The Role of Ingested Hemoglobin in the Nutrition of Schistosoma mansoni

Zussman, R. A.; Bauman, Preston M.; Petruska, J. C.

doi:10.2307/3277456

Cited by 68 publications

(26 citation statements)

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“…[3H]leucine into schistosome proteins (Zussman et al, 1970), as well as the ingestion of red blood cells by male and female worms (Lawrence, 1973), suggested that host haemoglobin was utilized as a substrate for the nutrition of the parasite. Using partially purified material, the schistosome enzyme was shown to be capable of degrading haemoglobin and synthetic peptides containing arginine (Dresden et al, 1981).…”

Section: Introductionmentioning

confidence: 99%

Expression and partial characterization of a cathepsin B-like enzyme (Sm31) and a proposed ‘haemoglobinase’ (Sm32) from Schistosoma mansoni

Götz¹,

Klinkert²

1993

Biochemical Journal

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Schistosoma mansoni protein Sm31 is a cysteine proteinase similar to mammalian lysosomal cathepsin B, proposed to be a key enzyme in schistosome metabolism. Protein Sm32 has been identified as a putative cysteine proteinase termed a ‘haemoglobinase’. Since neither Sm31 nor Sm32 have been completely purified, some controversy of the nature of the ‘true’ digestive enzyme still exists. By incubating a radiolabelled cysteine-proteinase active-site-directed synthetic inhibitor with total S. mansoni proteins, the target of inhibition was Sm31 and not Sm32. The selectivity and irreversibility of inactivation make affinity labelling an invaluable tool for exploring key differences among closely related enzymes and also for studying proteinase activity in a cellular environment. In order to confirm these results, we expressed the complete cDNA sequences of Sm31 and Sm32 in insect cells and analysed the recombinant gene products for proteolytic activities. Cell extracts containing S. mansoni cathepsin B, but not those expressing ‘haemoglobinase’, were demonstrated to cleave a synthetic substrate benzyloxycarbonyl-arginylarginylaminomethylcoumarin in fluorescence assays. Our findings confirm previous assertions that a cysteine proteinase resembling cathepsin B is the haemoglobinase involved in digestion of host proteins. Thus, the original proposal that Sm32 is a cysteine proteinase has not been verified, and its function remains unknown.

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Section: Introductionmentioning

confidence: 99%

Expression and partial characterization of a cathepsin B-like enzyme (Sm31) and a proposed ‘haemoglobinase’ (Sm32) from Schistosoma mansoni

Götz¹,

Klinkert²

1993

Biochemical Journal

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“…Hemoglobin released from the erythrocytes flows into the gut of the schistosome where it is catabolized to dipeptides or free amino acids. These peptides diffuse into, and/or are taken up by, the gastrodermal cells lining the gut and become incorporated into schistosome proteins (8). The spectrum of enzymes that participate in this pathway is not yet fully known, although cysteine endo-and exopeptidases are known to be involved (9 -12).…”

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confidence: 99%

Functional Expression of Dipeptidyl Peptidase I (Cathepsin C) of the Oriental Blood Fluke Schistosoma japonicum in Trichoplusia ni Insect Cells

Hola-Jamriska

King

Dalton

et al. 2000

Protein Expression and Purification

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“…Following the invasion of human skin by aquatic larvae (cercariae), immature parasites (schistosomula) enter the vascular system and in 5-6 weeks mature to adults, which pair and produce eggs. Larval development, adult worm viability, and production of eggs by female worms are all dependent on the acquisition of nutrients from the host bloodstream, including hemoglobin from red blood cells (11) and the abundant serum proteins. Remarkably, no serine proteases have been localized to the gut lumen or gastrodermis of schistosomes, so the proteases involved in digestion are clearly distinct from those key to vertebrate digestion.…”

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confidence: 99%

A Multienzyme Network Functions in Intestinal Protein Digestion by a Platyhelminth Parasite

Delcroix

Sajid

Caffrey

et al. 2006

Journal of Biological Chemistry

212

205

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Proteases frequently function not only as individual enzymes but also in cascades or networks. A notable evolutionary switch occurred in one such protease network that is involved in protein digestion in the intestine. In vertebrates, this is largely the work of trypsin family serine proteases, whereas in invertebrates, cysteine proteases of the papain family and aspartic proteases assume the role. Utilizing a combination of protease class-specific inhibitors and RNA interference, we deconvoluted such a network of major endopeptidases functioning in invertebrate intestinal protein digestion, using the parasitic helminth, Schistosoma mansoni as an experimental model. We show that initial degradation of host blood proteins is ordered, occasionally redundant, and substrate-specific. Although inhibition of parasite cathepsin D had a greater effect on primary cleavage of hemoglobin, inhibition of cathepsin B predominated in albumin degradation. Nevertheless, in both cases, inhibitor combinations were synergistic. An asparaginyl endopeptidase (legumain) also synergized with cathepsin B and L in protein digestion, either by zymogen activation or facilitating substrate cleavage. This protease network operates optimally in acidic pH compartments either in the gut lumen or in vacuoles of the intestinal lining cells. Defining the role of each of these major enzymes now provides a clearer understanding of the function of a complex protease network that is conserved throughout invertebrate evolution. It also provides insights into which of these proteases are logical targets for development of chemotherapy for schistosomiasis, a major global health problem.

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The Role of Ingested Hemoglobin in the Nutrition of Schistosoma mansoni

Cited by 68 publications

References 0 publications

Expression and partial characterization of a cathepsin B-like enzyme (Sm31) and a proposed ‘haemoglobinase’ (Sm32) from Schistosoma mansoni

Expression and partial characterization of a cathepsin B-like enzyme (Sm31) and a proposed ‘haemoglobinase’ (Sm32) from Schistosoma mansoni

Functional Expression of Dipeptidyl Peptidase I (Cathepsin C) of the Oriental Blood Fluke Schistosoma japonicum in Trichoplusia ni Insect Cells

A Multienzyme Network Functions in Intestinal Protein Digestion by a Platyhelminth Parasite

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