Fick’s law and the mammalian lung

Every good gas exchange surface shares three properties: a large surface area, a thin exchange surface (short diffusion distance) and a steep concentration difference maintained by ventilation and blood flow.

In the lung, roughly 300–500 million alveoli provide a surface area of about 70 m². The barrier is just two squamous cells thick (alveolar epithelium + capillary endothelium), under 1 µm. Ventilation replaces alveolar air and the dense capillary network carries oxygenated blood away, so the concentration gradient is maintained.

Your turn — Fick’s law

The fluid-mosaic membrane and transport

The fluid-mosaic model (Singer & Nicolson): a phospholipid bilayer — hydrophilic phosphate heads out, hydrophobic fatty-acid tails in — studded with proteins. Cholesterol sits between the tails, regulating fluidity. Glycoproteins and glycolipids act in cell recognition. It is a model: an interpretation of freeze-fracture and labelling data, not a photograph.

• Simple diffusion — small, non-polar molecules (O₂, CO₂) pass straight through the bilayer, down the gradient. Passive.
• Facilitated diffusion — polar molecules and ions pass through channel or carrier proteins, down the gradient. Passive.
• Osmosis — net movement of free water molecules through a partially permeable membrane, from a less negative to a more negative water potential.
• Active transport — a carrier protein moves a substance against its gradient, using ATP.
• Endocytosis / exocytosis — bulk transport in vesicles; both require ATP.

Core practical 3: investigate membrane permeability using beetroot. Heat or ethanol disrupts the bilayer and denatures membrane proteins, so red betalain pigment leaks out — measured with a colorimeter.

Does it need ATP?

Tap a process, then tap the correct group.

DNA and RNA structure

A mononucleotide = a pentose sugar (deoxyribose or ribose) + a phosphate group + a nitrogenous base. Nucleotides join by condensation to give a sugar–phosphate backbone linked by phosphodiester bonds.

• DNA is a double helix of two antiparallel strands (5′→3′ and 3′→5′).
• Complementary base pairing: A–T (two hydrogen bonds), C–G (three hydrogen bonds). A purine always pairs with a pyrimidine, keeping the helix a constant width.
• RNA is single-stranded, has ribose, and uses uracil in place of thymine.

Many hydrogen bonds together make DNA stable, yet each one is individually weak — so the strands can be separated for replication and transcription. That is the whole trick of the molecule.

Transcription, translation and the code

Transcription (in the nucleus): DNA helicase unwinds the helix; RNA polymerase reads the template (antisense) strand 3′→5′ and builds a complementary mRNA molecule. The coding (sense) strand has the same base sequence as the mRNA, but with T instead of U.

Translation (on a ribosome): mRNA binds to the ribosome; a tRNA with the complementary anticodon brings the amino acid specified by each codon. The ribosome catalyses formation of a peptide bond and moves on one codon, until it reaches a stop codon.

The code is triplet, non-overlapping, degenerate (most amino acids have more than one codon — so some substitutions are silent) and effectively universal, which is why genes can be transferred between species.

Your turn — from bases to amino acids

Match the molecular players

Tap a job on the left, then the molecule that does it.

Protein structure — four levels

An amino acid has a central carbon bonded to an amine group (–NH₂), a carboxyl group (–COOH), a hydrogen and a variable R group. Amino acids join by condensation, forming a peptide bond.

• Primary — the sequence of amino acids. This is coded for by the gene and determines every level above it.
• Secondary — α-helix or β-pleated sheet, held by hydrogen bonds between the C=O and N–H of the backbone.
• Tertiary — the overall 3-D fold, held by hydrogen bonds, ionic bonds, disulfide bridges (between cysteine R groups) and hydrophobic interactions.
• Quaternary — two or more polypeptides, e.g. haemoglobin’s four chains plus four haem prosthetic groups.

Change one amino acid in the primary structure and the R-group interactions change, so the tertiary structure — and therefore the function — can be destroyed. That is exactly what happens in cystic fibrosis and sickle-cell anaemia.

Enzyme action and inhibition

Enzymes are globular proteins that act as biological catalysts: they lower the activation energy of a reaction. The substrate binds the active site, whose shape is complementary to it, forming an enzyme–substrate complex.

The modern model is induced fit: the active site is flexible and moulds around the substrate as it binds, straining its bonds and so lowering the activation energy. Specificity comes from the tertiary structure of the active site.

• Competitive inhibition — the inhibitor is a similar shape to the substrate and binds the active site. Its effect is reduced by increasing substrate concentration; V_max is unchanged.
• Non-competitive inhibition — the inhibitor binds elsewhere (an allosteric site), changing the active site’s shape. Adding substrate does not reverse it; V_max falls.

Intracellular enzymes (e.g. catalase) work inside cells; extracellular enzymes (e.g. amylase, trypsin) are secreted. Core practical 4 investigates the effect of an enzyme concentration or an inhibitor on rate.

Which inhibitor?

Semi-conservative replication and mutation

DNA replication: DNA helicase breaks the hydrogen bonds and unwinds the helix. Free DNA nucleotides pair with the exposed bases, and DNA polymerase catalyses phosphodiester bonds, working only 5′→3′ — so one strand is made continuously (leading) and the other in fragments (lagging), joined by DNA ligase.

Meselson & Stahl (1958) grew E. coli in heavy ¹⁵N, then switched to ¹⁴N. After one generation all the DNA was of intermediate density (ruling out conservative replication); after two generations there was a 1:1 mix of intermediate and light DNA (ruling out dispersive). Only semi-conservative replication fits both results.

Mutations arise from errors in replication. A substitution may be silent (the code is degenerate), missense or nonsense. A deletion or insertion of a number of bases not divisible by three causes a frameshift, changing every codon downstream.

CF — one gene, many consequences

The CFTR protein is a chloride ion channel in the cell-surface membrane of epithelial cells. The commonest mutation, Δ508, deletes three bases, so one amino acid (phenylalanine) is missing. The protein misfolds and is destroyed before it reaches the membrane.

With no working channel, Cl⁻ is not secreted, so water does not follow by osmosis. The mucus layer becomes thick and sticky:

• Lungs — mucus blocks the airways and traps bacteria: repeated infection and lung damage.
• Pancreas — the duct is blocked, so digestive enzymes cannot reach the gut: poor digestion and weight gain.
• Reproductive system — the vas deferens or cervix is blocked: reduced fertility.

Your turn — inheritance probability

Your turn — chi-squared

Interpreting your χ²

Genetic screening

Screening identifies carriers or affected embryos. Methods include amniocentesis (~15–16 weeks, ~1 % miscarriage risk), chorionic villus sampling (~11 weeks, slightly higher risk, but an earlier result) and pre-implantation genetic diagnosis (PGD) during IVF, which avoids the question of terminating a pregnancy but is expensive and involves discarding embryos.

Issues to discuss, not just list: reliability of the result and the impact of a false positive; whether a positive result creates pressure to terminate; confidentiality and possible discrimination by insurers or employers; and the slippery slope towards selecting for non-medical traits.

The big ideas to know

You have covered the whole of SNAB Topic 2. Press Finish to see your score.