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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.

Biochemistry · 1st Professional — Pre-Clinical

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.

GroupMeaningExample
Plasma-specific (functional)Act in plasma; synthesised by the liverClotting factors, lipoprotein lipase, pseudocholinesterase
Non-plasma-specificHave no function in plasma; leak from tissueAll the diagnostic enzymes
SecretoryNormally secreted into a ductAmylase, lipase, alkaline phosphatase

Cardiac Markers

MarkerRisesPeaksReturns to normalComment
Myoglobin1–3 h6–9 h24 hEarliest but non-specific
CK-MB4–6 h24 h48–72 hBest for detecting RE-infarction, as it normalises quickly
Troponin I and T4–6 h24–48 h7–10 daysMost sensitive and specific; the gold standard
Ast12 h24–48 h3–5 daysNon-specific
LDH12–24 h48–72 h8–14 daysUseful in late presentation
  • Troponin has replaced all others for diagnosis; the others retain value only for timing

Liver Enzymes

EnzymeChief 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 phosphataseMarkedly raised in obstructive jaundice and bone disease (Paget, rickets, metastases)
GGTMost sensitive index of alcohol intake; rises with ALP in cholestasis, confirming a hepatic rather than bony source
5′-nucleotidaseConfirms that a raised ALP is of hepatobiliary origin

Other Diagnostic Enzymes

EnzymeRaised in
Amylase and lipaseAcute pancreatitis; lipase is more specific and stays up longer
Creatine kinase (CK-MM)Duchenne muscular dystrophy (very high), rhabdomyolysis, myositis
Acid phosphataseCarcinoma prostate (now superseded by PSA)
PseudocholinesteraseDecreased in liver disease and organophosphate poisoning
AldolaseMuscle disease
ACESarcoidosis

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

  1. Q1Define enzymes. Classify them according to the IUBMB system and describe the mechanism of enzyme action. Add a note on enzyme specificity. ★
  2. Q2Describe the effect of substrate concentration on enzyme activity. Explain the Michaelis–Menten equation, the significance of Km and the Lineweaver–Burk plot. ★
  3. Q3Classify enzyme inhibition. Describe competitive, non-competitive and uncompetitive inhibition with their effects on Km and Vmax, and give examples. ★
  4. Q4Describe the mechanisms regulating enzyme activity. Explain allosteric regulation, covalent modification and enzyme induction with examples. ★
  5. Q5Describe the diagnostic importance of serum enzymes. Give the enzyme profile in myocardial infarction and liver disease. Add a note on isoenzymes. ★
  6. SN1Define coenzymes. Enumerate the coenzymes derived from vitamins with their functions. ★
  7. SN2Define isoenzymes. Describe the isoenzymes of lactate dehydrogenase and creatine kinase with their clinical significance. ★
  8. SN3Describe allosteric enzymes with their characteristics and examples. Add a note on feedback inhibition. ★
  9. SN4Define zymogens. Give examples and explain their physiological importance. ★
  10. SN5Define Km. Describe its significance with the example of hexokinase and glucokinase. ★
  11. SN6Describe competitive inhibition with its characteristics and medically important examples. ★
  12. SN7Describe the types of enzyme specificity with examples.

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