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#iron transport

3 public questions tagged with this topic.

Animal Tissue Culture 1

Which component provides iron transport in serum?

Iron necessity stems from essential cofactor roles in fundamental enzymes: ribonucleotide reductase small subunit R2 contains diferric tyrosyl radical centre essential for reducing ribonucleoside diphosphate to deoxyribonucleotide required for DNA replication and repair, cytochrome c oxidase complex IV contains heme a3 plus copper facilitating electron transport to oxygen, and aconitase iron-sulfur cluster catalyzing tricarboxylic acid cycle. Free ferric iron Fe3+ precipitates as insoluble Fe(OH)3 at neutral pH solubility product extremely low 10^-38, and participates in Fenton reaction Fe2+ p

Ref: Crichton Iron Metabolism 2016 transferrin Fe3+ transport 80 kDa; Alberts MBoC TfR1 clathrin endocytosis ribonucleotide reductase.

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Protein Sorting and Trafficking

What happens when the transferrin receptor is mutated and cannot bind Fe³⁺ at acidic pH?

Iron uptake in proliferating cells depends on transferrin receptor mediated endocytosis tightly coupled to endosomal acidification. At extracellular pH 7.4 holo transferrin carrying two ferric ions binds transferrin receptor 1 homodimer with nanomolar affinity, clusters via AP2 clathrin adaptor and internalizes into early endosomes. Vacuolar ATPase acidifies lumen to about pH 5.5, protonation of transferrin histidines and nearby receptor residues induces conformational opening of transferrin lobes, reducing Fe3+ affinity by orders of magnitude and releasing ferric iron while apo transferrin re

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 13: Endocytosis and Transferrin Iron Transport.

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Protein Sorting and Trafficking

During receptor-mediated endocytosis of iron, Fe³⁺ is transported into cells via:

Vertebrates transport ferric iron safely via transferrin family to avoid oxidative Fenton radical damage and precipitation. Hepatocytes secrete apo-transferrin 80 kDa bilobed glycoprotein serum loads two Fe3+ each coordinated synergistically bidentate carbonate anion plus four protein ligands two tyrosines histidine aspartate each lobe producing salmon pink complex termed ferrotransferrin diferric transferrin. Doubly loaded species binds transferrin receptor TfR1 homodimer dissociation constant 1-10 nM neutral pH versus 50-fold lower affinity monoferric negligible apo providing selection iron

Ref: Lodish et al., MCB Figure 14-29: Ferrotransferrin carries Fe3+ for uptake via transferrin receptor.

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