Isoenzymes and their Diagnostic Importance

Isoenzymes:

  • Also called isozymes
  • Are multiple forms of an enzyme that catalyzes the same reaction
  • Arise through gene duplication
  • Differ in their physical and chemical properties, Km and Vmax values, optimum pH, substrate affinity, etc.

Lactate Dehydrogenase (LDH)

Lactate ←LDH→ Pyruvate

LDH is a tetrameric enzyme with 2 types of subunit “H” and “M” :

  1. M (for muscle) : basic
  2. H (for heart) : acidic

Isoenzymes of LDH:

  1. LDH1 (H4) : Heart and RBC
  2. LDH2 (H3M) : Heart and RBC
  3. LDH3 (H2M2) : Brain and kidney
  4. LDH4 (HM3) : Liver and skeletal muscle
  5. LDH5 (M4) : Liver and skeletal muscle

LDH1 has high Km (low affinity) and LDH5 has low Km (high affinity) for pyruvate.

Diagnositc importance of LDH:

  1. Normal: LDH2 > LDH1
  2. Myocardial infarction (within 12-24 hours): LDH1>>LDH2 (flipped LDH pattern)
  3. Liver diseases: increased LDH5 in serum
  4. Increased LDH suggests other following diseases:
    • Hemolytic anemia
    • Hypotension
    • Infectious mononucleosis
    • Intestinal ischemia and infarction
    • Muscle injury
    • Muscular dystrophy
    • Pancreatitis
    • Lung tissue death
    • Stroke
    • Ischemic cardiomyopathy

Creatine Phosphokinase (CPK)

Phosphocreatine ←CPK→ Creatine

CPK is a dimeric enzyme consisting of 2 subunits:
a. M : for muscle
b. B : for brain

Isoenzymes of CPK:

  1. CPK1 (BB) : Brain
  2. CPK2 (MB) : Heart
  3. CPK3 (MM) : Skeletal muscles

Diagnositic importance of CPK:

  1. Normal: low CPK2 (<2%) in serum
  2. MI (within 6-18 hrs): increased CPK2 (20%) in serum
  3. Increased CPK-1 suggests:
    • Brain cancer
    • Brain injury
    • Pulmonary infarction
    • Seizure
  4. Increased CPK-2 suggests other diseases like:
    • Electrical injuries
    • Heart injury
    • Myocarditis
  5. Increased CPK-3 suggests:
    • Crush injuries
    • Rhabdomyolysis
    • Muscular dystrophy
    • Myositis
    • Recent seizures

Alkaline Phosphatase (ALP):

The enzyme is a monomer and the isoenzymes are due to the difference in the carbohydrate content:

  1. Alpha1-ALP
  2. Alpha2-Heat labile ALP
  3. Alpha2-Heat stable ALP
  4. Pre Beta-ALP
  5. Gamma-ALP ,etc.

Diagnostic importance of ALP:

  1. Increased Alpha2-Healt labile ALP:
    • Liver diseases : Biliary obstruction, hepatitis
  2. Increased pre beta-ALP:
    • Bone diseases: Paget’s disease, Osteoblastic bone tumors, Osteomalacia, Rickets, Skeletal disease
  3. Increase in ALP also suggests other diseases like:
    • Pregnancy
    • Healing bone fracture
    • Anemia
    • Leukemia
    • Thyroid gland inflammation
    • Hyperparathyroidism
    • Chronic alcohol ingestion
  4. Decreased ALP suggests:
    • Malnutrition

Sources:

One Response
  1. November 11, 2016

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