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ENZYMES. ENZYMES Elino, M.M.H. OVERVIEW of ENZYMES. Enzymes – are biologic catalysts.
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ENZYMES Elino, M.M.H. OVERVIEW of ENZYMES Enzymes – are biologic catalysts. Catalysts are substances that increase the speed of a chemical reaction, it is not permanently changed, nor does it cause the reaction to occur, that is, a catalyst can increase the speed of a reaction but cannot cause that reaction if it would not occur in the absence of catalyst. Since catalysts are not used up, they can be used over and over again.
ENZYMES Elino, M.M.H. OVERVIEW of ENZYMES Enzymes – are organic catalyst produced by an organisms. The reactant in an enzyme-catalyzed reaction is called “substrate”.
ENZYMES Elino, M.M.H. OVERVIEW of ENZYMES The small portion of the molecule that is responsible for the catalytic action of the enzyme is the “active site”.
ENZYMES Elino, M.M.H. OVERVIEW of ENZYMES Enzymes are superior to other catalysts in several ways: 1. They have a much greater catalytic power. CO2 + H2O carbonic anhydrase H2CO3
ENZYMES Elino, M.M.H. OVERVIEW of ENZYMES 2. Enzymes are highly specific with varying degrees of specifity. Absolute specifity – they act on one substrate and only on that substrate. Stereospecifity – such enzymes that can detect the difference between optical isomers (mirror images) and select only one of such isomers. Reaction specifity – enzymes that catalyze certain types of reactions.
ENZYMES Elino, M.M.H. OVERVIEW of ENZYMES Group specifity – enzymes that catalyzes a group of substances that contain specific compounds. 3. The activity of enzymes is closely regulated, whereas the catalyst is difficult to control.
ENZYMES Elino, M.M.H. ENZYME REACTION Enzymes are proteins and therefore undergo all the reactions that proteins do. That is, enzymes can be coagulated by heat, alcohol, strong acids, and alkaloidal reagents. Temperature Requirement The higher the temperature, the faster the rate of reaction. The best temperature for enzyme function – the temperature at which the rate of a reaction involving an enzyme is the greatest – is called the “optimum temperature”.
ENZYMES Elino, M.M.H. ENZYME REACTION Role of pH Each enzyme has a pH range within which it can best function. This is called “optimum pH range” for that particular enzyme. For example, the optimum pH range of pepsin, an enzyme found in gastric juice, is approximately 2.0, whereas the optimum pH range of trypsin, an enzyme found in pancreatic juice, is near 8.2.
ENZYMES Elino, M.M.H. ENZYME REACTION If the pH of a substrate is too far from the optimum pH required by the enzyme, that enzyme cannot function at all. However, since body fluids contains buffers, the pH usually does not vary too far from the optimum values.
ENZYMES Elino, M.M.H. ENZYME REACTION Effect of Concentration As with the all chemical reactions, the speed is increased with an increase in concentration of reacctants. With an increased concentration of substrate, the rate of the reaction will increase until available enzyme becomes saturated with substrate. Also with an increase in the amount of enzyme, the rate of reaction will increase, assuming an unlimited supply of substrate.
ENZYMES Elino, M.M.H. ACTIVATORS and INHIBITORS Activators – inorganic substances that tend to increase the activity of enzyme. Inhibitors – any substance that will make the enzyme less active or render it inactive. Competitive inhibitors – binds reversibly in the active site and so block the access by the substrate. Incompetitive inhibitors – bind to another site on the enzyme to render it less active or inactive.
ENZYMES Elino, M.M.H. ACTIVATORS and INHIBITORS Irreversible inhibitors – form strong covalent bonds with the enzymes, rendering it inactive. This effect can’t be overcome by increasing the concentration of the substrate.
ENZYMES Elino, M.M.H. ACTIVATORS and INHIBITORS Poisons Many enzymes inhibitors are poisonous because their effect on enzyme activity. Mercury and Lead compounds are poisonous because they react with sulfhydryl groups ( - SH) of an enzymes and so change its conformation. The subsequent loss of enzyme activity leads to the various symptoms of lead and mercury poisoning, such as loss of equilibrium, hearing, sight, and touch, which are generally irreversible.
ENZYMES Elino, M.M.H. ACTIVATORS and INHIBITORS Drugs While some enzyme inhibitors are poisonous, others are beneficial to life. Pencillin acts as an enzyme inhibitor for transpeptide, a substance that bacteria need to build their cell walls. If the cell wall is lacking, osmotic pressure causes the bacterial cell to burst and die. However, new strains of bacteria have developed an enzyme, penicillinase, that inactivates penicillin. To destroy these new strains, synthetically modified penicillins have been prepared so that this antibiotic remains effective.
ENZYMES Elino, M.M.H. MODE OF ENZYME ACTIVITY
ENZYMES Elino, M.M.H. MODE OF ENZYME ACTIVITY
ENZYMES Elino, M.M.H. ACTIVATORS and INHIBITORS Lock-and key Model Wherein the substrate must “fit” into the active site of the enzyme – hence the specifity of the enzyme. Induced-Fit Model Suggests that the active site is not rigid as the Lock-and-Key Model, but flexible. That is, the site changes in conformation upon binding to a substrate in order to yield an enzyme-substrate fit.
ENZYMES Elino, M.M.H. APOENZYMES and COENZYMES Other enzymes are conjugated proteins – they contain a protein and non-protein part. Both parts must be present before the enzyme can function. The protein part is called the “apoenzyme” and the non-protein (organic part) is called “coenzyme”.
ENZYMES Elino, M.M.H. APOENZYMES and COENZYMES Coenzymes are not proteins and so are not inactivated by heat. Examples of coenzymes are the vitamins or compounds derived from vitamins. The reaction involving a coenzyme can be written as follows: coenzyme + apoenzyme = enzyme Coenzyme A is essential in the metabolism of carbohydrates, lipids, and proteins in the body.
ENZYMES Elino, M.M.H. NOMENCLATURE Formerly enzyme were given names ending in “-in”. With no relation being an indicator between the enzyme and the substance it affects – the substrate. The current system for naming enzymes uses the name of the substrate or the type of reaction involved, with the ending “-ase”.
ENZYMES Elino, M.M.H. NOMENCLATURE
ENZYMES Elino, M.M.H. CLASSIFICATION Oxidoreductases – are enzymes that catalyze oxidation-reduction reactions between two substrates. The enzymes of the oxidation- reduction reactions in the body are important because these reactions are responsible for the production of heat and energy. Transferases – are enzymes that catalyze the transfer of a functional group between two substrates.
ENZYMES Elino, M.M.H. CLASSIFICATION Hydrolases – hydrolytic enzymes – catalyze the hydrolysis of carbohydrates, esters and proteins. Lyases – are enzymes that catalyzes the removal of groups from substrates by means other than hydrolysis, usually with the formation of double bonds.
ENZYMES Elino, M.M.H. CLASSIFICATION Isomerases –are enzymes that catalyze the interconversion of cis-trans isomers. Ligases – or synthetases, are enzymes that catalyze the coupling of two compounds with breaking of pyrophosphate bonds.
ENZYMES Elino, M.M.H. ENZYMES of the KIDNEY If an individual’s blood pressure drops, as in the case of hemorrhaging or in hypokalemia, the kidneys secrete the enzyme renin (sometimes considered as a hormone) into the bloodstream. angiotensinogen renin angiotensin I converting enzyme angiotensin II Angiotensin II increases the force of the heartbeat and constricts the arterioles, thus causing an increase in blood pressure.
ENZYMES Elino, M.M.H. ENZYMES of the KIDNEY Angiotensin II brings about the contraction of smooth muscle and also triggers the release of the hormone aldosterone which aids in the retention of water. Actually, angiotensin I is the most powerful vasoconstrictor known. It is an octapeptide; Angiotensin I is a decapeptide.
ENZYMES Elino, M.M.H. ENZYMES of the KIDNEY Other kidney enzymes include glucose-6-phosphatase, which is involved in the removal of the phosphate group from glucose-6-phosphate, thereby enabling glucose to diffuse from the cell into the blood stream; Glutaminase, which is involved in the conversion of glutamine into glutamic acid and NH4+ ; and a hydroxylase, which is involved in the synthesis of calcitriol.
ENZYMES Elino, M.M.H. CHEMOTHERAPY Chemotherapy is the use of chemicals to destroy infectious microorganisms and cancerous cells without damaging the host’s cells. These chemicals function by inhibiting certain cellular enzyme reactions. Among the chemotherapeutic agents are the antibiotics and the antimetabolites.
ENZYMES Elino, M.M.H. CHEMOTHERAPY Antibiotics – are compounds produced by one microorganisms that are toxic to another microorganisms. Among the most commonly used are the penicillin and tetracyclin.
ENZYMES Elino, M.M.H. CHEMOTHERAPY Penicillin Tetracycline
ENZYMES Elino, M.M.H. CHEMOTHERAPY Antimetabolites – are chemicals that have structures closely related to those of the substrate enzymes act on, thus inhibiting enzyme activity. Mercaptopurine are used in the treatment of leukemias. Some are antibiotics.
ENZYMES Elino, M.M.H. CHEMOTHERAPY One of the most promising new chemotherapeutic agent in decades is taxol, a natural product obtained from the bark of Pacific yew trees. Taxol acts by interfering with cellular growth and function and is very effective in shrinking a variety of tumors, particularly in advanced cases of ovarian and breast cancer.
ENZYMES Elino, M.M.H. CLINICAL SIGNIFICANCE OF PLASMA ENZYME CONCENTRATIONS The measurement of plasma enzyme levels can be of great diagnostic value. Many other plasma enzymes are useful in the diagnosis of various diseases.
ENZYMES Elino, M.M.H. CLINICAL SIGNIFICANCE OF PLASMA ENZYME CONCENTRATIONS
ENZYMES Elino, M.M.H. CLINICAL SIGNIFICANCE OF PLASMA ENZYME CONCENTRATIONS
ENZYMES Elino, M.M.H. ISOZYMES Isozymes or Isoenzymes are enzymes with the same function but slightly different structural features. The reason for their existence is not unknown, but they are made use of clinically. Lactate dehydrogenase (LDH), creatinekinase, and alkaline phosphatase all occur in isoenzyme form and are diagnostic value. LDH has five forms.
ENZYMES Elino, M.M.H. CLINICAL SIGNIFICANCE OF RELATIVE AMOUNT OF LDH
ENZYMES Elino, M.M.H. ALLOSTERIC REGULATION Allosteric regulation is the regulation of an enzyme or other protein by binding an effector molecule at the enzyme's allosteric site (that is, a site other than the active site). Effectors that enhance the protein's activity are referred to as allosteric enzymes, whereas those that decrease the protein's activity are called noncompetitive inhibitors.
ENZYMES Elino, M.M.H. ALLOSTERIC REGULATION Allosteric regulation This control of key enzymes is utmost importance to ensure that biologic processes remain coordinated at all times to meet the immediate metabolic needs of the cells.
ENZYMES Elino, M.M.H. ZYMOGENS Zymogens are inactive pprecursors of enzymes. Most digestive and blood-clotting enzymes exist in the zymogen form, until activated. In the case of digestive enzymes, this is necessary to prevent digestion of pancreatic and gastric tissue. For blood clotting, it is to avoid premature of blood cells.
ENZYMES Elino, M.M.H. ZYMOGENS
ENZYMES Elino, M.M.H. ZYMOGENS Lactose Intolerance Individuals who cannot eat food containing lactose are said to be lactose intolerant. They lack enzyme lactase, which is requires for the hydrolysis of lactose. As a result, lactose acuumulates in the intestinal tract and pulls water out of the tissues by osmosis. This is turn causes abdominal cramps, distention, and diarrhea.
ENZYMES Elino, M.M.H. ZYMOGENS Lactose Intolerance To overcome such an effect today, an individual may take Lactaid orally to supply the missing enzyme.
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