(clinical biochemistry of enzymes) Clinical enzymology (clinical biochemistry of enzymes)

Introduction Enzymes are found in small amounts mainly within cells ,clotting factors and digestive enzymes function naturally after secretion: - Plasma specific – Thrombin - Secreted - Lipase, Amylase - Intracellular - transaminases, creatine kinase Injury or death of tissues can cause the release of tissue-specific enzymes into the bloodstream. Elevated enzyme levels are often indicators of tissue problems, and are used in the diagnosis of diseases. Enzyme activities in the body fluids are altered by pathological processes so, its measurement is used for disease investigation

What are the clinically important enzymes? Liver enzyme: Alanine aminotransferase (ALT; old name SGPT) is normally found largely in the liver Liver, heart, muscle, kidney, and brain: Aspartate aminotransferase (AST; old name SGOT) is normally found in a diversity of tissues Bone enzyme: Alkaline phosphatase (ALP) Brain, heart, muscle: Creatine kinase (CK; old name CPK) Lactate dehydrogenase (LD; old name LDH)

Isozymes Multiple forms of same enzyme Catalyse same reaction Differ in molecular weight ,structure and charge Have different Km for same substrate Important in diagnosis of diseases

Creatine kinase Creatine kinase is associated with ATP regeneration in muscle and nervous tissue. Elevated blood levels of CK are used as indicators of MI, muscular dystrophy, and stroke. CK occurs as a dimer of 2 different subunits, M and B.         - CK-1-BB: Brain type.         - CK-2-MB: Hybrid type (cardiac & skeletal muscle).         - CK-3-MM: Muscle type. These can be separated by electrophoresis. CK-MB is released from cardiac muscle cells after MI.

Lactate dehydrogenase (LDH or LD) Converts pyruvate to lactate (and vice versa) during and after anaerobic metabolism. LDH occurs as a tetramer of 2 different subunits: LD-1 (HHHH) from the heart: Elevated after MI.      LD-2 (HHHM) from the kidney: Elevated after renal infarction.      LD-3 (HHMM) from the lung, spleen and pancreas: Elevated in pulmonary embolism. LD-4 (HMMM) and LD-5 (MMMM), both from the liver and skeletal muscle: Elevated in injury to liver or skeletal muscle.

Serum Enzymes in Disease Myocardial infarction

Myocardial infarction Necrosis of the myocardium, but not angina pectoris release of CK, AST and LDH (HBD) into the circulation. CK is the first to rise (activity within 6 h of MI ). Total CK reaches a peak at 24-36 h. In uncomplicated cases, CK returns to normal within 3 days. Serum AST  more slowly ( maximum activity within 48 h) and returns to normal in 4-5 days. No significant elevation in HBD seen for the 1st 24 h (reaches maximum at about 3 days & remain  for up to 8 days). It is important to consider the timing of sample when interpreting test results. CK & HBD are useful as early and late indicators of MI, and more specific than AST.

Myocardial infarction CK from skeletal muscle may be  following intramuscular injection, chest compression for resuscitation or electrical defibrillator. CK specificity is  by measuring CK-MB. HBD activity may be  due to non cardiac factors (hemolysis). Cardiac enzyme measurements are very sensitive indicators of MI because it is  in over 95% of cases. They are of particular value in the following conditions: Atypical clinical presentation (absence of chest pain) If the patient presents some time after a suspected event. Difficulty in interpreting ECG (Arrhythmia or previous MI). If further MI is suspected few days of a previous one.