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:

Harper’s Illustrated Biochemistry

Biochemistry – Satyanarayana

Medline Plus : Isoenzyme tests