Effects of nine synthetic putative metabolites of primaquine on activity of the hexose monophosphate shunt in intact human red blood cells in vitro

Biochemical Pharmacology
J K BairdC J Canfield

Abstract

Suspensions of washed human red blood cells were treated with nine synthetic putative metabolic derivatives of primaquine (PQ'), and their individual effects on activity of the hexose monophosphate shunt (HMS) were quantitated by radiometric analysis of 14CO2 from [14C] glucose. The most potent HMS stimulant was 5-hydroxy-6-methoxy-8-aminoquinoline (5H6MQ), which caused 10-fold elevation of HMS activity at an estimated concentration of 0.004 mM. Ten millimolar primaquine (PQ) was required to achieve the same effect. Thus, 5H6MQ was approximately 2500-fold more reactive with the HMS than PQ. Other analogs achieved less than 0.4- to 154-fold increases in HMS reactivity. Patterns of effects on HMS activity indicated that 5-hydroxylation and/or N-dealkylation of PQ strongly enhanced HMS reactivity. In contrast, none of the putative metabolites of PQ activated the proteolytic system known to degrade oxidized protein in red cells, indicating that stimulation of the HMS by the PQ analogs was not related to an injurious oxidative stress. Red cells pretreated with 1.0 mM N-ethylmaleimide (NEM) or with 1.0% (w/v) sodium nitrite to cause glutathione sulfhydryl blockage and conversion of red cell hemoglobin to methemoglobin (metHb), respec...Continue Reading

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Aug 21, 2013·Parasitology·Alice S ButterworthKatharine R Trenholme
May 1, 2012·Malaria Journal·Nicholas M DouglasRic N Price
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