Incorporation of 14C-amino acids by malaria (Plasmodium lophurae). I. Role of ions and amino acids in the medium

Iw, Sherman; Ja, Ruble; Tanigoshi, Linda

doi:10.1093/milmed/134.9.954

Cited by 27 publications

(19 citation statements)

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“…37 The amino acids derived from hemoglobin degradation are incorporated into parasite proteins or utilized for energy metabolism. 38,39 It has also been suggested that removal of hemoglobin through degradation provides space in the red blood cell for the growing parasite and prevents premature erythrocyte lysis. 40 Massive degradation of hemoglobin generates a large amount of toxic heme, which causes membrane damage due to its peroxidative properties.…”

Section: Hemoglobin Degradation Pathwaymentioning

confidence: 99%

Falcipain‐2 inhibitors

Ettari

Bova

Zappalà

et al. 2009

Medicinal Research Reviews

132

106

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Malaria, particularly that one caused by Plasmodium falciparum, remains a serious health problem in Africa, South America, and many parts of Asia where it afflicts about 500 million people and is responsible for the death of more than one million children each year. The main reasons for the persistence of malaria are the emergence of resistance to common antimalarial drugs, inadequate control of mosquito vectors, and the lack of effective vaccines. Therefore, the identification and characterization of new targets for antimalarial chemotherapy are of urgent priority. This review is focused on inhibitors of falcipain-2, a cysteine protease from P. falciparum, which represents one of the most promising targets for antimalarial drug design. Falcipain-2 is a key enzyme in the life cycle of P. falciparum since it degrades hemoglobin, at the early trophozoite stage, and cleaves ankyrin and protein 4.1, the cytoskeletal elements vital to the stability of red cell membrane, at the schizont stage. The main classes of falcipain-2 inhibitors are peptides or peptidomimetics bearing the most popular pharmacophores of cysteine protease inhibitors, such as vinyl sulfones, halomethyl ketones, and aldehydes. Furthermore, many other chemotypes have been identified as inhibitors of falcipain-2, such as isoquinolines, thiosemicarbazones, and chalcones. These inhibitors represent all classes, which, to the best of our knowledge, have been disclosed in journal articles to date.

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Section: Hemoglobin Degradation Pathwaymentioning

confidence: 99%

Falcipain‐2 inhibitors

Ettari

Bova

Zappalà

et al. 2009

Medicinal Research Reviews

132

106

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“…The results of the present study clearly demonstrate that enhanced activity of adenylate eyclase in the presence of chloroquine was responsible for the increased production of cyclic AMP. Sherman and Tanigoshi (1972) have shown that incubation of erythrocytes with chloroquine significantly depressed the level of ATP inside erythrocytes. The observed elevation in the activities of adenylate eyclase, Na+K"'-ATPase and Ca+-Mg+--ATPase in the membrane preparations of parasitized erythrocytes in the presence of chloroquine may indicate active utilization of ATP, thus providing an explanation for the decreased concentration of ATP in the presence of chloroquine.…”

Section: In Vitro Effect Of Chloroquine On the Activities Of Membranementioning

confidence: 99%

ERYTHROCYTE MEMBRANE‐BOUND ENZYMES IN MASTOMYS NATALENSIS DURING PLASMODIUM BERGHEI INFECTION

Khare

Saxena

Sen

et al. 1984

Aust J Exp Biol Med

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Summary The pattern of activity of certain membrane‐associated enzymes was followed in the erythrocytes of Plasmodium berghei‐infected Mastomys natalensis. Parasitized erythrocytes were separated from non‐parasitized populations by percoll‐density gradient centrifugation. The activity of adenylate cyclase was markedly increased while those of ATPase, acid phosphatase, β‐glucuronidase and N‐acetyl‐β‐D‐glucosaminidase were considerably decreased in the membrane preparations of parasitized erythrocytes as compared to normal erythrocytes. There was a decrease in the activity of ATPase and an increase of adenylate cyclase in the membrane preparations of non‐parasitized erythrocytes. However, other enzymes did not alter to a significant extent in non‐parasitized erythrocytes. Chloroquine (in vitro) stimulated adenylate cyclase, Na+ K+‐ATPase and Ca++Mg++‐ATPase while acetylcholinesterase was significantly inhibited.

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“…During the blood stages, the malaria parasite utilizes host Hb as a major source of amino acids for its own protein synthesis [3,4]. However, the degradation of Hb in the food vacuole is accompanied by the release of free haem, which is extremely toxic to the parasite [5].…”

Section: Introductionmentioning

confidence: 99%

Reaction of artemisinin with haemoglobin: implications for antimalarial activity

Kannan

Kumar

Sahal

et al. 2005

Biochemical Journal

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Elucidation of the principal targets of the action of the antimalarial drug artemisinin is an ongoing pursuit that is important for understanding the action of this drug and for the development of more potent analogues. We have examined the chemical reaction of Hb with artemisinin. The protein-bound haem in Hb has been found to react with artemisinin much faster than is the case with free haem. It appears that the uptake of Hb and the accumulation of artemisinin into the food vacuole, together with the preferred reactivity of artemisinin with haem in Hb, may make Hb the primary target of artemisinin's antimalarial action. Both monoalkylated (HA) and dialkylated (HAA) haem derivatives of artemisinin have been isolated. These 'haemarts' bind to PfHRP II (Plasmodium falciparum histidine-rich protein II), inhibiting haemozoin formation, and possess a significantly decreased ability to oxidize ascorbic acid. The accelerated formation of HAA from Hb is expected to decrease the ratio of haem to its alkylated derivatives. The haemarts that are generated from 'haemartoglobins' may bring about the death of malaria parasite by a two-pronged effect of stalling the formation of haemozoin by the competitive inhibition of haem binding to its templates and creating a more reducing environment that is not conducive to the formation of haemozoin.

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Incorporation of 14C-amino acids by malaria (Plasmodium lophurae). I. Role of ions and amino acids in the medium

Cited by 27 publications

References 0 publications

Falcipain‐2 inhibitors

Falcipain‐2 inhibitors

ERYTHROCYTE MEMBRANE‐BOUND ENZYMES IN MASTOMYS NATALENSIS DURING PLASMODIUM BERGHEI INFECTION

Reaction of artemisinin with haemoglobin: implications for antimalarial activity

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