Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Animals
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Antimalarials / pharmacology
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Aspartic Acid Endopeptidases / biosynthesis
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Aspartic Acid Endopeptidases / genetics
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Aspartic Acid Endopeptidases / metabolism
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Cysteine Endopeptidases / biosynthesis
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Cysteine Endopeptidases / genetics
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Cysteine Endopeptidases / metabolism
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Endopeptidases / metabolism*
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Heme / chemistry
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Heme / metabolism
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Hemoglobins / metabolism*
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Molecular Structure
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Oxidative Stress
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Plasmodium falciparum / enzymology
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Plasmodium falciparum / metabolism*
Substances
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Antimalarials
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Hemoglobins
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Heme
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Endopeptidases
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Cysteine Endopeptidases
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falcipain
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Aspartic Acid Endopeptidases
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plasmepsin