Enzymes And Enzyme Activity

Enzymes are the substances that allow life to exist at earth temperatures. Without such substances most chemical reactions that maintain a viable organism would not occur below 90 degrees Celsius or 200 degrees Fahrenheit. These remarkable highly specialized molecules are the key to understanding how cells function.

Please choose a topic from one below:

  1. The Nature of Proteins:Composition
  2. Catalysts
  3. Lock and Key Model For Enzyme Activity
  4. Induced Fit Model For Enzyme Activity
  5. Temperature Effects On Enzyme Activity
  6. pH Effects On Enzyme Activity
  7. Competitive and Non-Competitive Inhibitors of Enzyme Activity

    The Nature of Proteins

    Enzymes are indeed protein in nature consisting of alpha amino acid monomeric building blocks. These amino acid molecules are connected by the removal of two Hydrogens and an Oxygen atom from an amino group (-NH2) and a carboxyl group (COOH) of two amino acid molecules. This is referred to as a condensation reaction.(See Fig 1 below)

    Peptide Formation

    As this linkage occurs, the protein molecule begins to take shape. These linkages are referred to as peptide bonds, and small polymeric molecules are referred to as "poly peptides". However, once enough of these amino acid molecules have condensed to form a chain large enough to influence its own shape (usually 30 amino acids), then the polymer becomes known as a protein. Proteins serve a number of biochemical functions such as anatomical structural features of organisms and as nutrient carriers, antigens, and hormones.

    Proteins are often associated with a non-protein compound usually by conjugation. These groups are referred to as prosthetic groups. The protein part of this association is called the apoenzyme. Other enzymes are associated with a heavy metal or ions called a metallo-protein. Other enzymes require the loose association with a metal which helps the enzyme to position the substrate molecule into the active site. These are called activators. Examples are Copper, Cobalt, Zinc, Magnesium, Molybdimum, and Manganese. Molecules loosely associated with the enzyme are called co-enzymes. Examples are vitamins like riboflavin, B vitamins, Vitamin C, and others serve as co-enzymes.

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    Catalysts

    Proteins serve as biochemical catalysts in perhaps their greatest and most important role. Catalysts are substances that increase product formation by (1) lowering the energy barrier (activation energy) for the product to form

    and (2) increases the favorable orientation of colliding reactant molecules for product formation to be successful.

    There are two types of catalysts:

    1. Heterogeneous Catalysts
    2. Homogeneous Catalysts

    Heterogeneous catalysts are those that provide a surface for the reaction to proceed upon. The catalyst and the reactant molecules are not in the same phase. This is sometimes referred to as surface catalysts. Certain transition state metals like Pladium, Platinum, Nickel, and Iron serve as industrial catalysts that catalyze a wide variety of reactions such as Hydrogenation.

    Homogeneous catalysts are catalysts that exist in the same phase as the reactant molecules usually in a solution. Acids and Bases in solution serve as catalysts in a wide variety of Organic reactions. Most industrial catalysts are responsible for more than one catalysis among reactants and are considered relatively non-specific in what they catalyze. Enzymes are very different. All current research suggests that enzymes are extremely specific in what a given enzyme catalyzes. Indeed, most enzyme molecules catalyze only one specific reaction but it does so in a phenomenally efficient manner. One enzyme molecule might be responsible for converting thousands of reactant molecules called substrate molecules into product.

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    Lock and Key Model For Enzyme Activity

    The high specificity and efficiency of enzymes can be explained by the manner that they associate with the reactant molecules called the substrate. One of the first theories or models that help to explain this phenomenally efficient catalytic efficiency of enzymes is called the "lock and key" model. According to this model, each enzyme molecule may have as few as one active site on the surface of the enzyme molecule itself. An active site is an indentation or cavity whereby a reactant molecule (substrate) is attracted to. This is called the enzyme-substrate complex. The polar and non-polar groups of the active site attract compatible groups on the substrate molecule so that the substrate molecule can effectively lock into the cavity and position itself for the necessary collisions and bond breaks and formations that must take place for successful conversion to a product molecule. Once the product molecule has been formed the electrical attractions that made the substrate molecule adhere to the active site no longer are present, and the product molecule can disengage itself from the active site thus freeing the site for another incoming substrate molecule. This process occurs in a highly efficient manner hundreds or even thousands of times in a short time span. This model assumes that molecules that lock into the active site must form a perfect fit. Also the assumption is that the active site conformation is ridged. Evidence does not support these assumptions. For example, certain "bogus" molecules can lock into the active site even though the bogus molecules have a different shape compared to the true substrate molecule. This has the effect of inhibiting enzyme activity. This does not seem to support the ridged active site assumption in the lock and key model. Furthermore, small temperature changes and small changes in pH will not result in the enzyme being inhibited from catalyzing its intended reaction. The occurance of pH and temperature ranges of optimum enzyme activity does not support the assumptions made by the lock and key model of ridged active site cavities. Modification of the lock and key model is necessary to account for the occurance of pH and temperature ranges of optimum enzyme activity and to explain why other molecules can effectively block the active site.

    Induced Fit (Hand and Glove) Model of Enzyme Activity

    Modification of the lock and key model assumes that the active site has a certain amount of elasticity whereby the active site can expand or contract in a limited way in order to accomodate the substrate molecule. The analogy is like a hand fitting into a glove. The glove adjusts in shape and size to fit various sized hands within a certain range. This tolerance would explain why bogus molecules of slightly different size compared to the true substrate molecule can still be accomodated by the elastic active site. Small changes in temperature would distort the active site conformation but not so much that the active site could not still accomodate the substrate molecular size. PH changes which would also change the active site conformation but not so much that the active site could not flexibly accomodate the substrate molecule. The Induced Fit Model seems to explain why there is some flexibility in the abilility of the active site to accomodate other molecules and at limited temperature and pH ranges.

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    Factors Of Enzyme Inhibition

    A number of things can happen to throw a monkey wrench into this remarkably efficient process.

    Temperature Effects on Enzyme Activity

    Every enzyme has a temperature range of optimum activity. Outside that temperature range the enzyme is rendered inactive and is said to be totally inhibited. This occurs because as the temperature changes this supplies enough energy to break some of the intramolecular attractions between polar groups (Hydrogen bonding, dipole-dipole attractions) as well as the Hydrophobic forces between non-polar groups within the protein structure. When these forces are disturbed and changed, this causes a change in the secondary and tertiary levels of protein structure, and the active site is altered in its conformation beyond its ability to accomodate the substrate molecules it was intended to catalyze. Most enzymes (and there are hundreds within the human organism) within the human cells will shut down at a body temperature below a certain value which varies according to each individual. This can happen if body temperature gets too low (hypothermia) or too high (hyperthermia).

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    pH Effects on Enzyme Activity

    Changes in the pH or acidity of the environment can take place that would alter or totally inhibit the enzyme from catalyzing a reaction. This change in the pH will affect the polar and non-polar intramolecular attractive and repulsive forces and alter the shape of the enzyme and the active site as well to the point where the substrate molecule could no longer fit, and the chemical change would be inhibited from taking place as efficiently or not at all. In an acid solution any basic groups such as the Nitrogen groups in the protein would be protonated. If the environment was too basic the acid groups would be deprotonated. This would alter the electrical attractions between polar groups. Every enzyme has an optimum pH range outside of which the enzyme is inhibited. Some enzymes like many of the hydrolytic enzymes in the stomach such as Pepsin and Chymotrypsin effective operate at a very low acidic pH. Other enzymes like alpha amylase found in the saliva of the mouth operate most effectively at near neutrality. Still other enzymes like the lipases will function most effectively at basic pH values. If the pH drops in the blood called acidosis then enzymes in the blood will be inhibited outside their optimal pH range. If the pH climbs to an unacceptably high value called alkalosis then enzymes cease to function effectively. Normally, these conditions do not take place because of the highly efficient buffers found in the blood that restrict the pH of the blood to a very narrow range. Buffers are a substance or mixtures of substances that resist any change in the pH. There are many buffer systems found in the body to adjust the pH so that enzymes might continue to catalyze their reactions.

    Correcting pH or temperature imbalances will usually allow the enzyme to resume its original shape or conformation. Some substances when added to the system will irreversably break bonds disrupting the primary structure so that the enzyme is inhibited permanently. The enzyme is said to be irreversably denatured. Many toxic substances will break co-valent bonds and cause the unraveling of the protein enzyme. Other toxic substances will precipitate enzymes effectively removing them from the solution thus preventing them from catalyzing the reaction. This is also called denaturation.

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    Competitive and Non-Competitive Inhibition of Enzymes

    Competitive Inhibition occurs when a bogus molecule that is close enough to the shape of the true substrate will fit into the active site. Once locked into position, the blocker molecule prevents the true substrate molecule from getting into position. This effectively blocks the active site. The bogus molecule competes for the active site with the true substrate molecule. Many toxic substances owe their toxic properties to their ability to act as inhibitors to important enzymes responsible for catalyzing important biochemical processes. Once the enzyme is inhibited the process cannot take place, and a toxicological symptom occurs that often leads to paralysis, coma or even death of the organism. For example, cyanide poisoning is due to the cyanide ion competitively inhibiting the active site of the cytochromases enzymes responsible for catalyzing the Oxidation and Reduction processes of the Electron Transport System which is responsible for cellular respiration.

    Other inhibitors latch themselves not to the active site itself but to some portion of the enzyme molecule close to the active site which results in the changing of the shape of the active site. This is referred to as non-competitive inhibition. Many heavy metals like Lead, Mercury,and Chromium will function as non-competitive inhibitors. Toxicology is the study of how toxicological substances can interfere with life sustaining enzymes via inhibition.

    The pesticide and herbicide industries make use of competitive and Non-Competitive Inhibitors

    Biological warfare owes its success to enzyme inhibition but so does the life giving chemotherapeutic treatment of cancerous tumor growths with agents that inhibit important cancel cell enzymes. All in all the use of inhibitors can be used for the benefit of mankind or its destruction.

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    Nomenclature of Enzymes

    Enzymes have a functional name which classifies the enzyme in terms of what kind of reaction the enzyme catalyzes. The following classification names apply:

    1. Oxidoreductases- These are enzymes that catalyze oxidations or reductions. Enzymes such as dehyrogenases, oxidases, and peroxidases.
    2. Transferases- These enzymes catalyze the transfer of a group from one molecule to another. Examples such as Phosphatases, transaminases, and transmethylases.
    3. Hydrolases-These enzymes catalyze hydrolysis reactions. Examples are the digestive enzymes such as sucrase, amylase, maltase, and lactase.
    4. Lyases- These enzymes catalyze the removal of groups in non-aqueous media. An example would be the decarboxylases.
    5. Isomerases- Enzymes that catalyze the isomerization of molecules. Examples are racemases, and cis-trans isomerases.
    6. Ligases- These are also called synthetases which are enzymes that catalyze condensation reactions where smaller molecules are connected with the resulting removal of a water molecule. This is accompanied with the formation of a high energy Phosphate link that stores energy. An example would be the amino acid RNA ligases.

    In addition to the classification name most enzymes have group names.

    1. Hydrolases-Enzymes that catalyze hydrolysis reactions.
    2. hydrogenases- Enzymes that catalyze the addition of Hydrogen atoms
    3. Oxidases- Enzymes that catalyze oxidations

    In addition each enzyme has a specific name which usually consists of part of the name of the substrate molecule. Examples are sucrase, Maltase, Lactase, galactosidase, and RNAase. Other enzymes have retained common names attributed to them. Such enzymes as Pepsin, Chymotrypsin, Trypsin, Catalase, Alpha Amylase, Lysozyme, and others.

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    R. H. Logan, Instructor of Chemistry, Dallas County Community College District, North Lake College.



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    All textual content copyrighted (c) 1996
    R.H. Logan, Instructor of Chemistry, DCCCD
    All Rights reserved
    

    Revised: 10/28/97

    URL:http://edie.cprost.sfu.ca/~rhlogan/enzymes.html