Lead, ALAD and Malaria - Response to comment by Ingvar Bergdahl

摘要

We thank Dr. Bergdahl for pointing out the fact that inhibition of the activity of ALAD has a potential of decreasing the success of Plasmodium parasites during the erythrocyte stage in human host (Bergdahl, 2009). It should be noted in this regard that a blood lead concentration of 15pg/dL can result in a 50% inhibition of ALAD activity (Astrin et al., 1987), and that over 80% of the intraerythrocytic lead is bound to ALAD (Bergdahl et al., 1997). Dr. Bergdahl did the pioneering work on the binding of lead to 8-aminolevulinate dehydratase (ALAD) and the metabolic consequences, and his letter provides another biological mechanism in support of our observation on the role of lead exposure in moderating the development of malaria in Plasmo-dium-infected individuals (Nriagu et al., 2008). It should, however, be noted that the claim that malaria parasites somehow co-opt the heme biosynthetic machinery of the host's erythrocyte, thereby inheriting enzymes that include (ALAD), coprogen oxidase (CPO) and ferrochelatase remains controversial (Sato and Wilson, 2002; Sato et al., 2004; Sazawal et al., 2006). All the eight enzymes required for de novo biosynthesis of heme have been documented in both the mitochondrion and plastid of the human malaria parasite Plasmodium falciparum (Sato et al., 2004).