BI5.1-9 | Chemistry & Metabolism of Proteins and Immunology — Summary & Reflection

REFLECT

Test your understanding with these exercises:

1. Draw the four levels of protein structure from memory. For each level, name ONE stabilising force and ONE clinical example of what happens when that level is disrupted.

1. Trace the journey of a piece of chicken protein from your plate to your cells: which enzymes break it down, where does each enzyme act, what are the final absorption products, and where do they go after absorption?

1. Sketch the urea cycle with the 5 enzymes. Mark which steps occur in the mitochondria vs cytoplasm. Why does liver failure cause hyperammonaemia? Why does lactulose help?

1. Compare the three types of jaundice in a table with columns for: cause, unconjugated bilirubin, conjugated bilirubin, urine colour, stool colour. Then explain: why does phototherapy work for neonatal jaundice?

1. Clinical scenario: A 25-year-old patient presents with recurrent painful episodes in the bones and joints. Blood film shows sickle-shaped red cells. (a) What is the molecular defect? (b) Why do the cells sickle under deoxygenation? (c) Why are heterozygous carriers (HbAS) protected against malaria?

KEY TAKEAWAYS

Key takeaways — your study checklist:

1. Amino acids — 20 standard, all L-form, zwitterions at pH 7.4. 9 essential (PVT TIM HALL). Classified by R-group: non-polar, polar, acidic, basic. PKU = can't convert Phe→Tyr.
2. Protein structure — 4 levels: primary (sequence), secondary (α-helix, β-sheet, H-bonds), tertiary (R-group interactions, disulfide bonds), quaternary (multiple subunits). Denaturation = loss of 3D structure.
3. Protein classification — fibrous (collagen, keratin) vs globular (Hb, albumin, enzymes). Simple vs conjugated (glyco-, lipo-, metallo-, chromo-, nucleo-, phospho-). Collagen: triple helix, Gly-X-Y, needs vitamin C (scurvy if deficient).
4. Digestion — stomach (pepsin) → pancreas (trypsin cascade: enterokinase activates trypsinogen) → brush border (aminopeptidases). Absorbed by Na+-dependent transport + PepT1.
5. Plasma proteins — albumin (60%, oncotic pressure, transport), globulins (α1, α2, β, γ), fibrinogen. Electrophoresis: M-spike = myeloma, low albumin + beta-gamma bridging = cirrhosis.
6. Immunoglobulins — Y-shaped, 2H + 2L chains, Fab (antigen-binding) + Fc (effector). IgG (crosses placenta), IgA (secretory), IgM (first response, pentamer), IgE (allergy), IgD (B cell receptor).
7. Ammonia metabolism — toxic NH3 detoxified by urea cycle in liver (5 enzymes, rate-limiting = CPS-I, activated by NAG). Transport forms: glutamine, alanine. Hyperammonaemia → cerebral oedema.
8. Amino acid products — Phe→Tyr (catecholamines, melanin, T3/T4; PKU), Trp→serotonin→melatonin + NAD, Met→SAM (methyl donor; homocystinuria), BCAAs (MSUD). Newborn screening detects these.
9. Haem — porphyrin ring + Fe2+. Synthesis: ALA synthase (rate-limiting, B6). Lead inhibits ALA dehydratase + ferrochelatase. Degradation: bilirubin → conjugated in liver → urobilinogen in gut. Three types of jaundice. Neonatal jaundice → kernicterus risk → phototherapy.
10. Haemoglobin — HbA (α2β2), HbA2 (α2δ2), HbF (α2γ2, high O2 affinity). Derivatives: HbCO (cherry-red, CO), MetHb (chocolate-brown, Fe3+), HbA1c (diabetes monitoring). Variants: HbS (sickle cell, β6 Glu→Val), thalassaemias (reduced chain production).