Q5
LONG ANSWER
10M
★ High-yield
Describe the diagnostic importance of serum enzymes. Give the enzyme profile in myocardial infarction and liver disease. Add a note on isoenzymes.
Principle
Diagnostic enzymology = measurement of enzyme activity in plasma to detect and monitor tissue damage.Enzymes appear in plasma when cells are damaged, when their turnover increases, or when their excretion is obstructed.
| Group | Meaning | Example |
|---|---|---|
| Plasma-specific (functional) | Act in plasma; synthesised by the liver | Clotting factors, lipoprotein lipase, pseudocholinesterase |
| Non-plasma-specific | Have no function in plasma; leak from tissue | All the diagnostic enzymes |
| Secretory | Normally secreted into a duct | Amylase, lipase, alkaline phosphatase |
Cardiac Markers
| Marker | Rises | Peaks | Returns to normal | Comment |
|---|---|---|---|---|
| Myoglobin | 1–3 h | 6–9 h | 24 h | Earliest but non-specific |
| CK-MB | 4–6 h | 24 h | 48–72 h | Best for detecting RE-infarction, as it normalises quickly |
| Troponin I and T | 4–6 h | 24–48 h | 7–10 days | Most sensitive and specific; the gold standard |
| Ast | 12 h | 24–48 h | 3–5 days | Non-specific |
| LDH | 12–24 h | 48–72 h | 8–14 days | Useful in late presentation |
- Troponin has replaced all others for diagnosis; the others retain value only for timing
Liver Enzymes
| Enzyme | Chief significance |
|---|---|
| ALT (SGPT) | More specific for liver; markedly raised in viral hepatitis (> 10×) |
| Ast (SGOT) | Liver, heart, muscle. ast:ALT > 2 suggests alcoholic liver disease |
| Alkaline phosphatase | Markedly raised in obstructive jaundice and bone disease (Paget, rickets, metastases) |
| GGT | Most sensitive index of alcohol intake; rises with ALP in cholestasis, confirming a hepatic rather than bony source |
| 5′-nucleotidase | Confirms that a raised ALP is of hepatobiliary origin |
Other Diagnostic Enzymes
| Enzyme | Raised in |
|---|---|
| Amylase and lipase | Acute pancreatitis; lipase is more specific and stays up longer |
| Creatine kinase (CK-MM) | Duchenne muscular dystrophy (very high), rhabdomyolysis, myositis |
| Acid phosphatase | Carcinoma prostate (now superseded by PSA) |
| Pseudocholinesterase | Decreased in liver disease and organophosphate poisoning |
| Aldolase | Muscle disease |
| ACE | Sarcoidosis |
Isoenzymes and Their Diagnostic Value
Isoenzymes = physically distinct forms of an enzyme catalysing the same reaction, but differing in structure, kinetics and electrophoretic mobility.
Lactate dehydrogenase — 5 isoenzymes
- A tetramer of H (heart) and M (muscle) subunits
- LDH-1 (H4) — heart and RBC
- LDH-2 (H3M) — reticuloendothelial system; normally the highest in serum
- LDH-3 — lung; LDH-4 — kidney, placenta
- LDH-5 (M4) — liver and skeletal muscle
- "Flipped pattern" LDH-1 > LDH-2 indicates myocardial infarction
Creatine kinase — 3 isoenzymes
- CK-MM — skeletal muscle; CK-MB — heart; CK-BB — brain
Factors to Consider Before Interpreting a Raised Enzyme
- Tissue specificity — how confined is the enzyme to one organ?
- Timing — when did the injury occur relative to the sample?
- Magnitude — a rise of 10× means something different from 1.5×
- Half-life — determines how long the abnormality persists
- Route of clearance — renal or hepatic failure may raise levels without tissue damage
- Physiological causes — ALP rises in growing children, in pregnancy, and after a fatty meal (intestinal isoenzyme)
- Artefacts — haemolysis of the sample falsely raises LDH, ast and potassium
Applied Aspects
- Enzymes are used therapeutically too — streptokinase and urokinase as thrombolytics, asparaginase in leukaemia, pancreatin in pancreatic insufficiency
- Enzymes as laboratory reagents — glucose oxidase for blood glucose, urease for urea, and horseradish peroxidase in ELISA
- Timing matters — a normal troponin within 4 hours of chest pain does not exclude infarction; the test must be repeated
- The pattern of enzymes is more informative than any single value — ALT with ALP, or ast with ALT, localises the disease far better than either alone
- Serial measurement beats a single reading — a falling trend indicates recovery, a rising one continuing damage
- Normal enzymes do not exclude disease — in established cirrhosis the transaminases may be normal because little viable liver remains
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.