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Description : Check out this medical presentation on Alanine Aminotransferase (alanine transaminase), which is titled "Enzymes in medicine", to know about the use of enzymes in medicine.

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Published on : Jul 05, 2021 | Views : 1554 | Downloads : 4

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ENZYMES IN MEDICINE
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Diagnostic indicators – the activities of many enzymes are routinely determined in plasma ( rarely in tissue biopsies) for diagnostic purposes in diseases of the heart, liver, skeletal muscle, pancreas and other tissues - enzyme diagnostics Therapeutic agents – several enzymes are used as drugs; new approach - enzymotherapy Diagnostic tools – use as chemicals in clinical laboratory assays
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ENZYMES IN CLINICAL DIAGNOSIS secretory - produced by tissues (namely liver), acting in plasma – prothrombin, plasminogen, cerruloplasmin, choline esterase; lipoprotein lipase Enzymes intracellular – function intracellulary, have no physiological use in plasma - membrane bound – ALP, GMT - cytosolic – ALT, AST, LD, MDH - mitochondrial – AST, GMDH - lysosomal - ACP - tissue specific – glucose-6-phosphatase – liver amylase – pancrease LD1 – heart
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Healthy individuals - levels of intracellular enzymes fairly constant, low – the rate of enzyme release from damaged cells into plasma balanced by the rate of removal of enzyme protein from plasma  Physiological enzyme levels  reference values of the enzyme activities (determined in clinical laboratory – each lab has its own reference values) Elevated enzyme activity in the plasma – reflect tissue damage accompanied by increased release of intracellular enzyme Skeletal muscle during exertion – physiologically elevated levels of muscle enzymes in plasma Many diagnostically important enzymes = isoenzymes – pattern of isoenzymes in plasma (determined electroforetically) – a means of identifying the damaged tissue
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ALTERATION OF ENZYME PLASMA LEVELS Increased values – increased cell membrane permeability anoxia, disturbances of energy metabolism  cytosolic enzymes – ALT, LD, CK - cell necrosis  membrane-bound enzymes – ALP, GMT mitochondrial enzymes – AST, GMDH - induction of the enzyme synthesis  drugs – ALP, GMT Decreased values – inhibition of the activity  drugs - inhibition of the synthesis  cell damage, drugs
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Examples of enzymes commonly assayed for diagnostic purposes Enzyme Location Cause of elevated plasma level Acid phosphatase - ACP Prostate Prostatic cancer Alkaline phosphatase – ALP Bone, liver Rickets, hypoparathyroidism, osteomalacia, obstructive jaundice, cancer of bone/liver Alanine aminotransferase – ALT Liver (muscle, Hepatitis, jaundice, circulatory heart, kidney) faillure with liver congestion Aspartate aminotransferase – AST Heart, muscle, Myocardial infarction, muscle red cells, liver damage, anemia, hepatitis, circulatory faillure with liver congestion Amylase - AM Pancres Acute pancreatitis, peptic ulcer -Glutamyl transferase – GMT Liver, kidney, Hepatitis, alcoholic liver pancreas damage, cholestasis
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Examples of isoenzymes commonly assayed for diagnostic purposes Enzyme Location Cause of elevated plasma level Creatine kinase – CK CK-MB Heart Myocardial infarction CK-MM Skeletal muscle Muscular dystrophy Lactate dehydrogenase – LD LD1 > LD2 Heart, kidney, Myocardial infarction, kidney blood cells disease, megaloblastic anemia, leukemia LD2, LD3 Leukemia LD5 Liver, muscle Liver disease, muscle damage
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ENZYMES IN THERAPY Substitution of missing production of digestive enzymes – digestive enzymes – pepsin trypsin… Removal of deposits of death tissue or fibrin (e.g. in lungs, eyes), treatment of skin defects – proteinases, nucleases, collagenase Acceleration of fibrinolysis in lungs embolization (activation of plasmin and plasminogen) – streptokinase, urokinase
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ENZYMOTHERAPY Orally administered enzymes – treatment of a variety disorders - digestive, gastrointestinal, pancreatic - inflammatory diseases, edema - immune and autoimmune diseases (arthritis, multiple sclerosis) - viral diseases (herpes, AIDS) - cancer Mixtures of enzymes of plant and/or animal origin - proteinases, amylase, lipase - administered as acidoresistent tablets Pancreatin – trypsin, chymotrypsin, lipase, amylase Wobenzym – pancreatic and plant proteolytic enzymes – trypsin, chymotrypsin, papain (Carica papaya), bromelain (ananas) = combination of enzymes with different specificity, pH optimum, stability, interaction with inhibitors and antiproteinases  multiple action
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Mechanism of resorption (transport of large macromolecules across the intestinal barrier) – paracellular transport, receptor mediated endocytosis and transcytosis Mechanism of action – interaction with plasma antiproteinases – 1-antitrypsin, 2-macroglobulin complexes direct proteolytic action, degradation of adhesive molecules, secretion of cytokins (tranforming growth factor TGF-), modulation of receptor function not fully clarified ?
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ENZYMES - USE IN LABORATORY ASSAYS Enzymes isolated from different sources - used for determination of various substances in the blood, plasma/serum and urine  enzyme methods much more specific than chemical methods, the presence of relative substances with similar chemical properties does not hinder Components of commercial kits or diagnostic strips - determination of glucose - glucose oxidase, peroxidase cholesterol - cholesterol esterase, cholesterol oxidase peroxidase, urea – urease, ……. in blood, plasma, serum - proof of glucose (glucose oxidase), …….. in blood or urine (strips) Markes in the immunochemical analysis - ELISA (=enzyme-linked immunoadsorbent assay) – peroxidase, alkaline phosphatase
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NUCLEOTIDES Structure, Function
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NUCLEOTIDE STRUCTURE Nucleotides nitrogenous base + pentose + phosphate group(s) purine ribose 1 - 3 pyrimidine deoxyribose other (nicotinamide) Nucleosides
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adenine guanine cytosine thymine uracil THE NITROGENOUS BASES Purine bases Pyrimidine bases
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NUCLEOSIDE A sugar - base combination. Base Sugar In this case deoxyribose -N-glycosidic linkage N
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HOCH2 OH HOCH2 HOCH2 O O H OH thymine uracil cytosine deoxythymidine uridine cytidine
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HOCH2 HOCH2 HOCH2 OH OH adenine guanine hypoxanthine deoxyadenosine guanosine inosine !
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NUCLEOTIDES 5’-OH on the sugar of a nucleoside is converted into a phosphate ester. deoxyadenosine monophosphate (dAMP) Each is named based on sugar and base name and then the number of phosphates is indicated.
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ATP - adenosine triphosphate ATP ADP AMP
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NUCLEOTIDE FUNCTION Precursors of DNA, RNA - NTPs Energy transport - ATP Allosteric effectors of enzymes – ATP, ADP, AMP Covalent modification of enzymes – ATP Intracellular mediators (= second messengers) – cAMP, cGMP Coenzymes – NAD+, NADP+, FAD, CoA-SH Activated precursors of polysaccharaides, glycoproteins, proteoglycans, phospholipids, glycolipids – UDPG, UDPGA, UDPGal…, CDP-choline, CDP-diacylglycerol… Active groups (group transport) – SAM, PAPS
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NAD+ reactive site nicotinamide adenine ribose
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FAD
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Coenzyme A
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H OH O H OH H OH H OH CH 2 OH H
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Non-polar tail O C O O C O C C CH2 H H H P O O O - -O-
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cAMP cAMP – cyclic adenosine monophosphate
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P O O O O- O CH2 cAMP – cyclic adenosine monophosphate intracellular mediator, second messenger of hormonal signal tranduction via adenylate cyclase cascade - mechanism of action: allosteric effector
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