A putative glutathione peroxidase gene (Swiss-Prot accession number Z 68200) of 
Plasmodium falciparum, the causative agent of tropical malaria, was expressed in 
Escherichia coli and purified to electrophoretic homogeneity. Like phospholipid 
hydroperoxide glutathione peroxidase of mammals, it proved to be monomeric. It 
was active with H(2)O(2) and organic hydroperoxides but, unlike phospholipid 
hydroperoxide glutathione peroxidase, not with phosphatidylcholine 
hydroperoxide. With glutathione peroxidases it shares the ping-pong mechanism 
with infinite V(max) and K(m) when analyzed with GSH as substrate. As a 
homologue with selenocysteine replaced by cysteine, its reactions with 
hydroperoxides and GSH are 3 orders of magnitude slower than those of the 
selenoperoxidases. Unexpectedly, the plasmodial enzyme proved to react faster 
with thioredoxins than with GSH and most efficiently with thioredoxin of P. 
falciparum (Swiss-Prot accession number 202664). It is therefore reclassified as 
thioredoxin peroxidase. With plasmodial thioredoxin, the enzyme also displays 
ping-pong kinetics, yet with a limiting K(m) of 10 microm and a k(1)' of 0.55 
s(-)1. The apparent k(1)' for oxidation with cumene, t-butyl, and hydrogen 
peroxides are 2.0 x 10(4) m(-1) s(-1), 3.3 x 10(3) m(-1) s(-1), and 2.5 x 10(3) 
m (-1) s(-1), respectively. k(2)' for reduction by autologous thioredoxin is 5.4 
x 10(4) m(-1) s(-1) (21.2 m(-1) s(-1) for GSH). The newly discovered enzymatic 
function of the plasmodial gene product suggests a reconsideration of its 
presumed role in parasitic antioxidant defense.