SN4 SHORT NOTE 5M ★ High-yield

Describe the structure and biosynthesis of collagen. Add a note on its disorders.

Biochemistry · 1st Professional — Pre-Clinical

Definition

Collagen = the most abundant protein in the human body, forming 25–30% of total body protein; the chief structural protein of the extracellular matrix.

Structure

Triple helix — three left-handed polypeptide (α) chains wound into a right-handed superhelix
Repeating sequence (Gly–X–Y)n, where X is often proline and Y often hydroxyproline
Glycine occupies every third position — it is the only amino acid small enough to fit the crowded interior of the helix
Rich in proline and hydroxyproline; contains hydroxylysine; lacks tryptophan and cysteine
Held together by hydrogen bonds involving hydroxyproline

Types

Type	Location
Type I	Skin, bone, tendon, cornea — the commonest (90%)
Type II	Cartilage, vitreous humour
Type III	Reticulin — blood vessels, fetal skin, granulation tissue
Type IV	Basement membrane — does not form fibrils
Type VII	Anchoring fibrils of skin

Biosynthesis

Preprocollagen → signal peptide removed → hydroxylation of proline and lysine — needs vitamin C, Fe2+, α-ketoglutarate, O2 → glycosylation of hydroxylysine → Triple helix forms → procollagen, secreted → Procollagen peptidase removes the terminal extensions → tropocollagen → Self-assembly into fibrils → lysyl oxidase (needs copper) forms cross-links → mature collagen

Two vitamin and mineral dependencies matter clinically — vitamin C for hydroxylation and copper for cross-linking

Disorders of Collagen

Disorder	Defect	Features
Scurvy	Vitamin C deficiency → no hydroxylation	Bleeding gums, perifollicular haemorrhage, poor wound healing, old scars breaking down
Osteogenesis imperfecta	Type I collagen — usually a glycine substitution	Brittle bones, blue sclerae, deafness, dentinogenesis imperfecta
Ehlers–Danlos syndrome	Various — types I, III, V; lysyl hydroxylase or procollagen peptidase	Hyperextensible skin, hypermobile joints, vascular rupture
Menkes disease	Copper transport defect → lysyl oxidase fails	Kinky hair, arterial tortuosity, neurodegeneration
Alport syndrome	Type IV collagen	Haematuria, renal failure, sensorineural deafness
Goodpasture syndrome	Antibodies to type IV collagen	Glomerulonephritis with pulmonary haemorrhage

Applied Aspects

Urinary hydroxyproline is a marker of collagen turnover — raised in Paget disease, hyperparathyroidism and bone metastases
Elastin is the complementary protein — rich in glycine and proline but not hydroxylated, cross-linked by desmosine, and confers recoil rather than tensile strength
Gelatin is denatured collagen — a poor-quality dietary protein, lacking tryptophan entirely
Collagen provides tensile strength, which is why its disorders present with fragility — of bone, skin, vessels or basement membrane, depending on the type affected

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