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CR Zerez, EF Roth , S Schulman and KR Tanaka
Department of Medicine, Harbor-UCLA Medical Center, University of
California, Los Angeles School of Medicine, Torrance 90502.
Plasmodium falciparum-infected red blood cells (RBCs) are characterized by
increases in the activity of glycolytic enzymes. Because nicotinamide
adenine dinucleotide (NAD) and NAD phosphate (NADP) are cofactors in the
reactions of glycolysis and pentose phosphate shunt, we have examined NAD
and NADP content in P. falciparum-infected RBCs. Although NADP content was
not significantly altered, NAD content was increased approximately 10-fold
in infected RBCs (66% parasitemia) compared with uninfected control RBCs.
To determine the mechanism for the increase in NAD content, we examined the
activity of several NAD biosynthetic enzymes. It is known that normal human
RBCs make NAD exclusively from nicotinic acid and lack the capacity to make
NAD from nicotinamide. We demonstrate that infected RBCs have readily
detectable nicotinamide phosphoribosyltransferase (NPRT), the first enzyme
in the NAD biosynthetic pathway that uses nicotinamide, and abundant
nicotinamide deamidase, the enzyme that converts nicotinamide to nicotinic
acid, thereby indicating that infected RBCs can make NAD from nicotinamide.
In addition, infected RBCs have a threefold increase in nicotinic acid
phosphoribosyltransferase (NAPRT), the first enzyme in the NAD biosynthetic
pathway that uses nicotinic acid. Thus, the increase in NAD content in P
falciparum-infected RBCs appears to be mediated by increases in NAD
synthesis from both nicotinic acid and nicotinamide.
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| Copyright © 1990 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||