Date of Award

2011

Degree Type

Dissertation

Department

Biological, Geological and Environmental Sciences

First Advisor

Keulen, Harry van

Subject Headings

Giardia lamblia, Giardiasis, Nitric oxide, Enzymes -- Regulation, Giardia intestinalis, giardiasis, nitric oxide, encystment regulation

Abstract

Giardia intestinalis is a protozoan parasite causing one of the most widely spread water-born intestinal infections: named giardiasis. The parasite has two life forms: trophozoite, responsible for the symptoms, and a transmittable cyst. Cysts are protected from the environment by a cyst wall build up from protein and a complex polysaccharide. The initiation and the key for cyst wall biosynthesis is amination of fructose 6-phosphate by glucosamine 6-phosphate deaminase (GNP). Fructose 6-phosphate is also an intermediate in glycolysis, the main energy producing pathway in trophozoites. The alternative energy source is the arginine dihydrolase pathway (ADHP), which is upregulated upon encystment. The hypothesis tested is that the switch between glycolysis and ADHP is controlled by protein nitrosylation. It was shown that Giardia produces NO and nitrosylates proteins upon encystment. Nitrosylation increased the catalytic activity of GNP and decreased that of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase

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