Thesis (M. Phil.)--University of Hong Kong, 2000. / Includes bibliographical references (leaves.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Biochemistry / Master / Master of Philosophy

An enzyme that catalyzed the terminal step in GM(,1) ganglioside biosynthesis was demonstrated in rat brain and rat liver microsomal preparations. This galactosyltransferase enzyme could be solubilized from the Golgi fraction of rat liver homogenates. Anion exchange chromatography resolved two distinct enzymes with activity toward GM(,2) ganglioside. These two activities could be distinguished by such properties as pH optima, detergent requirements, and isoelectric points. The two enzymes had similar molecular weights and cation requirements. / Extensive characterization of the acceptor specificities of galactosyltransferase enzymes present in solubilized Golgi preparations led to the identification of five enzyme reactions. Two activities were identified which had a requirement for acceptors within the glycoprotein family. A single activity supported the biosynthesis of GM(,1) ganglioside only. The fourth galactosyltransferase activity catalyzed the incorporation of galactose into both ganglioside and glycoprotein.

Tay-Sachs and Sandhoff diseases are autosomal recessive disorders of GM2 ganglioside catabolism resulting from deficient activity of lysosomal beta-hexosaminidase A (Hex A) or Hex A and Hex B, respectively. This leads to a massive and fatal accumulation of GM2 ganglioside in the neurons of affected patients. Mouse models of Tay-Sachs and Sandhoff diseases, created via targeted disruption of the Hexa and Hexb genes, revealed that while Hexb -/- mice suffer a profound, fatal neurodegenerative disease as expected, Hexa -/- mice escape disease to about one year. This protection is conferred by an ability to degrade GM2 ganglioside by means of a lysosomal sialidase mediated metabolic bypass. To determine if such a bypass could be made to function in humans, a series of experiments were performed to examine and compare the activity of mouse and human lysosomal sialidases in their ability to promote GM2 catabolism. The results suggest that human lysosomal sialidase, though sluggish, can indeed degrade GM2 when induced sufficiently.

No description available.

Thesis (MSc Natural and Agricultural Sciences (Biochemistry))-University of Pretoria, 2007. / Summary in English and Afrikaans. Includes bibliographical references. Available on the Internet via the World Wide Web.

Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains xvi, 134 p. : ill. (some col.). Advisor: Allan J. Yates, Dept. of Pathology. Includes bibliographical references (p. 118-134).

Thesis (Ph. D.)--University of Hong Kong, 1997. / Includes bibliographical references (leaf 146).

Thesis (M.Med.Sc.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 64-72). Also available in print.