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
[131]   A CYTOCHEMICAL ULTRASTRUCTURAL-STUDY OF THE LYSOSOMAL SYSTEM OF DIFFERENT SPECIES OF MALARIA PARASITES [J].
SLOMIANNY, C ;
PRENSIER, G .
JOURNAL OF PROTOZOOLOGY, 1990, 37 (06) :465-470
[132]   INGESTION OF ERYTHROCYTIC STROMA BY PLASMODIUM-CHABAUDI TROPHOZOITES - ULTRASTRUCTURAL-STUDY BY SERIAL SECTIONING AND 3-DIMENSIONAL RECONSTRUCTION [J].
SLOMIANNY, C ;
PRENSIER, G ;
CHARET, P .
PARASITOLOGY, 1985, 90 (JUN) :579-588
[133]   ULTRASTRUCTURAL-LOCALIZATION OF ENZYMES INVOLVED IN THE FEEDING PROCESS IN PLASMODIUM-CHABAUDI AND BABESIA-HYLOMYSCI [J].
SLOMIANNY, C ;
CHARET, P ;
PRENSIER, G .
JOURNAL OF PROTOZOOLOGY, 1983, 30 (02) :376-382
[134]  
SLOMIANNY C, 1982, MOL BIOCH PARASITO S, V5, P695
[135]   On the molecular mechanism of chloroquine's antimalarial action [J].
Sullivan, DJ ;
Gluzman, IY ;
Russell, DG ;
Goldberg, DE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (21) :11865-11870
[136]   Plasmodium hemozoin formation mediated by histidine-rich proteins [J].
Sullivan, DJ ;
Gluzman, IY ;
Goldberg, DE .
SCIENCE, 1996, 271 (5246) :219-222
[137]   EVOLUTION IN THE STRUCTURE AND FUNCTION OF ASPARTIC PROTEASES [J].
TANG, J ;
WONG, RNS .
JOURNAL OF CELLULAR BIOCHEMISTRY, 1987, 33 (01) :53-63
[139]   The heme moiety of malaria pigment (beta-hematin) mediates the inhibition of nitric oxide and tumor necrosis factor-alpha production by lipopolysaccharide-stimulated macrophages [J].
Taramelli, D ;
Basilico, N ;
Pagani, E ;
Grande, R ;
Monti, D ;
Ghione, M ;
Olliaro, P .
EXPERIMENTAL PARASITOLOGY, 1995, 81 (04) :501-511
[140]   USE OF ELECTRON MICROSCOPE AUTORADIOGRAPHY FOR EXAMINING UPTAKE AND DEGRADATION OF HAEMOGLOBIN BY PLASMODIUM-BERGHEI [J].
THEAKSTON, RD ;
FLETCHER, KA ;
MAEGRAITH, BG .
ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY, 1970, 64 (01) :63-+