A catalyst is a substance that enters into the process of a reaction. It might undergo temporary change in the molecular structure, but ultimately the catalyst molecule is restored to its original structure before the product has been formed. Catalysts generally reduce the Energy of Activation so that product might be formed at a lower temperature. (Fig 1)
Figure 1
In some cases, if it weren't for the catalyst, the reaction would occur so slowly that practical product formation would not be feasible. From a molecular point of view the catalyst provides a surface for the reactant molecules to position themselves with one another so that when they do collide they will do so much more effectively. There are two kinds of catalysts:
Heterogeneous catalysts
Homogeneous catalysts
Heterogeneous Catalysts
Heterogeneous catalysts are sometimes called surface catalysts because they position the reactant molecules on their very surface. Many metals serve as heterogeneous catalysts in which the reactant molecules have an interface between themselves and the catalyst surface. In the reaction known as Hydrogenation, double bonds between carbons accept two hydrogen atoms and use the Pi electrons between the two carbons in order to attach these hydrogen atoms to the carbon atom. The di-atomic Hydrogen molecule attaches itself to the surface of a metal catalyst such as Platinum, Nickel, or Paladium. The double bonded organic molecule does the same. The single bond between the Hydrogen atoms is broken, and so is the Pi bond between the two carbons within the organic molecule broken. The Hydrogen atoms then form a single bond with its single electron and one of the two Pi electrons that previously constituted the Pi bond between the two carbon atoms. Once the Hydrogens have been attached the product molecule disengages from the surface only to have fresh reactant molecules take its place upon the surface of the metal. Heterogeneous catalysts are, as a rule, not as efficient as homogeneous catalysts.
Homogeneous Catalysts
Homogeneous catalysts are catalysts that form a uniform distribution between themselves and the reactant molecules. These catalysts are in a solution along with the reactant molecules. Because they are dispersed within a solution, the surface area of the catalyst is maximized, and usually, these types of catalysts tend to be more efficient in increasing product formation at a lower temperature. Examples of homogeneous catalysts would include any protic acid. A protic acid would be an acid that donates Hydrogen ions(protons). Sulfuric Acid, H2SO4, in water catalyze dehydrations of alcohols (ie:loss of water) to produce double bonded compounds called alkenes. Phosphoric Acid, H3PO4, can catalyze the formation of organic esters by the combining of an alcohol and a carboxylic acid molecules together splitting out a water molecule from between the two molecules.
Aprotic acids also serve as homogeneous catalysts. An aprotic acid is an acid that accepts electrons. It is called a Lewis acid. Aprotic acids such as AlCl3 can catalyze the substitution reactions in which a hydrogen atom on a Benzene ring is replaced by a hydrocarbon group such as a methyl group,-CH3. This same aprotic acid is also useful in catalyzing the Chlorination of an alkene to form a di-chloro alkane.
Probably the most amazing and incredably efficient homogeneous catalysts are the proteins that make up the enzymes. Enzymes are biochemical catalysts with an amazing efficiency far outstripping the other homogeneous and heterogeneous catalysts. One enzyme may be responsible for catalyzing the formation of 1000-10,000 or up to as many as one million product molecules. Reaction rates can increase by 108 to 1011 times faster than the uncatalyzed reaction. In addition, enzymes have an uncanny specificity in that it is rare for a specific enzyme to catalyze more than one specific reaction.
How do enzymes catalyze a reaction? Lock and Key Model of Enzyme Activity Enzymes are made up of a protein part called the apoenzyme and a non-protein part called the Prosthetic group. There is a model that seeks to explain how enzymes function with such a high degree of efficiency and specificity. The earliest model was called the "lock and key" model of enzyme activity. In this model the apoenzyme has one or more cavities on the surface of this macro-molecular system which can bind a reactant molecule called a substrate to the cavity. This cavity or indentation is called the "active site". According to this model, once the substrate molecule has been positioned with the help of the prostetic group and perhaps a Co-factor metal ion, then the bond breaking and bond formation can begin. Once the product has been formed, the product disengages from the active site in order for the process to be repeated. According to this model, the shape of the substrate molecule must be compatible to the active site like a key is compatible with a specific lock. This would explain the unusual high specificity of enzymes capable of only catalyzing one reaction. If the wrong substrate tries to fit into the active site, it does not fit (wrong key) and so the enzyme does not catalyze its conversion to some other product. If the active site of the enzyme is stretched or compressed then even the real substrate molecule will not fit the distorted active site. The problem with this model is that it does not explain why some bogus substrate molecules can "fool" the enzyme into thinking the bogus is the real thing. The bogus molecule fits into the active site even though it is not the exact same size as the real thing. Once the bogus molecule is in place it just sits there and blocks the active site. This inhibits the enzyme from doing its job and is referred to as active site blocking.
Induced Fit Model (or Hand and Glove) of Enzyme Activity The Induced Fit model is a modification of the lock and key model. Instead of having a ridged substrate molecule that will only fit into a specific active site, we have an active site that can stretch to accept a range of molecular shapes for the substrate analogous to how gloves stretch to fit more than one size hand. This model explains more adequately how active site blockers can block the active site and inhibit the enzyme molecule.
Types of Enzyme Inhibitors There are really two types of inhibitors: Competitive Inhibitors- These are molecules that actually block the active sites and "compete" for the locked position of the active site. Non-competitive Inhibitors- These are molecules that attach themselves to other parts of the apoenzyme away from the active site. However, when the inhibitor bonds to the enzyme molecule, it alters the shape, and therefore, the shape of the active site is altered so that the active site will no longer accept a legitimate substrate molecule. Factors Affecting The Enzyme Activity There are three factors that will alter the activity of an enzyme. Temperature- Every enzyme has a temperature range in which the enzyme can function within. Usually on the low end of that range the enzyme has low activity.Near the middle part of the range, the activity of the enzyme increases to a maximum called the optimum temperature. Outside that range, the enzyme ceases to function as a catalyst. The temperature range of most of the hundreds of enzymes found in the human organism is 10-50 degrees Celsius with the optimum temperature being 37 C. If a human becomes hypothermic with a abnormally low body temperature, then enzymes cease to function and biochemical reactions within the cells begin to shut down. If the human becomes hyperthermic with an abnormally high body temperature, then the enzymes activity drops rapidly, and the reactions of the cells begin to shut down once again. If the body temperature gets too far away from the optimum temperature, then the body may cease to function. At what temperature this occurs really depends upon the individual. Every individual has there own tolerances of temperature variation. What we do is usually deal with a statistical average which is really non-existent, but takes in most individuals. When the body experiences extremes in temperature, then the body usually begins shutting down non-essential systems to life support and the individual goes into a coma. Coming out of a coma usually depends but not always on correcting the temperature extreme. High temperatures usually inhibit enzyme activity by denaturing the protein enzyme. The temperature will cause the protein shape to be so distorted that the active site is distorted to the point that the substarte is no longer accepted.
Acidity- Every enzyme functions within a pH range with an optimal pH within that range. Enzymes are extremely sensitive to pH changes so their ranges tend to be rather narrow. For example, the enzymes that catalyze blood chemistry must function within a tiny range of 7.35-7.45 in plasma. If the pH drops outside that range on the low end then a condition known as acidosis occurs and enzymes cease to function and the blood chemistry shuts down. On the other hand if the pH goes outside that 0.1 pH range on the high side, we have a condition known as alkalosis. If this should happen the structure and shape of the enzyme is altered so drastically that the active sites no longer can accept the substarte molecules because of their distortion. Changing the pH disrupts intramolecular binding forces that keep the enzyme in a specific shape. Disrupting those forces will unravel the protein and render the active site distorted. Active site blocking- We have already discussed how competitive inhibitors can affect the enzyme activity. Toxicology and Enzyme Inhibition Toxicolgy is the study of toxic agents. Toxic agents is a little disceptive. Most people think of something that is toxic as something that will cause certain death. This is not always the case. Toxicity depends on a number of factors. The body weight of the organism has to be considered. The tolerance level of the toxin in the organism is a factor. The dosage of toxin ingested and the time interval of the ingestion all have to be considered as important to gauge just how toxic a toxin is. To use a ridiculous hyperbole, one can die of too much water due to kidney shutdown, but we would not think of calling water a toxin. Depending on the dosage and body weight some toxins only nausiate whereas others cause vomiting, convulsions, coma, and, yes, even death.
How do toxins work? Some toxins such as heavy metals like Mercury,Lead, and other transition metals will denature enzymes causing them to be precipitated along with the metal. In many of these toxins the antidote is to ingest something that will precipitae the metals like , in some cases, drinking milk where the protein in the milk casein will precipitate the metals and allow them to be vomited or passed out of the body in some way. Other toxins function as active site blockers inhibiting an enzyme from catalyzing a necessary biochemical reaction. For example, Cyanide is a toxin which will block the active sites of some enzymes called cytochomases that are responsible for cellular respiration. When these enzymes are blocked by the cyanide then cells die of asphixiation. Many insecticides and pesticides work on the principle of blocking the active sites of enzymes within an insect or plant that affect the growth of the organism or the central nervous system of the organism shutting it down. The problem with many such pesticides and herbacides is that they can easily be harmful to humans if ingested through the mouth, nose or in some cases the pores of the skin. There are a group of toxins called neurotoxins that affect the neuromuscular system. These substance block the active site of an important enzyme of the neuromuscular system called acetylcholine esterase. This enzyme is responsible for hydrolyzing acetyl choline as an ester after it was produced in order to initiate muscular contraction. The problem is that if the resulting acetylcholine molecule is not converted back to choline with the aid of the acetylcholine esterase, then muscles cannot return to a relaxed state which could result in paralysis of the heart beat, respiration and other processes controlled involuntarily by the neuromuscular system. Massive doses of neurotoxins will result in the respiratory system, the nuromuscular system and the cardiovascular systems being paralyzed and death occuring rapidly. Enzyme Inhibition And Chemotherapy Lest I leave you with the impression that all enzyme inhibition results in bad things happening, let me cite successes in chemotheraputic treatment of cancer. It was shown earily in this research that an organic base derivative 5-fluro uracil was responsible for arresting the growth of cancer cells by inhibiting an enzyme responsible for synthesizing the DNA of cancer cells. There are many problems with such agents in that in far too many cases the same agent that kills cancer cells will indiscriminately kill normal cells as well. However, research is proceeding in developing support medicines that will control the negative side effects in using such chemotherapeutic agents such as nausia, loss of hair,skin lessons, and loss of apetite. In addition, new drugs are being developed that are more discriminating on killing the cancer cells leaving the normal cells intact. In addition, certain muscle relaxants such as succinylcholine act as a substitute for acetylcholine in binding to muscle receptor sites. Succinylcholine causes muscle relaxation instead of contraction and since the acetylcholine esterase can't hydrolyze the Succinylcholine as efficiently as acetylcholine, the muscle remains in a relaxed state longer.
Stanford Moore was born in 1913 in Chicago, Illinois, and grew up in Nashville, Tennessee, where his father was a member of the faculty of the School of Law of Vanderbilt University. His developmental years were in a home environment which made the pursuit of knowledge an eagerly adopted undertaking. He had the opportunity to attend a high school administered by the George Peabody College for Teachers in Nashville. A skilled teacher of science, R.O. Beauchamp, kindled an interest in chemistry. Moore entered Vanderbilt University undecided between a career in chemistry or aeronautical engineering. The courses which he took in the engineering school presaged a concern for instrumentation. But a gifted professor of organic chemistry, Arthur Ingersoll, succeeded in presenting the study of molecular architecture as an even more appealing discipline. Moore graduated from Vanderbilt (B.A. 1935, summa cum laude ) with a major in chemistry. The faculty recommended him for a Wisconsin Alumni Research Foundation Fellowship which took him to the University of Wisconsin where he received his Ph.D. in organic chemistry in 1938.
His thesis research was in biochemistry in the laboratory of Karl Paul Link. The first lessons that the young graduate student received from the skilled hands of his professor were in the microanalytical methods of Pregl for the determination of C, H, and N; Link had recently returned from Europe where he had studied in the laboratory of Fritz Pregl in Graz. This training from Link in microchemistry was especially valuable for a student who was later to be concerned with the quantitative analysis of proteins. Moore's thesis was on the characterization of carbohydrates as benzimidazole derivatives. The experience of bringing that work from the bench to the printed page under Link's guidance marked Moore's transition from a student to a productive scholar.
Karl Paul Link was a friend of Max Bergmann, who had recently arrived from Germany to lead a laboratory at the Rockefeller Institute for Medical Research in New York. Through that friendship, Moore was encouraged to join the Bergmann Laboratory in 1939, which was an internationally renowned center of research on the chemistry of proteins and enzymes. During Emil Fischer's last years Max Bergmann had been his senior research associate, and Bergmann had attracted to Rockefeller a group of versatile chemists who maintained a tradition of innovative research and high productivity. After nearly three valuable years in such company, which included William H. Stein, the advent of World War II drew Moore out of the laboratory to serve as a junior administrative officer in Washington for academic and industrial chemical projects administered by the Office of Scientific Research Development. At the close of the war, he was on duty with the Operational Research Section attached to the Headquarters of the United States Armed Forces in the Pacific Ocean Area, Hawaii.
During the war years, the situation at the Rockefeller Institute had changed. The untimely death of Max Bergmann in 1944 had brought to a close the major chapter in biochemistry which the contributions of his laboratory comprised. Moore's decision to return to Rockefeller was influenced by Herbert Gasser, then the Director of The Rockefeller Institute, who offered to give modest space to Moore and Stein to pursue the theme of research which they had begun with Bergmann or any new lines of investigation that appealed to them. Thus began the collaboration that led to the development of quantitative chromatographic methods for amino acid analysis, their automation, and the utilization of such techniques, in cooperation with younger associates, in the researches in protein chemistry summarized in the Nobel Lecture by Moore and Stein.
The investigations were conducted in an atmosphere at Rockefeller that encouraged interdepartmental cooperation and international consultation that would expedite research. Interludes included Moore's tenure of the Francqui Chair at the University of Brussels in 1950, where, at the generous invitation of E.J. Bigwood, a laboratory of amino acid analysis was organized in the School of Medicine. Moore had the opportunity to round out the year in Europe with six months in England at the University of Cambridge where he shared part of a laboratory with Frederick Sanger during the time of the pioneering studies on insulin. In 1968, Moore was a Visiting Professor of Health Sciences at the Vanderbilt University School of Medicine.
Memberships and Activities
American Society of Biological Chemists (Treasurer, 1956-59; Editorial Board, 1950-60; President, 1966), American Chemical Society, hon. member Belgian Biochemical Society, foreign correspondent Belgian Royal Academy of Medicine, Biochemical Society (Great Britain), U.S. National Academy of Sciences (Chairman, Section of Biochemistry, 1970), American Academy of Arts and Sciences, Harvey Society, Chairman of Panel on Proteins of the Committee on Growth of the National Research Council (1947-49), Secretary of the Commission on Proteins of the International Union of Pure and Applied Chemistry (1953-57), Chairman of the Organizing Committee for the Sixth International Congress of Biochemistry (1964), President of the Federation of American Societies for Experimental Biology (1970).
Honors
Docteur honoris causa from the Faculty of Medicine of the University of Brussels (1954) and from the University of Paris (1964). Award shared with William H. Stein: American Chemical Society Award in Chromatography and Electrophoresis, 1964; Richards Medal of the American Chemical Society, 1972; Linderstrom-Lang Medal, Copenhagen, 1972. I was born June 25, 1911 in New York City, the second of three children, to Freed M. and Beatrice Borg Stein. My father was a business man who was greatly interested in communal affairs, particularly those dealing with health, and he retired quite early in life in order to devote his full time to such matters as the New York Tuberculosis and Health Association, Montefiore Hospital and others. My mother, too, was greatly interested in communal affairs and devoted most of her life to bettering the lot of the children of New York City. During my childhood, I received much encouragement from both of my parents to enter into medicine or a fundamental science.
My early education was at the Lincoln School of Teachers College of Columbia University in New York City, a school which was considered progressive for that time and which fostered in me an active interest in creative arts, music, and writing. There I had my first course in chemistry which proved to be an extremely valuable and interesting one. I left this school when I was about sixteen and went to an excellent preparatory school in New England, namely Phillips Exeter Academy, which was at the time, although it has changed since, a much more rigid and much more demanding educational experience than I had had at Lincoln. It was at Exeter that I was introduced to standards of precision of writing, and of work generally which I think has stood me in very good stead, and I believe that the combination of a progressive school and a more demanding school such as I enjoyed was an ideal preparation. From Exeter I went to Harvard where I had a very enjoyable, although not a very academically distinguished career, and graduated from the college in 1933 at the depths of the economic depression. I had majored in chemistry at college and decided to continue on at Harvard as a graduate student in that subject. This proved to be a rather unfortunate experience because my first graduate year was undistinguished, to say the very least. I was almost ready to abandon a career in science when it was suggested to me that I might enjoy biochemistry much more than straight organic chemistry.
The next year, I transferred to the Department of Biochemistry, then headed by the late Hans Clarke at the College of Physicians and Surgeons, Columbia University in New York. The department at Columbia was an eye-opener for me. Professor Clarke had succeeded in surrounding himself with a fascinating and active faculty and an almost equally stimulating group of graduate students. From both of these I learned a tremendous amount in a short time. My thesis involved the amino acid analysis of the protein elastin, which was then thought to play a role in coronary artery disease and I completed the requirements for my degree at Columbia late in 1937 and went directly to the laboratory of Max Bergmann at the Rockefeller Institute.
While still a graduate student, I had the extreme good fortune to marry, in 1936, Phoebe Hockstader who has been of enormous support to me ever since. We have three sons, William H. Jr., 35; David F., 33; Robert J., 28.
Bergmann was, I still feel, one of the very great protein chemists of this century and he, too, had the ability to surround himself with a most talented group of postdoctoral colleagues. In the laboratory at the time that I was there were, of course, Dr. Moore, and, in addition, Dr Joseph S. Fruton, Dr Emil L. Smith, Dr. Klaus Hofmann, Dr. Paul Zamecnik, and many others. It was impossible not to learn a great deal about the business of research in protein chemistry from Bergmann, himself, and from the outstanding group he had around him.
The task of Moore and myself was to devise accurate analytical methods for the determination of the amino acid composition of proteins, because Bergmann firmly believed, as did we, that the amino acid analysis of proteins bore the same relationship to these macromolecules that elementary analysis bore to the chemistry of simpler organic substances. It was during this period in the mid-thirties that Bergmann and Fruton and their colleagues were working out the specificity of proteolytic enzymes, work which has had a profound effect upon our knowledge of how enzymes function and has made it possible to use these proteolytic enzymes as tools for the degradation and subsequent derivation of structure of protein molecules ever since.
Work on proteins was suspended during the war for other more pressing matters and Dr. Moore left the laboratory in order to be of assistance in Washington and elsewhere. Our entire group was engaged in working for the Office of Scientific Research and Development. Bergmann's death in 1944 robbed the world of a distinguished chemist and, of course, left the laboratory without a chief. The group continued to function until the end of the war at which time Moore and I had the very great good fortune to be asked by Dr. Herbert Gasser, Director of the Institute, to stay on at Rockefeller with the freedom to do anything we pleased in the biochemical field.
In the meantime, had come the remarkable developments in England on the separation of amino acids by paper chromatography by Martin and Synge and Sanger had started his classical work on the derivation of the structure of insulin. It was then, perhaps, not surprising that Moore and I resumed our collaboration, and following a suggestion of Synge began to try to separate amino acids on columns of potato starch. We were very fortunate in hitting upon a type of potato starch which was well-suited to our needs almost immediately, and from that day on began to work first on the amino acid analysis, and then on the structural analysis of proteins. From columns of potato starch, we progressed to columns of ion exchange resins, developed the automatic amino acid analyzer, and together with a group of very devoted and extremely skillful collaborators, began work on the structure of ribonuclease. These columns were also used for other purposes. In the course of the early work, we developed a drop-counting automatic fraction collector which is now a common instrument in most biochemical laboratories throughout the world.
I should like to emphasize that the development of methods grew out of a need rather than a particular desire to develop methods as ends in themselves. We needed to know the amino acid composition of proteins, we needed to be able to separate and analyze peptides in good yield, and we needed to be able to purify proteins chromatographically. Since there were no methods for doing any of these things at the time that we started, we had to devise them ourselves. We not only wanted to know what the amino acid sequence of an enzyme such as ribonuclease was, but we tried to find out as much as we could about what made it an enzyme and after we had taken that particular enzyme about as far as we thought we could profitably go, we turned to a number of others which have been listed in the Nobel Lecture.
During all of this time, we had the undeviating support of an enlightened administration at Rockefeller who believed in allowing us to do those things which we thought to be important, and, during the last years of this work, we also have had great financial assistance from the NIH. For this and particularly for the very large number of devoted and talented colleagues which we have had in the laboratory we shall be forever grateful.
During all of this time, each of us, naturally, developed interests outside of the laboratory. I, for example, became greatly concerned about the promulgation of scientific information and have been attached, in one way or another, to the Journal of Biological Chemistry for a matter of over fifteen years. During this time it has been my privilege to work with a knowledgeable and dedicated group of biochemists who have devoted themselves unselfishly to serving the interests of their fellow biochemists throughout the world.
Scientific Societies - National Academy of Sciences, American Academy of Arts and Sciences, American Society of Biological Chemists, Biochemical Society of London, American Chemical Society, American Association for the Advancement of Science, Harvey Society of New York.
I was a member of the Editorial Committee of the Journal of Biological Chemistry, which is an elective office, for six years and Chairman of this Committee for three, 1958-61. After the conclusion of my work on the Editorial Committee, I became a member of the Editorial Board of the Journal of Biological Chemistry in 1962, and then an Associate Editor from 1964 until 1968. I assumed the Editorship, succeeding John T. Edsall, in 1968, a post I was forced to relinquish by illness in 1971.
Other Activities - Member of the Council of the Institute of Neurological Diseases and Blindness of the NIH, 1961-66; Chairman of the U.S. National Committee for Biochemistry, 1968-69; Philip Schaffer Lecturer at Washington University at St. Louis, 1965; Harvey Lecturer, 1956; Phillips Lecturer at Haverford College, 1962; Visiting Professor at the University of Chicago, 1961; Visiting Professor at Harvard University, 1964; Member of Medical Advisory Board, Hebrew University-Hadassah Medical School, 1957-1970; Trustee, Montefiore Hospital.
Awards (shared with Stanford Moore): American Chemical Society Award in Chromatography and Electrophoresis, 1964; Richards Medal of the American Chemical Society, 1972; Kaj Linderstr?m-Lang Award, Copenhagen, 1972.
|
|
| free web hits counter |
This is my BrainyGoose:
United States, IL, Chicago, English, Italian, Genry, Male, 21-25, bodybulding, swiming.