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1: Biochim Biophys Acta. 2003 Apr 11;1647(1-2):361-6. Links

5-Aminolevulinic acid synthase: mechanism, mutations and medicine.

Shoolingin-Jordan PM, Al-Daihan S, Alexeev D, Baxter RL, Bottomley SS, Kahari ID, Roy I, Sarwar M, Sawyer L, Wang SF.

Biochemistry and Molecular Biology, School of Biological Sciences, The University of Southampton, Southampton, SO16 7PX, UK.

5-Aminolevulinic acid synthase (ALAS), the first enzyme of the heme biosynthesis pathway, catalyses the pyridoxal 5'-phosphate-dependent condensation between glycine and succinyl-CoA to yield 5-aminolevulinic acid (5-amino-4-oxopentanoate). A three-dimensional structural model of Rhodobacter spheroides ALAS has been constructed and used to identify amino acid residues at the active site that are likely to be important for the recognition of glycine, the only amino acid substrate. Several residues have been investigated by site-directed mutagenesis and enzyme variants have been generated that are able to use alanine, serine or threonine. A three-dimensional structure model of 5-aminolevulinic acid synthase from human erythrocytes (ALAS 2) has also been constructed and used to map a range of naturally occurring human mutants that give rise to X-linked sideroblastic anemia. A number of these anemias respond favourably to vitamin B(6) (pyridoxine) therapy, whereas others are either partially responsive or completely refractory. Detailed investigations with selected human mutants have highlighted the importance of arginine-517 that is implicated in glycine carboxyl group binding.

J Egypt Soc Parasitol. 2007 Apr;37(1):39-50. Links

Effect of sublethal concentration of Solanum nigrum on transaminases and lactate dehydrogenase of Biomphalria arabica, in Saudi Arabia.

El-Ansary AK, Al Daihan SK.

Department of Biochemistry, College of Science, King Saud University, P.O Box 22452, Riyadh 11495, Saudi Arabia.

Schistosomes have a complex lifecycle with freshwater intermediate host snails. The snail host represents the weakest point in the lifecycle of parasite. Biomphalaria arabica is intermediate host for Schistosoma mansoni in Saudi Arabia. In this work, aspartate and alanine aminotransferases (AST and ALT) and lactate dehydrogenase (LDH) were measured in the tissue homogenate and haemolymph of B. arabica. Besides, the effect of sublethal concentrations (LC25) of dry powdered Solanum nigrum leaf was tested as plant molluscicide against B. arabica. The studied enzymes were altered in molluscicide-treated snails compared to control. AST and ALT were slightly affected but LDH was the most significantly altered enzyme. The role of the biochemical manipulation in affecting host-parasite relationship was discussed.

Med Sci Monit. 2006 Dec;12(12):RA282-292. Epub 2006 Nov 23. Links

Important aspects of Biomphalaria snail-schistosome interactions as targets for antischistosome drug.

El-Ansary A, Al-Daihan S.

Department of Biochemistry, King Saud University, Riyadh, Saudi Arabia.

The Biomphalaria species are freshwater snails which have a wide distribution and are significant both medically and economically as intermediate hosts for the schistosome parasite, a digenetic trematode causing schistosomiasis, a disease that infects 200 million people, and domestic animals throughout the tropics. The host-parasite relationship is, in principle, a powerful determinant of the biology of infection and disease. Research on snail-schistosome interactions has the potential for making an important contribution to the study of co-evolution or reciprocal adaptation. The association between Biomphalaria and Schistosoma mansoni could well be an excellent model for studies aimed at elucidating some aspects of the compatibility or resistance of this species to schistosomes. Snail hosts and schistosomes appear to have effects on each other's phenotype and genotype. The objective of this review is to clarify the nature of the relationship between schistosome parasites and their freshwater snail hosts. Aspects of snail-schistosome interactions will be traced in relation to behavioral (growth, reproduction, locomotion), immunological, and biochemical changes induced in the host's tissues by the developing intramolluscan stages of the parasite. This may help to identify biochemical or genetic targets for drug design. Manipulation of the intermediate host through these targets could break the cycle of human and snail infection by schistosomes.

1: Med Sci Monit. 2005 Mar;11(3):RA94-103. Links

Stage-specifically expressed schistosome proteins as potential chemotherapeutic targets.

El-Ansary A, Al-Daihan S.

Biochemistry Department, King Saud University, Riyadh, Saudi Arabia.

Digenetic trematodes have evolved behavioral adaptations to their complex life cycles. They have their own strategies to find hosts, locate sites of infection within final and intermediate hosts, escape immune responses, etc. Many of these strategies are highly complex, but they are sometimes quite subtle. While the mechanisms or processes involved in a few parasites are understood, most are not. Schistosoma mansoni parasites inhabit three distinct environments: water, intermediate molluscan hosts, and a definitive vertebrate host. Although targeted chemotherapy and other public health measures are employed to control schistosomiasis and its spread, there is a need for the development of vaccine and new anti-schistosome drugs. Determining how schistosomes interact with different environments may be one mechanism by which suitable vaccine or chemotherapeutic drugs could be developed. Genes expressed in a stage-specific manner may help us to understand the molecular events controlling the complex life cycle of schistosomes. Various proteins are expressed during the life cycle of schistosomes which are essential for its miracidial infection of molluscan hosts, cercarial penetration of vertebrate skin, evasion of the immune responses of both hosts, and other biological activities needed by schistosomes to complete their complex life cycle. Identifying these stage-specific proteins may uncover hidden aspects of parasite biology and provide useful leads for the development of novel intervention strategies.


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