Transplasma membrane electron transport comes in two flavors.
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.
Lane
Darius J R
DJ
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, VIC 3800, Australia.
Lawen
Alfons
A
D001205:Ascorbic Acid / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism*; D003683:Dehydroascorbic Acid / Q000378:metabolism; D004579:Electron Transport / Q000502:physiology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008954:Models, Biological; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010084:Oxidation-Reduction
D007501:Iron; D009247:NADH, NADPH Oxidoreductases; C014227:ferricyanide reductase; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid