibus Curentur’ or ‘Likes Cures Like’ is the expression of a universally applicable natural therapeutic law revealed to him as a result of his extraordinary observational skills and ardent study. Based on this fundamental law of natural curative process hitherto unknown to humanity, Hahnemann laid the foundation for a  new therapeutic system called homeopathy. A detailed theoretical frame work and practical tools for this new system of therapeutics were also developed during his later years. It is the aim of this article to re-read and re-evaluate these principles in the light of modern biochemistry and other bio-physical sciences. Such a rational re-reading is expected to culminate in  providing a scientific explanation for the fundamental principles of homeopathy at large.
The epoch-making revelation of Hahnemann regarding the fundamental law of cure was of so much relevance and implications that it really deserved to be recognized in the history of human knowledge along with Newton’s Theory  of Motion, Theory of Gravitation, or Darwin’s Theory of Evolution. It was a grave unpardonable historical blunder on the part of contemporary scientific world that such a recognition did not happen. Had it been possible for them to imbibe Hahnemann’s findings in its real gravity, the fate and course of modern medicine would have been entirely different.
Physical Sciences of 18th Century Germany was in its early infancy, and obviously, could not recognize the importance of the new therapeutic law discovered by Samuel Hahnemann. The toolbox of contemporary science and technology was not sufficiently equipped to address this task. Mindset of of the leading personalities working in diverse disciplines of  physical sciences were  governed by the world outlook of mechanistic materialism. Naturally, they could not  take up the task of assimilating  Hahnemann’s findings and propositions, which presented much more complicated theoretical and practical issues that were beyond the boundaries of their mechanistic methodologies. This situation resulted in some sort of willful neglect and apathy from the part of mainstream scientific community towards Hahnemann and his discoveries. They miserably failed to comprehend the revolutionary content and epoch-making relevance of Hahnemann’s findings. Hahnemann, whose apathy towards the contemporary medical system and its professional community is well known, may also have chosen to keep himself aloof from mainstream science. His unrelenting ideological rebellion against the influence of mechanical materialism existing in the dominant medical stream may have led him inevitably into some sort of metaphysical and idealistic  philosophical gleanings, which  dominated the contemporary non-scientific intellectual arenas. Inevitably, homeopathy was constrained to follow an independent parallel intellectual course, far removed from the mainstream science. Hence it is not really unexpected that homeopathy is reveling in an atmosphere much akin to speculatory theorizations, rather than an objective scientific activity. Even today, homeopathy is not able to free itself from the clutches of the above mentioned parallel path. Still it has not come to terms with modern mainstream Science.
As a simple and effective therapeutic system, free of any fear of unwanted side effects,  homeopathy has already gained acceptability to a great extent during the by gone two centuries. The principle of ‘Similia Similibus  Curenter’ has sufficiently proved its ‘right of existence’ through thousands and thousands of miraculous cures by homeopaths all over the world. But we cannot overlook the fact that we have not yet succeeded in explaining this principle scientifically enough. Modern physical sciences and molecular biology have accumulated a huge wealth of knowledge in recent years, unraveling even the minutest secrets of the phenomenon of life . But we have not yet been able to recreate the fundamental principles of homeopathy scientifically and convincingly enough, by taking advantage of the above mentioned modern scientific achievements. Homeopathy shall be duly recognized and respected as an advanced branch of modern molecular medicine, only when such a scientific recreation of its basic premises is attained. Until  then, acceptance of our claim that homeopathy is a science will remain confined  to ourselves alone.
Material Basis of Vital Processes
Modern Science has already unraveled many fundamental facts regarding the ‘chemistry of life’, crucial in exploring the secrets of the biological phenomena of life, health, illness, cure and death. To take up the task of providing scientific explanations to the theory of ‘Similia Similibus Curentur’, it is imperative that we should be well equipped with a clear understanding about these  fundamental facts.
By the term ‘living organism’, we indicate a material system with a specific  quantity, quality, structure and functions of its own, which is capable of self-controlled growth and reproduction of its progeny, by accepting matter and energy from its environment. The phenomenon of life exists through a continuous chain of highly complex biochemical interactions which control each other, depend up on each other and are determined by each other. A ‘living organism’ represents a much higher and advanced level of existence of the same elements of matter we meet in the inorganic world,  different only in its structural organization and functional complexity. The universal phenomenon of material motion we find as part of primary existence of matter itself, attains the wonderful qualities of life, due to this complex structural organization. In fact, ‘life’ is the result of a continuous evolutionary process of primary matter in this universe through millions of years, attaining different levels of organizational and functional forms. Primary forces, sub-atomic particles, elementary atoms, simple chemical  molecules, complex inorganic molecules, carbon containing organic molecules, bio-molecules, complex bio-polymers, RNA-DNA-Protein structures, organelles, unicellular organisms, multi-cellular organisms, diverse species of plants and animals, and ultimately Homo Sapiens- these are the prominent milestones in the known evolutionary ladder on earth, panning through millions and millions of years. Human beings represents the highest form of this material evolutionary history on earth, as far as it is known to us. Parallel to this biological evolution, we can perceive a systematic evolution and perfection of the nervous system also. Simple forms of conditioned reflexes that existed in primitive organisms, gradually evolved into nerve cells, neural networks and ultimately into a well organized nervous system in higher animals. In higher forms of life such as humans, this nervous system has attained such a structural and functional perfection that human brain and its diverse faculties have begun playing a decisive role even in the existence and development of that species and even life on earth itself. Of course, collective labor, language and social relations also played a major role in this evolutionary process.
A living organism can exist only through a continuous interaction with its environment. There is an unceasing flow of matter and energy in both directions,  between internal and external environments of the organism. Metabolism, or ‘life process’ is the term used to describe the sum total of this flow. The moment this bi-directional flow of matter and energy ceases, the organism can no longer exist.
 Chemistry of Life
 A living organism is distinguished from other non-living forms of matter by certain fundamental features such as: high level of structural organization, the ability to convert and utilize energy, continuous material exchange with environment, self regulation of chemical transformations, and,  reproduction or transfer of hereditary information. A state of disease may ensue when any of the bio-chemic channels governing these fundamental factors of life are disturbed.  Obviously, it is impossible to make a scientific study of pathology and therapeutics without an understanding of these subjects.
Complex bio-molecules which participate in the diverse chemical processes of life are broadly classified into four major groups: Proteins, Carbohydrates, Lipids and Nucleic Acids. These are polymers of simple chemical components or sub units, called monomers. The monomers of proteins are amino acids, and those of carbohydrates are  monosaccharides. Lipids are polymers of fatty  acids. The monomers of Nucleic acids are known as nulcleotides. These bio-molecules are considered to be the building blocks of life on earth, and are never seen in the non-living world. These bio-molecules, with their highly complex structure and organization, interact each other in the organism through hundreds of bio-chemic pathways, collectively called ‘vital processes’.
Importance of Proteins and Enzymes
 We cannot engage in a meaningful discourse regarding the phenomena of life and disease without a proper understanding of the protein and enzyme chemistry, and the complex dynamics of their molecular interactions.  Proteins are a class of highly complex nitrogen-containing bio-molecules, functioning as the primary carriers of all the bio-chemic processes underlying the phenomenon of life.  There exist millions of protein molecules belonging to thousands of protein types in a living organism. Each protein molecule is formed by the polymerization of monomers called amino acids, in different proportions and sequences. Each protein type has its own specific role in the bio-chemic interactions in an organism. Most of the amino acids necessary for the synthesis of proteins are themselves synthesized from their molecular precursers inside the body.  A few types of  amino acids cannot be synthesized inside the body, and have to be made available through food. These are called essential aminoacids. There are specific protein molecules assigned for each bio-chemic process that take place in the body. Various proteins play different types of roles, like biological catalysts or  enzymes, molecular receptors, transport molecules, hormones  and antibodies. Some proteins function as specialized molecular switches, systematically switching on and off of specific bio-chemic pathways. Proteins are synthesized from amino acids, in conformity with the neucleotide sequences of concerned genes, with the help of enzymes, which are themselves proteins. ‘Protein synthesis’ and ‘genetic expression’ are very important part of vital process. It  may be said that genes are molecular moulds for synthesizing proteins. There are specific genes, bearing appropriate molecular codes of information necessary for synthesizing  each type of protein molecule. Even the synthesis of these genes happens with the help of various enzymes, which are protein molecules. There is no any single bio-molecular process in the living organism, which does not require an active participation of a protein molecule of any kind.
The most important factor we have to understand while discussing proteins is the role of their three-dimensional spacial organization evolving from peculiar di-sulphide bonds and hydrogen bonds. Water plays a vital role in maintaining the three dimensional organization of proteins intact, thereby keeping them efficient to participate in the diverse biochemical processes.  Proteins exhibits different levels of molecular organization: primary, secondary, tertiary  and quaternary. It is this peculiar three dimensional structure that decides the specific bio-chemic role of a given protein molecule. More over, co-enzymes and co-factors such as metal ions and vitamins play an important role in keeping up this three-dimensional structure of protein molecules  intact, thereby activating them for their specific functions.
Whenever any kind of error occurs in the particular three-dimensional  structure of a given protein molecule, it obviously fails to interact with other bio-molecules to accomplish the specific functions it is intended to play in the concerned bio-chemic processes. Such a failure leads to harmful deviations in several bio-chemic processes in the organism, that require the participation of this particular protein, ultimately resulting in a cascading of multitude of molecular errors. This is the fundamental molecular mechanism of pathology, which we perceive as disease of some or other category.  These deviations in bio-chemic pathways are expressed as various groups of subjective and objective symptoms of disease. The organic system exhibits a certain degree of ability and flexibility to overcome or self repair such molecular deviations and preserve the state of homeostasis required to maintain life. Anyhow, if these deviations happen in any of the vitally decisive bio-chemic pathways, or, if these are beyond self repair, the bio-chemic processes ultimately stop and death happens.
Broadly speaking, the molecular errors which underlie diverse conditions of pathology belong to any of the following types:
1. Nutritional  deficiencies of amino acids: Any shortage in the availability of various amino acids and their precursers may lead to non- production of proteins in the organism. In some cases, it may result in the production of defective proteins.
2. The absence or defects of appropriate genetic materials, coding the information required for the production of various protein molecules utilizing amino acids, may inevitably lead to total failure of protein synthesis, or to production of defective proteins. These come under the class of genetic proteinopathies.
3. The deficiencies or errors related with the enzymes required for genetic expression in the process of protein synthesis and post-translational transitions may lead to non production of essential proteins, or may lead to production of defective proteins.
4. Any deficiencies or structural defects of co–factors and  co-enzymes                which help the protein molecules maintain their specific three-dimensional structure and activate them. This may be due to the nutritional deficiencies of essential elements and vitamins, or due to some errors in their metabolic pathways.
5. The absence of congenial physiologic conditions for protein molecules to remain active. Dehydrations, deviations of  pH in the internal medium, variations of temperature, harmful radiations etc. may deactivate the protein molecules.
6. The absence or structural defects of certain substrate molecules which are to interact  with proteins in bio-chemic processes.
7. The inability of substrates to interact with protein molecules due to binding of any foreign molecules or ions on themselves.
8. Molecular inhibitions of protein molecules, resulting from  binding with exogenic or endogenic foreign molecules or ions, including metabolites.
It is obvious that almost all conditions of pathology we normally confront, including those resulting from genetic origin, are involved with some or other errors or absence of some protein molecules that are essential for concerned bio-chemic processes. Moreover, most of such molecular errors other than of genetic origin, arise due to binding of some exogenic or endogenic foreign molecules or ions on the active, binding or allosteric sites of protein molecules, effecting changes in the three-dimensional configurations of protein molecules. A host of diseases originating from viral-bacterial infections, allergies, poisoning, drugs, food articles etc, belong to this category.
The most important factor we have to bear in mind when talking about kinetics of proteins in general, and  enzymes in particular is their highly defined, peculiar specificity. Each type of protein molecules,  or some times even some part of a single protein molecule, is designed in such a way that it can bind only with a specific class of molecules, and hence participate in a specific type of bio-chemic interaction only. This functional specificity is ensured through the peculiar three-dimensional configuration of the protein molecules, exhibited through their characteristic folding and spacial arrangement. Reactive chemical groups known as active sites, binding sites, and regulatory sites are distributed at specific locations on this three dimensional formations of protein molecules. These chemical groups can interact only with molecules and ions having appropriate spacial configurations that fits to their shape. This phenomenon can be compared with the relationship existing between a lock and its appropriate key. Just as a key with an exactly fitting three dimensional shape alone can enter the key hole of a lock and open it,  molecules with exactly fitting three dimensional structure alone can establish contact and indulge in chemical activities with specific protein molecules. This key-lock relationship with substrates defines  all biochemical interactions involving proteins, ensuring their optimum specificity. Obviously, any deviation in the three dimensional configuration of either lock or key makes their interaction impossible.
It has  been already explained that the primary basis of any state of pathology is some deviations occurring in the biochemical processes at the molecular level. Endogenic or exogenic foreign molecules or ions having any configurational similarity to certain biochemical substrates can mimic as original substrates to attach themselves on the regulatory or the active sites of proteins, effecting changes in their native    3-D configuration, thereby making them unable to discharge their specific biochemical role. This situation is called a molecular inhibition, which leads to pathological molecular errors. It is comparable with the ability of objects having some similarity in shape with that of key, to enter the key hole of a lock and obstructing its function. As a result of this inhibition, the real substrates are prevented from interacting with the appropriate protein molecules, leading to a break in the normal biochemical channels. This type of molecular errors are called competitive inhibitions. It is in this way that many types of drugs, pesticides and poisons interfere in the biochemical processes, creating pathologic situations. Such substances are known as anti-melabolities.

Post a Comment