ENZYMES &CLINICAL ENZYMOLOGY

2. ENZYMES &CLINICAL ENZYMOLOGY Prepared by: Assistant professor Dr.Sumreena Mansoor

3. 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)

4. ENZYME DIAGNOSTICS

5. ISOENZYMES • Catalyze the same reaction. • Differ in AA sequence and physical • properties • Separable on the basis of charge. • Are tissue specific.

6. Isoenzymes • Different Isoenzymes may arise from different tissues and their specific detection may give clues to the site of pathology.

7. ENZYMES

8. 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

10. LACTATE DEHYDROGENASE IN MI

11. 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

14. ALANINE TRANSAMINASE (ALT) AND ASPARTATE TRANSAMINASE( AST) - Oxoglutarate + L-alanine - Oxoglutarate + L-aspartate Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) L- glutamate + oxaloacetate 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

15. 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

17. 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 AST CK CK-MB

20. 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.

21. THANK YOU!