Enzymes in Clinical Diagnosis

Study Notes

Functional enzymes are secreted into the blood by certain cell types.
- Example: Liver secretes zymogens (inactive precursors) involved in blood coagulation.
Non-functional enzymes are released from cells during normal turnover and have no physiologic use in the plasma.
- Levels are fairly constant in healthy individuals, reflecting a balance between release and removal.
- Increased plasma levels of non-functional enzymes may indicate tissue damage.

Abundant in the liver.
Elevated plasma levels suggest possible damage to hepatic tissue
- Normal levels:
  - Male: 13-35 U/L
  - Female: 10-30 U/L
ALT levels may rise several days before clinical signs, such as jaundice.
Moderate increase (25-100 U/L) can be seen in chronic liver diseases like cirrhosis and liver malignancy.
Very high values (100-1000 U/L) are observed in acute hepatitis, both toxic and viral.

Isoenzymes (isozymes) catalyze the same reactions in different organs.
They have different physical properties due to variations in amino acid sequence.
Their patterns in plasma can help identify the site of tissue damage.

CK exists as three isoenzymes:
- CK1 = BB
- CK2 = MB
- CK3 = MM
Each isoenzyme is a dimer composed of two polypeptides (B and M subunits).
They exhibit distinct electrophoretic mobility.
- Virtually all CK in the brain is BB.
- Skeletal muscle primarily contains MM.
- Cardiac muscle contains about one-third MB and the rest MM.

CK2 (MB) isoenzyme is used for diagnosing MI because it is the only tissue containing more than 5% of total CK activity as CK2 (MB).
Following an acute MI, CK2 (MB) appears in the blood approximately 4-8 hours after chest pain onset.
Peaks in activity around 24 hours.
Returns to baseline after 48-72 hours.

Regulatory proteins involved in myocardial infarction.
Released into plasma in response to cardiac damage.
Cardiac Troponin I (cTnI):
- Highly sensitive and specific for cardiac tissue damage.
- Appears in plasma within 4-6 hours after an MI.
- Peaks in 8-28 hours.
- Remains elevated for 3-10 days..
Elevated serum troponins are more predictive of adverse outcomes in unstable angina or myocardial infarction than CK2.

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