Evidence for the extracellular reduction of α-lipoic acid by Leishmania donovani promastigotes: a transplasma membrane redox system

Abstract

Leishmania donovani cells, capable of reducing certain electron acceptors with redox potentials at pH 7.0 down to -290 mV, outside the plasma membrane, can reduce the oxidised form of alpha-lipoic acid. alpha-Lipoic acid has been used as natural electron acceptor probe for studying the mechanism of transplasma membrane electron transport. Transmembrane alpha-lipoic acid reduction by Leishmania was not inhibited by mitochondrial inhibitors as azide, cyanide, rotenone or antimycin A, but responded to hemin, modifiers of sulphhydryl groups and inhibitor of glycolysis. The protonophores carbonyl cyanide chlorophenylhydrazone and 2,4-dinitrophenol showed inhibition of alpha-lipoic acid reduction. This transmembrane redox system differs from that of mammalian cells in respect to its sensitivity of UV irradiation and stimulation by diphenylamine. Thus a naphthoquinone coenzyme appears to be involved in alpha-lipoic acid reduction by Leishmania cells.

A defined medium for Leishmania culture allows definition of essential amino acids

“…Lipoic acid and its reduced form, dihydrolipoic acids, are highly reactive antioxidants which scavenge reactive oxygen species such as superoxide radicals, hydroxyl radicals, hypochlorous acid, peroxyl radicals, singlet oxygen, chromanoxyl radicals of vitamin E, and ascorbyl radicals of vitamin C [85,86]. Lipoic acid, additionally, is an essential co-factor in several multienzyme complexes, such as pyruvate dehydrogenase (PDH), 2-oxoglutarate dehydrogenase (OGDH), and branched-chain 2-oxo acid dehydrogenase (BCDH) complexes [87].…”