# Haemoglobin Structure and Function > Haemoglobin structure and function for FMGE Biochemistry: T and R states, Bohr effect, 2,3-BPG, HbF affinity and carboxyhaemoglobin. - Canonical URL: https://prepelephant.com/topics/fmge/biochemistry/haemoglobin-structure-function-fmge - Exam / course: FMGE · Subject: Biochemistry - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Haemoglobin Structure and Function", PrepElephant, https://prepelephant.com/topics/fmge/biochemistry/haemoglobin-structure-function-fmge ## Direct answer The sigmoid shape of the haemoglobin-oxygen dissociation curve is the visible signature of cooperativity: binding of the first oxygen to a T (tense, deoxy) subunit breaks salt bridges and flips the tetramer toward the R (relaxed) state, raising the affinity of the remaining haems — steeper than myoglobin's hyperbola. Haemoglobin A (α2β2, about 97% of adult haemoglobin) carries four haems (protoporphyrin IX chelating ferrous iron), transporting up to four oxygens with P50 near 26-27 mmHg. Three ligands tune it: hydrogen ion and carbon dioxide (the Bohr effect) shift it right to unload in acidic, CO2-rich tissues; 2,3-bisphosphoglycerate binding the β chains shifts right too; foetal haemoglobin (α2γ2) binds 2,3-BPG poorly, so its curve sits left, pulling oxygen from maternal blood. ## What you must remember - **Normal fractions:** HbA 97%, HbA2 (α2δ2) about 2-2.5%, HbF below 1% in adults — HbA2 raised in β-thalassaemia trait, HbF raised in thalassaemia major and hereditary persistence of foetal haemoglobin. - **Biochemistry of unloading:** metabolically active tissues deliver H+ and CO2 (carried as bicarbonate via the chloride shift and carbamino compounds), protonating haemoglobin and releasing oxygen — the Bohr effect couples perfusion to metabolism. - **2,3-BPG rules:** raised at altitude, in chronic hypoxia and anaemia (right shift, better unloading); reduced in stored blood (left shift, poor initial unloading after transfusion). - **Carbon monoxide:** binds haem iron with about 200-250 times oxygen's affinity, produces a cherry-red patient with normal PaO2 and falsely reassuring pulse oximetry, and shifts the remaining sites' curve left. - **Methaemoglobinaemia:** ferric (Fe3+) haemoglobin cannot carry oxygen and shifts the curve left — chocolate-brown blood, cyanosis unresponsive to oxygen, treated with methylene blue (which recycles NADH methaemoglobin reductase); nitrates, dapsone and local anaesthetics are triggers. - **Cooperativity quotient:** Hill coefficient near 2.8 for haemoglobin (1.0 for myoglobin) — the number that quantifies sigmoidicity in viva discussions. - **Glycation:** HbA1c forms at the N-terminal valine of the β chain and reports the preceding 8-12 weeks of glycaemia. - **Thalassaemia versus haemoglobinopathy:** reduced chain synthesis (quantitative) versus abnormal chain structure (qualitative) — sickle and HbE versus α- and β-thalassaemia. ## A worked case: a family poisoned by a generator After a cold night, four members of a household are found confused with headaches; a pressure generator had run indoors. Blood gas shows a normal PaO2, but carboxyhaemoglobin is 28% in the most affected. The logic: carbon monoxide outcompetes oxygen for haem binding by two orders of magnitude, so oxygen content collapses while tension looks fine; the left-shifted residual curve starves tissues of the little oxygen aboard; the pulse oximeter reads near-normal because it cannot distinguish carboxyhaemoglobin from oxyhaemoglobin — a saturation gap between co-oximetry and pulse oximetry is the bedside tell. Treatment is 100% oxygen (halving the half-life from about 4-5 hours on room air to about 1 hour) and hyperbaric oxygen for coma, seizures, pregnancy or levels above about 25%. Cyanide poisoning is the companion case: there tissues cannot use oxygen, so venous oxygen is high and lactate rises — one blocks carriage, the other blocks consumption. ## Where students slip Bohr and 2,3-BPG are both "right shifts" but by different mechanisms — protons stabilise the T state by salt bridges, while 2,3-BPG is a T-state ligand bound in the central cavity between β chains; stating the shared direction without the mechanism loses the discriminating mark. Second, HbF's left shift is reasoned as "more affinity for oxygen because it is foetal" without the 2,3-BPG-poor γ chain explanation, which is what the examiner wants. Third, stored blood's left shift is forgotten in transfusion questions — a freshly transfused patient may have adequate saturation yet poor tissue delivery for hours. Fourth, cyanosis thresholds differ: methaemoglobin causes chocolate cyanosis at far lower concentrations than reduced haemoglobin (which needs about 5 g/dL). Fifth, the PaO2 in CO poisoning is normal because it measures dissolved oxygen tension, not content — anchoring on "the blood gas was fine" delays the diagnosis. ## Frequently asked questions ### Why is the haemoglobin oxygen curve sigmoid? Binding of each oxygen converts the T state to the R state and increases the affinity of remaining subunits — positive cooperativity, with a Hill coefficient near 2.8. ### What is the Bohr effect and its physiological purpose? Hydrogen ions and carbon dioxide shift the curve right, letting haemoglobin unload oxygen precisely in the acidic, CO2-rich tissues that need it most. ### Why does foetal haemoglobin have a higher oxygen affinity? Its γ chains bind 2,3-bisphosphoglycerate poorly, producing a left-shifted curve that extracts oxygen from maternal blood across the placenta. ### How does carbon monoxide deceive the blood gas and oximeter? It leaves dissolved oxygen tension normal while collapsing oxygen content, and pulse oximetry cannot distinguish carboxyhaemoglobin from oxyhaemoglobin. ### How is methaemoglobinaemia treated? Methylene blue, which uses the NADH-dependent reductase pathway to reduce ferric iron back to ferrous — avoiding further oxidant drugs.