ENZYMES &CLINICAL ENZYMOLOGY Prepared by: Assistant professor Dr.Sumreena Mansoor Vignette 5 • Presenting complaint: A 50 year old man complains of severe retrosternal pain radiating to his left arm and jaw. • Medical History: Severe chest pain on exertion that is relieved by sitting down. He is hypertensive and is on ACE inhibitors for the last two years • Examination: Anguished, dyspneic male, with hand clutched to chest. He is nauseated and has vomited a few times. • Family History: His father died of a Myocardial Infarction and his younger brother is also taking ACE inhibitors. • Investigations: EKG, CK-MB, LDH, Troponin I & T • Emergency treatment: Injection streptokinase • Diagnosis: Myocardial Infarction (MI) ENZYME DIAGNOSTICS ISOENZYMES Catalyze the same reaction. Differ in AA sequence and physical properties Separable on the basis of charge. Are tissue specific. Isoenzymes Different Isoenzymes may arise from different tissues and their specific detection may give clues to the site of pathology. ENZYMES NAME OF THE ENZYME PRESENT IN Aspartate Amino transferase (AST) Serum glutamate-oxaloacetate transaminase (SGOT) Heart and Liver Alanine Amino transferase (ALT) Serum glutamate-pyruvate transaminase (SGPT) Heart and Liver Alkaline Phosphatase (ALP) Bone, intestine and other tissues Acid Phosphatase (ACP) Prostate glutamyl Transferase ( GT) Liver Creatine kinase (CK) Muscle Including cardiac muscle Lactate Dehydrogenase (LDH) Heart, liver, muscle, RBC Amylase Pancreas LACTATE DEHYDROGENASE (LDH) Pyruvate Lactate (anaerobic glycolysis) LDH is elevated in myocardial infarction, blood disorders It is a tetrameric protein and made of two types of subunits namely H = Heart, M = skeletal muscle It exists as 5 different isoenzymes with various combinations of H and M subunits Isoenzyme Composition Composition name Present in Elevated in LDH1 ( H 4) HHHH Myocardium, RBC myocardial infarction LDH2 (H3M1) HHHM Myocardium, RBC LDH3 (H2M2) HHMM Kidney, Skeletal muscle LDH4 (H1M3) HMMM Kidney, Skeletal muscle LDH5 (M4) MMMM Skeletal muscle, Liver Skeletal muscle and liver diseases LACTATE DEHYDROGENASE IN MI CREATINE KINASE (CK) Creatine kinase is a dimer made of 2 monomers occurs in the tissues Skeletal muscle contains M subunit, Brain contains B subunits Three different isoenzymes are formed Isoenzyme name Composition Present in Elevated in CK-1 BB Brain CNS diseases CK-2 MB Myocardium/ Heart Acute myocardial infarction MM Skeletal muscle, Myocardium CK-3 ALANINE TRANSAMINASE (ALT) AND ASPARTATE TRANSAMINASE( AST) - Oxoglutarate + L-aspartate Aspartate aminotransferase (AST) L- glutamate + oxaloacetate - Oxoglutarate + L-alanine Alanine aminotransferase (ALT) L - glutamate + pyruvate Alanine transaminase (ALT) and Aspartate transaminase (AST) enzymes are the most abundantly present in the liver and is elevated in blood as a result of leakage from damaged cells Alanine transaminase (ALT) increase is specific for liver damage involving hepatocellular damage Aspartate transaminase (AST) is moderately increased in Muscular dystrophy and acute myocardial infarction LEVELS OF ENZYMES IN DISEASES INVOLVING LIVER DAMAGE In viral hepatitis Rapid rise in transaminases (AST & ALT) in serum occurs even before bilirubin rise is seen LEVELS OF ENZYMES IN MYOCARDIAL INFARCTION AST and CK rise in 6 hours following acute myocardial infarction LDH are elevated much later and remains high for a longer period of days LDH CK CK-MB AST SUMMARY Enzymes are biological catalysts present in every cell of the body. An enzyme will act on a specific substrate yielding a product. An isoenzyme is a genetic variant produced largely within a specific tissue. Isoenzyme patterns can give information about organ-specific disease. Important enzymes in the investigation of heart disease are CK, LDH and AST. Important enzymes in the investigation of liver disease are AST, ALT. Creatine kinase has three isoenzymes: CK-MM, CK-MB and CK-BB. LDH has five isoenzymes. Alkaline phosphatase can be used in the investigation of liver and bone disease. Increased levels of acid phosphatase are found in prostate cancer.