Lecture 7 Enzymes in clinical practice

By Dr Nivan Zoheiry

Overview


Reactions in human body is mediated by enzymes, which are Globular protein catalysts that increase the rate of the reactions without being changed in the overall process

Clinical Uses of Enzymes



Enzymes are used clinically in three principal ways: 1-In diagnosis and prognosis of various disease 2-As analytical reagents in the measurement of activity of other enzyme or non-enzyme substances 3-As therapeutic agents

Isoezymes


Isoezymes: are different formes of given enzyme having the same catalytic activity, but differ in some physical or chemical properties. Thus each isoenzyme will act on the same substrate and give the same product. LDH, ALP and CPK are enzymes having isoenzymes.

Enzymes as Therapeutic Agents



Some enzymes are used in treatment of certain

diseases. 1-Digestive enzymes, 2-Anti-inflammatory agents that reduce swelling and help clear away debris. Papain also has analgesic and anti-inflammatory action. 3-Pancreatic enzymes do have a powerful anticancer effect on pancreatic cancer and multiple myleoma.

4- Streptokinase is a enzyme produced by beta-haemolytic streprococus and is used as an effective clot-dissolving medication in some cases of myocardial infarction and pulmonary embolism Defective enzyme can result from genetic mutation, or infection by bacteria or viruses ,The development of Enzyme replacement therapy (ERT) has brought hope to individuals with some rare, inherited diseases.

ERT


ERT is not a cure for any condition; but it treats the deficient enzyme activity. ERT is safe and effective; however, it is costly

Diagnosis and Prognosis



Destruction of cells. Tissue damage or necrosis resulting from injury or disease is accompanied by increase in levels of enzymes. By measuring the level of certain enzymes in plasma it helpes in the diagnosis and prognosis of many diseases Isozymes of lactate dehydrogenase (LDH) are used in MI diagnosis Creatinine kinase (CK) used MI and Muscle disorders

Enzymes which may indicate alterations in liver health.



Alanine Aminotransferase: ALT Cell damage will cause elevations of A-LT due to leakage. The elevation of the enzyme correlates with the number of cells damaged. Falling levels of ALT may indicate recovery or may indicate a failing number of functional liver cells. Rapid increases in ALT may indicate an acute process, while slow increases may indicate bile duct obstruction.

Aspartate Aminotransferase: AST enzyme seen in the liver, heart, kidney, skeletal muscle and brain, AST elevations and ALT elevations should parallel each other in liver disease Alkaline Phosphatase ALP This enzyme is present in many tissues, therefore it is not very specific in liver disease, but it appears very early in the progress of liver disease, therefore it is considered quite sensitive

Site-directed mutagenesis


Site-directed mutagenesis has been widely used in the study of protein functions. There are many approaches were a mutation being added to DNA strand in a certain site Site-directed mutagenesis (modification of amino acid sequence of known enzymes) is used for design new drug therapy

Ribozymes and catalytic antibodies



Abzymes - Abzymes are antibodies that catalyze specific chemical reactions, i.e. function as enzymes. Antibodies by definition have evolved to recognise and bind to the ground states of the molecules they are specific to. In contrast, enzymes have binding sites that preferentially bind to the transition state of their substrate molecules For this reason abzymes are not produced naturally

Ribozymes


Ribozymes are RNA molecules with catalytic activity. And concerned with RNA metabolism as splicing In higher eukaryotic cells, show that RNA can act as an enzyme. This has revolutionized thinking about enzyme action and the origin of life itself.