Enzymes in Medicine PDF

ENZYMES IN MEDICINE  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: sever...

ENZYMES IN MEDICINE  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 (enzymotherapy). Diagnostic tools: used in clinical laboratory assays.  ENZYMES IN CLINICAL DIAGNOSIS Secretory: Produced by tissues (namely liver), acting in plasma: prothrombin, plasminogen, cerruloplasmin, choline esterase; lipoprotein lipase Enzymes Intracellular: have no physiological use in plasma  membrane bound – ALP  cytosolic – ALT, AST  mitochondrial – Glyoxysomal malate dehydrogenase (gMDH)  lysosomal - Acid phosphatase (ACP) is a hydrolytic lysosomal enzyme secreted by a number of cells including prostate, bones and other tissues.  tissue specific – glucose-6-phosphatase – liver amylase – pancrease LD1 – heart  Healthy individuals: levels of intracellular enzymes fairly constant and low –the rate of enzyme release from damaged cells into plasma balanced by the rate of removal of enzyme from plasma.  Physiological enzyme levels  reference values of the enzyme activities (determined in clinical laboratory) 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.  ALTERATION OF ENZYME PLASMA LEVELS Increased values – increased cell membrane permeability -disturbances of energy metabolism  cytosolic enzymes – ALT, LD, CK - cell necrosis  membrane-bound enzymes – ALP mitochondrial enzymes –GMDH - induction of the enzyme synthesis  drugs – ALP Decreased values – inhibition of the activity  drugs - inhibition of the synthesis  cell damage, drugs  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 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  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  ENZYMOTHERAPY Orally administered enzymes : Mixtures of plant and/or animal origin enzymes for treatment of a variety disorders for examples digestive, gastrointestinal, and pancreatic disorders.  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 - inflammatory diseases, edema - immune and autoimmune diseases (arthritis, multiple sclerosis) - viral diseases (herpes, AIDS) - cancer  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  NUCLEOTIDE STRUCTURE Nucleotides nitrogenous base + pentose + phosphate group(s) purine ribose 1-3 pyrimidine deoxyribose other (nicotinamide) Nucleosides  ATP - adenosine triphosphate adenine phosphate chain NH2 O O O N N - O P O P O P O O- O- O- CH2 N N O OH OH ribose AMP ADP ATP cAMP – cyclic adenosine monophosphate cAMP  NH2 | C N N C CH HC C N N CH2 O - O H H H H O P O OH O- cAMP – cyclic adenosine monophosphate -intracellular mediator, second messenger of hormonal signal tranduction via adenylate cyclase cascade - mechanism of action: allosteric effector  NUCLEOTIDE FUNCTION Precursors of DNA, RNA Energy transport – ATP, ADP, AMP Allosteric effectors of enzymes: allosteric effector is a molecule that binds to the site of an allosteric enzyme, causing a change in configuration resulting in an increase (positive effector) or reduction (negative effector) in enzyme activity Intracellular mediators (= second messengers) – cAMP, cGMP Coenzymes – NAD+, NADP+, FAD