Clinical Enzymology - A Comprehensive Overview PDF

Clinical enzymology Enzymes - Remarkable molecules found in living organisms that play a crucial role in various biological processes - Helps us to break down food, convert nutrients into energy, build and repair tissues - Multitasking superheroes that enable life's chemical reacti...

Clinical enzymology Enzymes - Remarkable molecules found in living organisms that play a crucial role in various biological processes - Helps us to break down food, convert nutrients into energy, build and repair tissues - Multitasking superheroes that enable life's chemical reactions to happen efficiently What are enzymes? - Found in all living cells - Made of protein - Biological catalysts - Speed up reactions - Unchanged by the reaction Enzyme nomenclature - According to the name of substrate with the addition of the suffix "ase" -- protease, lipase - According to the type of reaction they catalyze -- kinase, dehydrogenase - According to the numerical designation given by the Enzyme Commission CLASSIFICATION OF ENZYMES **OXIDOREDUCTASE** - OXIDATION REDUCTION REACTION Removal or addition of electrons 2 general types OXIDASES Specific example: CYTOCHROME OXIDASE DEHYDROGENASES Specific examples: LDH (LACTATE DEHYDROGENASE) ML (MALATE DEHYDROGENASE) ICD (ISOCITRATE DEHYDROGENASE) G-6-PD (GLUCOSE-6-PHOSPHO DEHYDROGENASE) **TRANSFERASES** - Transfer the chemical group from one subscript to another Specific examples: AST (ASPARTATE TRANSAMINASE) ALT (ALANINE TRANSAMINASE) CK/CPK (CREATINE KINASE / CREATININE PHOSPHOKINASE) GGT (GAMMA GLUTAMYL TRANSAMINASE) OCT (ORNITHINE CARBONYL TRANSFERASE) **HYDROLASES** - Split of a bond by the admission of water Specific examples: **ESTERASES** ACP (ACID PHOSPHATSE) LPS (LIPASE) CNS (CHOLINESTERASE) **PEPTIDASES** PTS (TRYPSIN) PPS (PEPSIN) **GLUCOSIDASES** AMS (AMYLASE) AMYLO-1-6-GLUCOSIDASE GALACTOSIDASES **LYASES** - Remove the groups from the substrate without hydrolysis, leaving only double bonds in the molecules **ISOMERASES** - Catalyzed the intramolecular rearrangement of the substrate compound Specific example: = GLUCOSE PHOSPHATE ISOMERASE TERMS ASSOCIATED WITH ENZYMES HALOENZYMES -- active substance form by the accommodation of apo enzymes and halo enzymes APO ENZYMES -- protein portion subject to dematuration **CO-FACTOR** \- non protein substance Examples: **CO-ENZYMEMS** - Organic molecules - Dialyzable portion of the halo enzymes Examples: NAD (NICOTINAMIDE ADENINE DINUCLEOTIDE) NADP (NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE) VITAMINS **ACTIVATOR** **ISOENZYMES** **METALLOENZYMES** **PROENZYMES** - Also called as ZYMOGENS Substrate - Subs acted upon by enzymes which are specific for each of their particular enzymes Enzyme assay A. PHOSPHATASES - Ability to hydrolyze a large variety of organic phosphate ALP DISEASES POSSIBLE DISEASES = OSTEITIS DEFORMANS = HYPERPARATHYROIDISM = BONE NEOPLASM ISOENZYME = LIVER = BONE = INTESTINE = PLACENTA CLINICAL SIGNIFICANCE - INCREASED HEPATOBILIARY DIDEASE = Intrahepatic Obstruction = Tuberculosis Granulomas = Tumor Metastasis - BONE DISEASES W/ OSTEOBLASTIC ACTIVITY = Osteoblastic Tumor = Rickets = Osteomalacia - MODERATE ELEVATION - DECREASE IN HYPOPHOSPHATASIA AND MALNUTRIRION = Hodkin disease = CHF = Regional Enteritis = Ulcerative colitis ACP INHIBITORS - L-tartrate ion - Formaldehyde and Cupric ions CLINICAL SIGNIFICANCE - HIGHEST ELEVATION ARE SEEN IN METASTASIZING CARCINOMA OF THE PROSTRATE - MODERATE ELEVATION OF THE TOTAL ACP = FEMALE BREAST CA = PAGET'S DISEASE - NON-PROSTATIC ACP ELEVATION = NIEMAN PICK DISEASE = GAUCHER'S DISEASE = MYELOCTIC LEUKEMIA - PRESENCE IN SEMINAL FLUID B. AMYLASE / DIASTASE / ALPH-1; 4-GLUCAN; 4-GLUCANOHYDROLASE / AMS - Split complex CHO like starch and glycogen via hydrolysis to form maltose and maltodextrin ISOENZYMES - SALIVARY AMYLASE / PTYALIN - PANCREATIC AMYLASE / AMYLOPSIN CLINICAL SIGNIFICANCE: - ACUTE PANCREATITIS - ELEVATED LEVELS = MUMPS = PERFORATED PEPTIC ULCER = APPENDICITIS = RAPTURED ECTOPIC PREGNANCY = BILIARY TRACT DISEASE C. LIPASE / TRIACYL GLYCEROL ACELHYDROLASE / LPS - It catalyze the hydrolysis of esters in the alpha position of triglycerol to yield beta monoglycerides and FA ISOENZYMES - PANCREATIC - ARTERIAL - GASTRIC - SUBLINGUAL LIPASE CLINICAL SIGNIFICANCE - In acute pancreatitis, LPS becomes more elevated within the 1^st^ 12 hours and remain for several days - Also elevated in pancreatic duct obstruction, and tumor of the pancreas PRINCIPLE OF LIPASE - Major source of LIPASE if the PANCREAS - Lipase breaks down the triglycerides into smaller components which can be absorbed across the small intestine. D. AMINOTRANSFERASES ISOENZYMES - ASPARTATE AMINOTRANSFERASES / GLUTAMATE OXALOACETATE TRANSAMINASE / AST / SGOT = an enzyme belonging to the class of transferases. It is commonly referred to as transaminase and is involved in the transfer of an amino group between aspartate and alpha-keto acids - ALANINE AMINOTRANSFERASE / GLUTAMATE PYRUVATE TRANSAMINASE / ALT / SGPT = a transferase with enzymatic activity similar to that of AST. Specifically, it catalyzes the transfer of an amino group from alanine to alpha-ketoglutarate with the formation of glutamate and pyruvate AST CLINICAL SIGNIFICANCE - MI -- one of the early enzymes that rise in serum level of AST - INCREASED LEVEL ALSO SEEN IN THE FOLLOWING = Pulmonary Infraction = Pericarditis = Acute Hepatitis = Skeletal Muscles - USED TO dx OF CHRONIC ABUSE AND HEPATOXICITY - DECREASED IN PREGNANT WOMAN ALT CLINICAL SIGNIFICANCE - ACUTE OR CHRONIC VIRAL HEPATITIS - MI - HEPATOCELLULAR DISEASE E. LACTATE DEHYDROGENASE / LDH - An enzyme that catalyzes the interconversion of lactic and pyruvic acid. It is hydrogen transfer enzymes that use the co-enzyme NAD TISSUE SOURCE - LD is widely distributed in the body. Very high activities are found in the heart, liver, skeletal muscle, kidney, and erythrocytes. It is present in lesser amounts in the lungs, mouth, muscle and brain. ISOENZYMES : LDH1 (HHHH) : LDH2 (HHHM) : LDH3 (HHMM) : LDH4 (HMMM) : LDH5 (MMMM) OPTIMUM Ph CLINICAL SIGNIFICANCE - MYOCARDIAL INFARCTION - ALSO INCREASE IN THE FOLLOWING : LIVER DISEASE : MUSCLE TRAUMA : HEMOLYTIC DISEASE : PERNICIOUS ANEMIA - MODERATELY TO MARKEDLY ELEVATED : MEGALOBLASTIC ANEMIA : PULMONARY INFRACION : GRANULOCYTIC LEUKEMIA : HEMOLYTIC ANEMIA : INFECTIOUS MONONUCLEOSIS (IM) F. CREATINE KINASE / APT-CREATINE-N-PHOSPHOTRANSFERASE / CK - Promotes the intercoversion of creatine and ATP to creatine phosphate and ADP, finishing biochemical energy for muscle contraction TISSUE SOURCE - Widely distributed in tissues, with highest activities found in skeletal muscle, heart muscle and brain. Other sources in smaller quantities include the bladder, placenta, gastrointestinal tract, thyroid, uterus, kidney, lungs, prostate, spleen, liver and pancreas. ISOENZYMES - CK1 or BB - CK2 or MB - CK3 or MM OPTIMUM pH - Forward rxn: 9.0 - Backward rxn: 6.8 CLINICAL SIGNIFICANCE - MYOCARDIAL INFARCTION - INCREASED LEVEL = PROGRESSIVE MUSCULAR DYSTROPHY = POLYMYOSITIS = ACUTE PSYCHOSIS = ALCHOHOLIC MYOPATHY = DELIRIUM TREMENS = HYPOTHYROIDISM = MALIGNANT HYPERTHERMIA =TRICHINOSOS = DERMATOMYCOSIS = ACUTE CEREBROVASCULAR DISEASE NV - Male: 15-160 U/L at 37'C - Female: 15-130 U/L at 37'C G. FRUCTOSE DIPHOSPHATE ALDOLASE / ALD - Catalyze the splitting of D-fructose diphosphate to D-glyceraldehyde phosphate and dihydroxy acetone phosphate ISOENZYMES - ALDOLASE A - ALDOLASE B - ALDOLASE C ENZYMES CLINICAL SIGNIFICANCE --------- ------------------------------------ ACP PROSTATIC CARCINOMA ALT HEPATIC DISRDERS ALP HEPATIC AND BONE DISORDERS AMS ACUTE PANCREATITIS AST HEPATIC, SKELETAL/MUSCLE DISORDERS CK MYOCARDINAL INFARCTION (MI) LDH MI, CARCINOMAS, HEPATIC DISORDERS LPS ACUTE PANCREATITIS SUMMARY MYOCARDIAL INFARCTION - CK -- MB followed by CK -- MM - AST - LDH HEPATIC DISEASE - AST - ALT - LDH - ALP MUSCLE DISORDERS - AST - CK - ALD ACUTE PANCREATITIS - INCREASE IN AMYLASE AND LIPASE -