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Biochemistry · Protein

Transthyretin (prealbumin) !

Transthyretin carries thyroxine and vitamin A in blood; if its tetramer falls apart, it forms amyloid in the heart and nerves.

Updated 2026-11-01

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Key facts

  • A tetramer of four identical subunits (127 amino acids), made mainly in the liver (and in the choroid plexus for cerebrospinal fluid).
  • Carries thyroxine (T4) in two central channels and retinol bound to retinol-binding protein (RBP).
  • Rate-limiting step of amyloid: the tetramer splits into monomers, which misfold and form fibrils.
  • Variants such as Val30Met (polyneuropathy) or Val122Ile (cardiomyopathy, commoner in people of African ancestry) destabilise the tetramer; normal TTR also forms amyloid in older adults.
  • Called prealbumin because it runs ahead of albumin on electrophoresis; half-life ≈ 2 days.
Also called
Prealbumin, TTR
Genes
TTR
Structure (PDB)
3TCT

Structure

  • Structure 3TCT is normal human transthyretin with tafamidis (code 3MI) in the thyroxine channel; the highlighted site is that channel, where the drug bridges two subunits.
  • The file holds two chains (A, B); the full tetramer is built by crystal symmetry.

Regulation

  • Falls in inflammation (negative acute-phase reactant) and in protein malnutrition.
  • Stabilisers (tafamidis, acoramidis) occupy the T4 site and stop the tetramer from splitting; RNA silencers reduce its synthesis in the liver.

Inhibitors and toxins

  • Tafamidis and acoramidis (tetramer stabilisers)
  • TTR RNA silencers (patisiran, vutrisiran, inotersen)

Clinical notes

  • Hereditary TTR amyloidosis: sensorimotor and autonomic polyneuropathy, cardiomyopathy, gut symptoms.
  • Wild-type TTR amyloidosis (formerly “senile”): cardiomyopathy in older men, often preceded years earlier by bilateral carpal tunnel syndrome.
  • Prealbumin is used as a marker of recent nutritional status, with the caveat that it also falls in inflammation.

Test yourself

Think of the answer, then tap the question to see it.

Which molecules does transthyretin carry?

Thyroxine (T4) and, through retinol-binding protein, vitamin A.

What is the key step for transthyretin to form amyloid?

The tetramer splitting into monomers, which then misfold and aggregate.

How does tafamidis work?

It binds the thyroxine sites and stabilises the tetramer so it does not split into amyloid-forming monomers.

Why is it called prealbumin?

Because on protein electrophoresis it runs slightly ahead of albumin, towards the anode.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: TTR: Transthyretin (human) (UniProt, 2026); TTR gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Transthyretin amyloidosis: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 3TCT: Structure of wild-type TTR in complex with tafamidis (RCSB Protein Data Bank, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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