Transferrin

2022-05-31: reference:

Transferrin #

• The means by which iron initially crosses the BBB.
• Advanced Nutrition and Human Metabolism
  • Carries Iron only in the ferric state, and 1-2 of them. (bound Tf=holo-Tf)
  • The plasma iron pool contains ~3-4 mg of iron bound to transferrin, typically 33% saturated. (100% would imply toxicity)
  • The binding requires an anion, usually bicarbonate, at each binding site.
  • The manjority of iron entering the plasma (~20-25 mg) for distribution by transferrin is contributed from hemoglobin deegradation. The transferrin iron pool turns over 5-8x/day.
  • 7-10 day half life.
• Has two N-linked sugar side chains each with two Sialic Acid residues.

TfR #

• TfR is the transferrin receptor which imports the TF-Fe complex. After binding, it forms a vesicle/endosome with ATP pumps that bring the pH from ~7.4 to 5.5, which facillitates Fe3+ dissociation from Tf, whereby apo-Tf enters the plasma and TfR returns to the membrane.
  • I swear: vesicle = lysosome = endosome = Pax’s “endolysosome”? I see figures that label the endosome as “lysosome”, plain and simple.
    • Deacidification would result in accumulation of holo-TF, I suppose.
  • Pretty sure the resulting free Fe3+ is not part of the labile iron pool, since Fe3+ is insoluble (source: steap3 wikipedia page). It is either reduced by STEAP3, a metalloreductase/ferrireductase or, in certain cells like reticulocytes (immature RBC), shuttled directly into the mitochondria via the endosome making direct contact with the OM. This is nice because it avoids contact with iron as the reticulocytes proceed to use massive amounts of iron.

TfR1: liver and intestinal cells TfR2: preferentially binds diferric