Enzymes
- Definition : Specialized proteins that act as biological catalyst
- Exception : Ribozymes (RNA)
- GRPS
Ribozyme | Location | Function |
Group II introns | - | RNA splicing |
Ribonuclease P | Nucleus | Post-transcriptional modification of tRNA |
Peptidyl transferase | 28S rRNA | Translation |
snRNA | Spliceosome | RNA splicing |
Isoenzymes
- Same reaction, Different kinetics, different morphology
Properties
- Products of different genes
- Same reaction, different genes.
- Example: Salivary amylase, Pancreatic amylase.
- Subunits may be different
- Formed by different combinations of subunits.
- Examples: LDH (1–5), CK (1–3).
- Different electrophoretic mobility
- Structural differences (charge) → migrate differently.
- LDH 1 → fastest,
- LDH 5 → slowest.
- CK 1 → fastest,
- CK 3 → slowest.
- Differ in heat stability
- Heat-stable vs. heat-labile isoenzymes.
- Example: Isoenzymes of ALP.
- Differ in substrate specificity
- Same general reaction but affinity differs.
- Example:
- Glucokinase (only glucose),
- Hexokinase (all hexoses).
- Differ in cofactor requirement
- Need different cofactors or forms.
- Example:
- Isocitrate dehydrogenase
- Cytoplasmic (NADP+),
- Mitochondrial (NAD+).
Isoenzymes as Diagnostic Markers
- Indicate location of injury
- Liver: ALT
- Heart: AST, CK-MB
- Bone: ALP
- Indicate severity of injury
- Reversible injury: Cytoplasmic enzymes ↑ (membrane permeability).
- Irreversible injury: Mitochondrial enzymes ↑ (mitochondrial damage).
- Markers of Hepatic Injury:
- S. ALT
- S. AST
- Markers of Cholestasis:
- S. ALP
- 5' nucleotidase
- S. GGT
Creatine Kinase (CK):
Isoenzyme | Subunits | Electrophoretogram | Tissue Localization | % in Serum | Clinical Significance |
CK-1 | BB | Fastest | Brain | 1% | CVA |
CK-2 | MB | Intermediate | Heart | 5% | MI |
CK-3 | MM | Slowest | Skeletal Muscle | 80% | Muscle injury, Myopathies |
Lactate Dehydrogenase (LDH) Isoenzymes
- Convert Pyruvate → Lactate
Isoenzyme | Subunits | Electrophoretogram | Tissue Localization | % in Serum |
LDH-1 | H₄ | Fastest | Heart | 30% |
LDH-2 | H₃M₁ | Faster | RBC | 35% |
LDH-3 | H₂M₂ | Intermediate | Brain | 20% |
LDH-4 | H₁M₃ | Slower | Liver, Skeletal muscles | 10% |
LDH-5 | M₄ | Slowest | Liver, Skeletal muscles | 5% |
- Myocardial Infarction (MI) Marker Pattern
- Normal:
- LDH₂ > LDH₁
- MI: (Flipped pattern)
- LDH₁ > LDH₂
Cardiac Enzymes
- Mnemonic: "My Time To Call"
- Earliest Markers (Even before Myoglobin):
- HFABP (Heart Fatty Acid Binding Protein).
- IMA (Ischemia Modified Albumin).
Enzyme / Marker | Start (Rise) | Peak | Fall | Other Notes |
Myoglobin | ~2 hours | Very early | Falls early | • Non-specific • (also in skeletal injury) • Not used for MI diagnosis |
Troponin T/I | 2–4 hours | ~24–48 hours | Falls by 10 days | • Preferred for MI diagnosis • Most used in ER Reinfarction marker: ↳ 20% rise from previous day’s value = reinfarction |
CKMB | 2–4 hours | ~24 hours | Falls by 48–72 hrs | • CKMB → 4 alphabets • → falls before day 4 |
AST (SGOT) | ~12 hours | ~24–36 hours | Falls by 5 days | • Call A → AST |
LDH 1 | 1 day | ~2–3 days | Falls by 10 days | • LDH1 > LDH2 in MI • (Flipping effect) • Normal: LDH2>1 • Heart has highest LDH1 |
Note:
- NT Pro-BNP (Precursor of brain natriuretic peptide):
- Marker of cardiac failure.
Alkaline Phosphatase Isoenzymes:
Isoenzyme | Location | Marker for |
α-1-ALP | Membrane of epithelium of biliary canaliculi | Cholestasis marker |
α-2-ALP (Heat labile) | Hepatic sinusoidal cells | Hepatic Injury |
α-2-ALP (Heat stable) | Placenta | Most stable |
Pre-β-ALP | • β → Bone; • Osteoblast | Marker of bone formation: • Paget's • Vit D Deficiency • Hyperparathyroidism |
Gamma ALP | Intestinal cells | Ulcerative colitis |
Leukocyte ALP | Leukocytes | Leukemia |
- ALPha ALP →
- Alochol → cholestasis
- Liver → Hepatic sinusoids
- Placenta → Stable
- β ALP → Blast Bone → Osteoblast
- G ALP → GIT ALP → UC
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