SN2
SHORT NOTE
5M
★ High-yield
Define isoenzymes. Describe the isoenzymes of lactate dehydrogenase and creatine kinase with their clinical significance.
Definition
Isoenzymes (isozymes) = multiple molecular forms of the same enzyme that catalyse the same reaction but differ in amino acid sequence, physical and kinetic properties, and tissue distribution.
- They arise from different genes, different alleles, or different combinations of subunits
- Separated by electrophoresis, differing in charge and mobility
Lactate Dehydrogenase
- A tetramer of two kinds of subunit — H (heart) and M (muscle) → 5 isoenzymes
| Isoenzyme | Subunits | Chief source | Note |
|---|---|---|---|
| LDH-1 | H4 | Heart, RBC, kidney | Rises in myocardial infarction and haemolysis |
| LDH-2 | H3M | Reticuloendothelial system | Normally the highest in serum |
| LDH-3 | H2M2 | Lung | Pulmonary embolism |
| LDH-4 | HM3 | Kidney, placenta | — |
| LDH-5 | M4 | Liver, skeletal muscle | Rises in hepatitis and muscle injury |
CLINICAL PEARL
Flipped pattern — when LDH-1 exceeds LDH-2, suspect myocardial infarction (or haemolysis, or megaloblastic anaemia). Normally LDH-2 is the highest.
Creatine Kinase
| Isoenzyme | Subunits | Source | Clinical use |
|---|---|---|---|
| CK-1 (BB) | BB | Brain | Rarely used |
| CK-2 (MB) | MB | Cardiac muscle | Myocardial infarction; best marker of RE-infarction |
| CK-3 (MM) | MM | Skeletal muscle | Muscular dystrophy, rhabdomyolysis |
Other Important Isoenzymes
- Alkaline phosphatase — liver, bone, intestinal and placental forms; the bone form rises in Paget disease and rickets, the placental form in pregnancy
- Hexokinase and glucokinase — the classic example of isoenzymes with different Km, allowing liver and brain to handle glucose differently
- Amylase — salivary (S) and pancreatic (P) types, distinguishing mumps from pancreatitis
Applied Aspects
- Isoenzyme analysis localises the damaged tissue when the total enzyme is raised but its source is uncertain — the chief diagnostic value
- Macro-enzymes — enzyme bound to immunoglobulin; gives a persistently raised value with no disease, and can cause needless investigation
- Troponin has largely replaced CK-MB and LDH isoenzymes in cardiac diagnosis, but the principle remains examinable and is still used in other tissues
All questions in Enzymes
- Q1Define enzymes. Classify them according to the IUBMB system and describe the mechanism of enzyme action. Add a note on enzyme specificity. ★
- Q2Describe the effect of substrate concentration on enzyme activity. Explain the Michaelis–Menten equation, the significance of Km and the Lineweaver–Burk plot. ★
- Q3Classify enzyme inhibition. Describe competitive, non-competitive and uncompetitive inhibition with their effects on Km and Vmax, and give examples. ★
- Q4Describe the mechanisms regulating enzyme activity. Explain allosteric regulation, covalent modification and enzyme induction with examples. ★
- Q5Describe the diagnostic importance of serum enzymes. Give the enzyme profile in myocardial infarction and liver disease. Add a note on isoenzymes. ★
- SN1Define coenzymes. Enumerate the coenzymes derived from vitamins with their functions. ★
- SN2Define isoenzymes. Describe the isoenzymes of lactate dehydrogenase and creatine kinase with their clinical significance. ★
- SN3Describe allosteric enzymes with their characteristics and examples. Add a note on feedback inhibition. ★
- SN4Define zymogens. Give examples and explain their physiological importance. ★
- SN5Define Km. Describe its significance with the example of hexokinase and glucokinase. ★
- SN6Describe competitive inhibition with its characteristics and medically important examples. ★
- SN7Describe the types of enzyme specificity with examples.