Unit Converter
Hemoglobin tetramer
(Functional Hemoglobin Molecule - α₂β₂ Structure Responsible for Oxygen Transport)
Synonyms
- Hemoglobin tetramer
- Hb tetramer
- Functional hemoglobin
- α₂β₂ hemoglobin
- Adult hemoglobin (HbA)
- Oxygen-binding hemoglobin complex
- Complete hemoglobin molecule
Units of Measurement
- mmol/L
- µmol/L
- g/L
- g/dL
- g/100 mL
- g%
- mg/mL
Molecular Weight
Functional hemoglobin tetramer (HbA): ~64,500 Da
Key Unit Conversions
Using MW ~64.5 kDa:
1 g/L = 0.0155 mmol/L
1 mmol/L = 64.5 g/L
1 µmol/L = 0.0645 g/L
1 g/dL = 10 g/L
g% = g/dL
1 mg/mL = 1 g/dL
Description
The hemoglobin tetramer is the fully functional oxygen-carrying protein in red blood cells.
Each tetramer consists of:
- 2 α-globin chains
- 2 β-globin chains
- 4 heme groups (Fe²⁺)
- Ability to bind 4 oxygen molecules
Tetrameric structure is crucial for:
- Oxygen transport
- Cooperative binding
- Efficient gas exchange
- Acid–base buffering
- CO₂ transport
This is the true physiological form of hemoglobin in circulation.
Physiological Role
1. Oxygen Transport
Tetramers bind oxygen in the lungs and release it in tissues.
2. Cooperative Binding (Key Feature)
Binding of one O₂ increases affinity at other sites → sigmoidal O₂ dissociation curve.
3. CO₂ Transport
Forms carbaminohemoglobin; participates in the Haldane effect.
4. Acid–Base Regulation
Buffers hydrogen ions via histidine residues.
5. Maintenance of RBC Function
Tetramer stability prevents oxidative stress and hemolysis.
Clinical Significance
Abnormal Tetramer Formation Leads to Disease
1. Hemoglobinopathies
Tetramer composition affects function:
- HbS (Sickle cell disease): β⁶ Glu→Val substitution → polymerization
- HbC, HbD, HbE variants
- HbSC disease
These disorders stem from altered tetramer stability or function.
2. Thalassemias
Imbalanced globin synthesis:
- α-thalassemia → excess β chains → HbH (β₄ tetramers)
- β-thalassemia → excess α chains → precipitates
Tetramer abnormalities cause hemolysis and ineffective erythropoiesis.
3. Methemoglobinemia
Iron oxidation (Fe³⁺) within tetramers → impaired oxygen delivery.
4. Carboxyhemoglobin Formation
CO binds tetramers with high affinity → CO poisoning.
5. Hemolytic Anemias
Tetramer breakdown releases:
- Dimers
- Monomers
- Free heme → oxidative injury
6. RBC Storage Lesions
Stored blood shows increased tetramer dissociation → aging effects.
Reference Intervals
Tetrameric hemoglobin concentration is identical to total hemoglobin, because all physiologic Hb is tetrameric.
Adults
| Group | Hemoglobin (Tetrameric) |
| Men | 130–170 g/L (13.0–17.0 g/dL) |
| Women | 120–150 g/L (12.0–15.0 g/dL) |
Children
- Newborn: 140–200 g/L
- Infant: 100–180 g/L
- Older child: approaches adult values
Critical Values
- <70 g/L (7 g/dL): severe anemia, risk of hypoxia
- >200 g/L (20 g/dL): hyperviscosity, thrombosis
Diagnostic Uses (Applied to Tetrameric Hemoglobin)
1. Diagnosis of Anemia
Low tetramer concentration directly indicates RBC loss or dysfunction.
2. Detect Hemoglobin Variants
Tetramer abnormalities detected by:
- Electrophoresis
- HPLC
- Mass spectrometry
- Genetic testing
3. Oxygen-Carrying Disorders
Structural changes in tetramers → abnormal oxygen affinity.
4. CO or Methemoglobin Poisoning
Tetramer modifications alter gas-binding properties:
- Carboxyhemoglobin
- Methemoglobin
5. Monitoring Therapy
- Iron therapy
- Erythropoiesis-stimulating agents
- Transfusions
- Sickle cell therapy (hydroxyurea → ↑HbF tetramers)
Analytical Notes
- Tetramer concentration is clinically identical to total Hb
- Measured via automated analyzers (photometric)
- Do not confuse with monomer/dimer fractions seen in research
- Stability of tetramer affected by pH, temperature, storage
Clinical Pearls
- Nearly all circulating hemoglobin is tetrameric - monomers only appear after hemolysis.
- HbA tetramer (α₂β₂) is the dominant adult form (~95%).
- HbF (α₂γ₂) tetramers have higher oxygen affinity, important in pregnancy.
- Hb breakdown → free heme → oxidative injury → triggers haptoglobin response.
- Tetramer structure underlies the oxygen dissociation curve — foundational for respiratory physiology.
Interesting Fact
The tetrameric structure of hemoglobin is responsible for the sigmoidal oxygen dissociation curve, enabling both high oxygen loading in lungs and efficient unloading in tissues - a hallmark of evolutionary optimization.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Hemoglobin structure & function.
- WHO Hemoglobin Criteria for Anemia.
- AABB & BCSH Guidelines - Hemoglobinopathies.
- Mayo Clinic Laboratories - Hemoglobin analysis.
- ARUP Consult - Hemoglobin Variants.
- NIH Hemoglobin Structure Database.