Lec 9 Role of Enzymes in Diagnosis of Diseases PDF

Lippincott’s illustrated reviews Chapter 5, Page 64 Lectures 9 Role of Enzymes in Clinical Diagnosis of Diseases 1  Specific Objectives By the end of this lecture students can be able to: Differentiate between functional and nonfunctio...

Lippincott’s illustrated reviews Chapter 5, Page 64 Lectures 9 Role of Enzymes in Clinical Diagnosis of Diseases 1  Specific Objectives By the end of this lecture students can be able to: Differentiate between functional and nonfunctional enzymes. Discuss ALT as indicator for liver diseases. Define the Isoenzyme. Know the role of CK isoenzyme and troponine in the diagnosis of MI.  Enzymes in Clinical Diagnosis Plasma enzymes can be classified into two major groups. First, (functional enzyme), a relatively small group of enzymes are actively secreted into the blood by certain cell types. For example, the liver secretes zymogens (inactive precursors) of the enzymes involved in blood coagulation. Second, (non-functional enzyme), a large number of enzyme species are released from cells during normal cell turnover. These enzymes almost always function intracellularly, and have no physiologic use in the plasma.  In healthy individuals, the levels of these enzymes are fairly constant, and represent a steady state in which the rate of release from damaged cells into the plasma is balanced by an equal rate of removal of the enzyme protein from the plasma.  Increased plasma levels of these enzyme may indicate tissue damage. Determining the degree of elevation of a particular enzyme activity in the plasma is often useful in evaluating the prognosis for the patient.  Plasma enzymes as diagnostic tools The enzyme alanine aminotransferase (ALT) is abundant in the liver. The appearance of elevated levels of ALT in plasma signals possible damage to hepatic tissue.  Normal serum level of ALT for male is 13-35 U/L and for female is 10-30 U/L. Rise in ALT levels may be noticed several days before clinical such as jaundice is manifested. Moderate increase (25 to 100 U/L) may be seen in chronic liver diseases such as cirrhosis, and malignancy in liver. Very high values (100 to 1000 U/L) are seen in acute hepatitis, either toxic or viral in origin.  Isoenzymes and diseases of the heart Most isoenzymes (also called isozymes) are enzymes that catalyze the same reaction in different organs. They do not have the same physical properties because of genetically determined differences in amino acid sequence. The pattern of isoenzymes found in the plasma may, therefore, serve as a means of identifying the site of tissue damage.  For example, the plasma levels of creatine kinase (CK) are commonly determined in the diagnosis of myocardial infarction. They are particularly useful when the electrocardiogram is difficult to interpret, such as when there have been previous episodes of heart disease.  Creatine kinase isoenzymes Creatine kinase (CK) occurs as three isoenzymes. Each isoenzyme is a dimer composed of two polypeptides (called B and M subunits) associated in one of three combinations: CK1 = BB, CK2 = MB, and CK3 = MM. Mucks Brand muded Each CK isoenzyme shows a characteristic electrophoretic mobility. Note: Virtually all CK in the brain is the BB isoform, whereas in skeletal muscle it is MM. In cardiac muscle, about one-third is MB with the rest as MM  Diagnosis of myocardial infarction Measurement of blood levels of CK2 (MB) isoenzyme is used in diagnosis of myocardial infarction (MI) because myocardial muscle is the only tissue that contains more than 5% of the total CK activity as the CK2 (MB) isoenzyme.  Following an acute MI, this isoenzyme appears in approximately 4-8 hours following onset of chest pain, reaches a peak of activity at approximately at 24 hours, and return to baseline after 48-72 hours.  Troponin I or Troponin T are regulatory proteins involved in myocardial infarction. They are released into plasma in response to cardiac damage. Cardiac troponin I (cTnI) is highly sensitive and specific for damage of cardiac tissue. cTnI appears in plasma within 4-6 hours after an MI, peaks in 8-28 hours, and remains elevated for 3-10 days.  Elevated serum troponins then, are more predictive of adverse outcomes in unstable angina or myocardial infarction than the conventional assay of CK2. No Reference Book: Champe, P. C., Harvey, R. A. and Ferrier, D. R., 2005. Biochemistry “Lippincott’s Illustrated Reviews”, 5th or 6th Edition 22