Hemoglobin metabolism in the malaria parasite Plasmodium falciparum

被引:629
作者
Francis, SE
Sullivan, DJ
Goldberg, DE
机构
[1] HOWARD HUGHES MED INST, DEPT MED, ST LOUIS, MO 63110 USA
[2] BARNES JEWISH HOSP, ST LOUIS, MO 63110 USA
关键词
protease; plasmepsin; falcipain; heme; quinoline;
D O I
10.1146/annurev.micro.51.1.97
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Hemoglobin degradation in intraerythrocytic malaria parasites is a vast process that occurs in an acidic digestive vacuole. Proteases that participate in this catabolic pathway have been defined. Studies of protease biosynthesis have revealed unusual targeting and activation mechanisms. Oxygen radicals and heme are released during proteolysis and must be detoxified by dismutation and polymerization, respectively. The quinoline antimalarials appear to act by preventing sequestration of this toxic heme. Understanding the disposition of hemoglobin has allowed identification of essential processes and metabolic weakpoints that can be exploited to combat this scourge of mankind.
引用
收藏
页码:97 / 123
页数:27
相关论文
共 161 条
[1]   LOCALIZATION OF ACID PHOSPHATASE ACTIVITY IN PLASMODIUM-BERGHEI AND P-GALLINACEUM - ELECTRON MICROSCOPIC OBSERVATION [J].
AIKAWA, M ;
THOMPSON, PE .
JOURNAL OF PARASITOLOGY, 1971, 57 (03) :603-&
[2]   FEEDING MECHANISM OF AVIAN MALARIAL PARASITES [J].
AIKAWA, M ;
HEPLER, PK ;
HUFF, CG ;
SPRINZ, H .
JOURNAL OF CELL BIOLOGY, 1966, 28 (02) :355-+
[3]  
AISSI E, 1983, COMP BIOCH PHYSL B, V7, P559
[4]   REACTION OF ANTIMALARIAL ENDOPEROXIDES WITH SPECIFIC PARASITE PROTEINS [J].
ASAWAMAHASAKDA, W ;
ITTARAT, I ;
PU, YM ;
ZIFFER, H ;
MESHNICK, SR .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (08) :1854-1858
[5]   EFFECTS OF ANTIMALARIALS AND PROTEASE INHIBITORS ON PLASMODIAL HEMOZOIN PRODUCTION [J].
ASAWAMAHASAKDA, W ;
ITTARAT, I ;
CHANG, CC ;
MCELROY, P ;
MESHNICK, SR .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1994, 67 (02) :183-191
[6]   THE COMPOSITION OF HEMOZOIN FROM PLASMODIUM-FALCIPARUM [J].
ASHONG, JO ;
BLENCH, IP ;
WARHURST, DC .
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 1989, 83 (02) :167-172
[7]   ORIGIN OF REACTIVE OXYGEN SPECIES IN ERYTHROCYTES INFECTED WITH PLASMODIUM-FALCIPARUM [J].
ATAMNA, H ;
GINSBURG, H .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1993, 61 (02) :231-241
[8]   Mode of antimalarial effect of methylene blue and some of its analogues on Plasmodium falciparum in culture and their inhibition of P-vinckei petteri and P-yoelii nigeriensis in vivo [J].
Atamna, H ;
Krugliak, M ;
Shalmiev, G ;
Deharo, E ;
Pescarmona, G ;
Ginsburg, H .
BIOCHEMICAL PHARMACOLOGY, 1996, 51 (05) :693-700
[9]   PLASMODIUM-FALCIPARUM - ISOLATION AND CHARACTERIZATION OF A 55-KDA PROTEASE WITH A CATHEPSIN D-LIKE ACTIVITY FROM PLASMODIUM-FALCIPARUM [J].
BAILLY, E ;
SAVEL, J ;
MAHOUY, G ;
JAUREGUIBERRY, G .
EXPERIMENTAL PARASITOLOGY, 1991, 72 (03) :278-284
[10]  
BALL EG, 1948, J BIOL CHEM, V175, P547