Affiliations: Department of Biochemistry and Molecular Biology,
School of Biomedical Sciences, Monash University VIC 3800, Australia
Note: [] Address for correspondence: Alfons Lawen, Department of
Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash
University, VIC 3800, Australia. Tel.: +61 3 9905 3711; Fax: +61 3 9905 3726;
E-mail: [email protected]
Abstract: All tested cells possess transplasma membrane electron transfer
(tPMET) systems that are capable of reducing extracellular electron acceptors
at the cost of cytosolic electron donors. In mammals, classically NAD(P)H- and
NADH-dependent systems have been distinguished. The NADH-dependent system has
been suggested to be involved in non-transferrin-bound iron (NTBI) reduction
and uptake. Recently we reported that transplasma membrane
ascorbate/dehydroascorbate cycling can promote NTBI reduction and uptake by
human erythroleukemia (K562) cells (D.J.R. Lane and A. Lawen, J Biol
Chem 28 (2008), 12701–12708). This system, involves i) cellular import
of dehydroascorbate, ii) intracellular reduction of dehydroascorbate to
ascorbate using metabolically-derived reducing equivalents, iii) export of
ascorbate down its concentration gradient, iv) direct reduction of low
molecular weight iron chelates by ascorbate, and v) uptake of iron (II) into
the cell. We here propose the consideration of this system as a novel form of
tPMET which shares with classical enzyme-mediated tPMET systems the net
transfer of reducing equivalents from the cytoplasmic compartment to the
extracellular space, but lacks the involvement of the plasma membrane
oxidoreductases responsible for the latter. Thus, transplasma membrane electron
transfer can and does occur at two mechanistically distinct levels: i)
enzyme-mediated transmembrane electron transfer and ii) transmembrane
metabolite shuttling/cycling.
Keywords: Astrocytes, dehydroascorbate, K562 cells, non-transferrin-bound iron, Vitamin C
DOI: 10.3233/BIO-2009-1072
Journal: BioFactors, vol. 34, no. 3, pp. 191-200, 2009
