(a)(i) Explain sigmoidal nature of oxygen dissociation curve for hemoglobin. (10 marks) (a)(ii) Describe differences between…

The three parts illustrate how molecular interactions produce physiological function, defence and body patterning.

Sigmoidal oxygen dissociation curve. Hemoglobin is an α2β2 tetramer. Binding of the first O2 molecule is weak because deoxygenated Hb is in the low-affinity T-state; this binding induces conformational changes at the α1β2 interfaces that shift the tetramer toward the high-affinity R-state. The R-state increases affinity of the remaining subunits, so O2 binding is cooperative. This produces a sigmoidal curve rather than a hyperbolic one, with a Hill coefficient of about 2.8–3.0. The sigmoid shape is physiologically useful because at high pulmonary pO2 Hb becomes nearly saturated, while at lower tissue pO2 the cooperative transition makes it release O2 efficiently over a narrow pO2 range. The steep middle portion means that a small fall in tissue pO2 causes a large fall in saturation, while pulmonary Hb remains highly saturated. 2,3-BPG binds preferentially to the deoxygenated T-state, stabilizes it and lowers O2 affinity, thereby promoting unloading in metabolically active tissues.

Adult and fetal hemoglobin. Adult HbA is α2β2; fetal HbF is α2γ2. The γ chains differ from β chains in several residues; a common γ-chain polymorphism at position 136 is glycine in Gγ versus alanine in Aγ. More importantly for O2 affinity, γ-chain substitutions reduce 2,3-BPG binding, especially because histidine at β82 is replaced by serine in γ chains. Deoxygenated HbF still adopts a T-state; the reduced 2,3-BPG binding shifts the T–R equilibrium toward R relative to HbA, giving HbF a higher O2 affinity and a lower P50. In the placenta, maternal HbA releases O2 while fetal HbF loads O2 from maternal blood, facilitating transfer to the fetus. This difference in affinity creates a favourable O2 gradient across the placenta. Persistence of HbF is clinically important: in β-thalassaemia it can compensate for defective β chains, and in sickle-cell disease it interferes with HbS polymerization, reducing sickling.

Cytotoxic T-cell mechanism. A cytotoxic T lymphocyte recognizes a specific peptide presented on MHC class I by its TCR, with co-stimulatory signals. This recognition identifies virus-infected or tumour cells. Once engaged, the TCR signal promotes granule mobilization and polarization toward the target cell. Perforin forms pores in the target membrane, allowing granzymes to enter and activate caspases, causing apoptosis. A second pathway is Fas–FasL mediated apoptosis: FasL on the CTL binds Fas on the target, recruiting FADD and caspase-8 to initiate programmed cell death. Apoptosis is non-inflammatory, limiting collateral tissue damage. The CTL survives, proliferates and can form long-lived memory cells that respond rapidly on re-exposure.

Homeotic genes. Homeotic genes are selector genes that assign identity to body segments or regions. In vertebrates they are Hox genes, organized in clusters, and they obey colinearity: gene order on the chromosome corresponds to the order of expression along the anteroposterior axis and to developmental timing. In the chick, Hox genes are expressed in overlapping domains along the neural tube and somites, providing a combinatorial code that specifies cranial, cervical, thoracic and lumbar identities. The anterior-to-posterior expression order ensures each segment receives the correct Hox code. For example, Hoxb-1 is expressed in an anterior hindbrain/cervical domain, while Hoxc-6 is expressed more posteriorly in thoracic regions, helping pattern the neck and trunk. By regulating downstream target genes, Hox proteins determine segment-specific structures such as vertebrae and ribs. Their conservation from Drosophila to vertebrates shows that Hox colinearity is a fundamental mechanism of AP axis formation.

Thus, cooperative Hb conformation, CTL recognition and Hox colinearity each convert molecular interactions into organism-level function: efficient gas exchange, targeted immune killing and correct body patterning.