Increased nicotinamide adenine dinucleotide content and synthesis in Plasmodium falciparum-infected human erythrocytes.
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.
Department of Medicine, Harbor-UCLA Medical Center, University of California, Los Angeles School of Medicine, Torrance 90502.
C R
CR
Zerez
E F
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Roth
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S
Schulman
K R
KR
Tanaka
D000818:Animals; D004912:Erythrocytes / Q000032:analysis / Q000378:metabolism / Q000469:parasitology*; D006801:Humans; D009243:NAD / Q000096:biosynthesis / Q000097:blood*; D009249:NADP / Q000032:analysis / Q000378:metabolism; D009535:Nicotinamidase / Q000378:metabolism; D009539:Nicotinic Acids / Q000378:metabolism / Q000494:pharmacology; D010430:Pentosyltransferases / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects / Q000302:isolation & purification*
D009539:Nicotinic Acids; D009243:NAD; D009249:NADP; D010430:Pentosyltransferases; D009535:Nicotinamidase; C021864:nicotinate phosphoribosyltransferase