{"id":{"repo_id":"dundee","oai_identifier":"oai:discovery.dundee.ac.uk:studenttheses/bd2ff371-ca54-4d84-8db8-895b72012b5e"},"canonical_url":"https://search.dev.ndltd.org/etd/dundee/oai:discovery.dundee.ac.uk:studenttheses/bd2ff371-ca54-4d84-8db8-895b72012b5e","repository":{"repo_id":"dundee","name":"University of Dundee","base_url":"https://discovery.dundee.ac.uk/ws/oai"},"display":{"title":"Defining D-Arabinose Metabolism in <i>Leishmania major</i> and <i>Crithidia fasciculata</i>","abstract":"The metabolism of D-Arabinose (D-Ara) in eukaryotes is poorly understood. Arabinose (Ara) is one of the “rare” aldopentose sugars distributed in nature principally as a component of cell wall structures in plants and bacteria. Arabinose exists naturally in both pyranose and furanose conformations and D- and L- configurations. The most abundant form of arabinose is L-arabinose which is present in the arabinogalactans of plants. D-arabinofuranose (D-Araf) is found mainly in the arabinomannans, arabinogalactans, lipoarabinomannans and mycolylarabinogalactan-peptidogalactans of mycobacterial cell walls. However, D-arabinopyranose (D-Arap) is found, uniquely, in cell surface glycoconjugate structures of certain trypanosomatid parasites: Leishmania major lipophosphoglycan (LPG) Crithidia fasciculata lipoarabinogalactan (LAG) and Endotrypanum schaudinni glycoinositol phospholipids (GIPLs). The activated donor molecule of D-Arap has been identified in L. major as GDP-α-D-Arap. However, the source of the GDP-Arap is not fully understood. So far it is known that both L. major and C. fasciculata have a salvage pathway allowing the parasites to internalize D-Ara from the extracellular medium or the lumen of the insect guts and convert it to GDP-α-D-Arap via an arabinose-1-kinase/pyrophosphorylase. A de novo pathway, whereby D-Glucose (D-Glc) is converted to D-Arap via loss of the Glc C-1 carbon atom has been postulated but many details are missing. Many gram-negative bacteria have an Arabinose-5-phosphate isomerase (APIs) enzyme. In bacteria API enzymes catalyse the interconversion of D-ribulose-5-phosphate (Ru5P), the product of the oxidative phase of the pentose phosphate pathway, and D-arabinose-5-phosphate (A5P). A5P is a precursor to 3-deoxy-D-manno-octulosonic acid (KDO) that is a component of the bacterial capsular polysaccharides and lipopolysaccharides (LPS). KDO is an essential component of the cell envelope of gram-negative bacteria. We speculate that trypanosomatids may also convert D-Glc to D-Arap via Ru5P and its isomerisation to A5P followed by dephosphorylation to D-Arap. Apart from cell surface incorporation by L. major and C. fasciculata, it is possible that D-Arap may be used by all the kinetoplastids to make D-erythroascorbate, a C5 ascorbate analogue similar in structure and physicochemical properties to ascorbate (Vitamin C). In animals and plants, L-ascorbate is involved in cellular defence against oxidative stress. The D-erythroascorbate analogue of ascorbate appears in yeast and other fungi, but this antioxidant role is not well understood. The biosynthesis of D-erythroascorbic acid starts from D-Arap, which is oxidized by NAD(P)+ specific dehydrogenases to D-arabino-1,4-lactone, which is further oxidized to D-erythroascorbic acid by D-arabino-1,4-lactone oxidase. The source of the original D-Arap in yeast and fungi is, however, unknown. In summary, central to the problem of eukaryotic D-Arap metabolism is the bioconversion from D-Glc to D-Arap.","abstract_html":"The metabolism of D-Arabinose (D-Ara) in eukaryotes is poorly understood. Arabinose (Ara) is one of the “rare” aldopentose sugars distributed in nature principally as a component of cell wall structures in plants and bacteria. Arabinose exists naturally in both pyranose and furanose conformations and D- and L- configurations. The most abundant form of arabinose is L-arabinose which is present in the arabinogalactans of plants. D-arabinofuranose (D-Araf) is found mainly in the arabinomannans, arabinogalactans, lipoarabinomannans and mycolylarabinogalactan-peptidogalactans of mycobacterial cell walls. However, D-arabinopyranose (D-Arap) is found, uniquely, in cell surface glycoconjugate structures of certain trypanosomatid parasites: Leishmania major lipophosphoglycan (LPG) Crithidia fasciculata lipoarabinogalactan (LAG) and Endotrypanum schaudinni glycoinositol phospholipids (GIPLs). The activated donor molecule of D-Arap has been identified in L. major as GDP-α-D-Arap. However, the source of the GDP-Arap is not fully understood. So far it is known that both L. major and C. fasciculata have a salvage pathway allowing the parasites to internalize D-Ara from the extracellular medium or the lumen of the insect guts and convert it to GDP-α-D-Arap via an arabinose-1-kinase/pyrophosphorylase. A de novo pathway, whereby D-Glucose (D-Glc) is converted to D-Arap via loss of the Glc C-1 carbon atom has been postulated but many details are missing. Many gram-negative bacteria have an Arabinose-5-phosphate isomerase (APIs) enzyme. In bacteria API enzymes catalyse the interconversion of D-ribulose-5-phosphate (Ru5P), the product of the oxidative phase of the pentose phosphate pathway, and D-arabinose-5-phosphate (A5P). A5P is a precursor to 3-deoxy-D-manno-octulosonic acid (KDO) that is a component of the bacterial capsular polysaccharides and lipopolysaccharides (LPS). KDO is an essential component of the cell envelope of gram-negative bacteria. We speculate that trypanosomatids may also convert D-Glc to D-Arap via Ru5P and its isomerisation to A5P followed by dephosphorylation to D-Arap. Apart from cell surface incorporation by L. major and C. fasciculata, it is possible that D-Arap may be used by all the kinetoplastids to make D-erythroascorbate, a C5 ascorbate analogue similar in structure and physicochemical properties to ascorbate (Vitamin C). In animals and plants, L-ascorbate is involved in cellular defence against oxidative stress. The D-erythroascorbate analogue of ascorbate appears in yeast and other fungi, but this antioxidant role is not well understood. The biosynthesis of D-erythroascorbic acid starts from D-Arap, which is oxidized by NAD(P)+ specific dehydrogenases to D-arabino-1,4-lactone, which is further oxidized to D-erythroascorbic acid by D-arabino-1,4-lactone oxidase. The source of the original D-Arap in yeast and fungi is, however, unknown. In summary, central to the problem of eukaryotic D-Arap metabolism is the bioconversion from D-Glc to D-Arap.","abstract_has_math":false,"creators":["Iljazi, Elda"],"institution":"University of Dundee","degree_name":"Doctor of Philosophy","degree_level":"Doctoral Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Ferguson, Michael"],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018","date_published":"2018","updated_at":"2026-07-24T02:08:39Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:discovery.dundee.ac.uk:studenttheses/bd2ff371-ca54-4d84-8db8-895b72012b5e"],"render_values":[{"text":"oai:discovery.dundee.ac.uk:studenttheses/bd2ff371-ca54-4d84-8db8-895b72012b5e","href":null,"code":true}]}]},"links":{"outbound_url":"https://discovery.dundee.ac.uk/en/studentTheses/bd2ff371-ca54-4d84-8db8-895b72012b5e","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Ferguson, Michael"]},{"key":"dc:creator","label":"Author","values":["Iljazi, Elda"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018"]},{"key":"dc:date.issued","label":"Date","values":["2018"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Biological Chemistry and Drug Discovery"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Dundee"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://discovery.dundee.ac.uk/en/studentTheses/bd2ff371-ca54-4d84-8db8-895b72012b5e"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral Thesis"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:discovery.dundee.ac.uk:studenttheses/bd2ff371-ca54-4d84-8db8-895b72012b5e","https://discovery.dundee.ac.uk/en/studentTheses/bd2ff371-ca54-4d84-8db8-895b72012b5e"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://discovery.dundee.ac.uk/files/76931900/Final_PhD_thesis_Elda_Iljazi.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The metabolism of D-Arabinose (D-Ara) in eukaryotes is poorly understood. Arabinose (Ara) is one of the “rare” aldopentose sugars distributed in nature principally as a component of cell wall structures in plants and bacteria. Arabinose exists naturally in both pyranose and furanose conformations and D- and L- configurations. The most abundant form of arabinose is L-arabinose which is present in the arabinogalactans of plants. D-arabinofuranose (D-Araf) is found mainly in the arabinomannans, arabinogalactans, lipoarabinomannans and mycolylarabinogalactan-peptidogalactans of mycobacterial cell walls. However, D-arabinopyranose (D-Arap) is found, uniquely, in cell surface glycoconjugate structures of certain trypanosomatid parasites: Leishmania major lipophosphoglycan (LPG) Crithidia fasciculata lipoarabinogalactan (LAG) and Endotrypanum schaudinni glycoinositol phospholipids (GIPLs). The activated donor molecule of D-Arap has been identified in L. major as GDP-α-D-Arap. However, the source of the GDP-Arap is not fully understood. So far it is known that both L. major and C. fasciculata have a salvage pathway allowing the parasites to internalize D-Ara from the extracellular medium or the lumen of the insect guts and convert it to GDP-α-D-Arap via an arabinose-1-kinase/pyrophosphorylase. A de novo pathway, whereby D-Glucose (D-Glc) is converted to D-Arap via loss of the Glc C-1 carbon atom has been postulated but many details are missing. Many gram-negative bacteria have an Arabinose-5-phosphate isomerase (APIs) enzyme. In bacteria API enzymes catalyse the interconversion of D-ribulose-5-phosphate (Ru5P), the product of the oxidative phase of the pentose phosphate pathway, and D-arabinose-5-phosphate (A5P). A5P is a precursor to 3-deoxy-D-manno-octulosonic acid (KDO) that is a component of the bacterial capsular polysaccharides and lipopolysaccharides (LPS). KDO is an essential component of the cell envelope of gram-negative bacteria. We speculate that trypanosomatids may also convert D-Glc to D-Arap via Ru5P and its isomerisation to A5P followed by dephosphorylation to D-Arap. Apart from cell surface incorporation by L. major and C. fasciculata, it is possible that D-Arap may be used by all the kinetoplastids to make D-erythroascorbate, a C5 ascorbate analogue similar in structure and physicochemical properties to ascorbate (Vitamin C). In animals and plants, L-ascorbate is involved in cellular defence against oxidative stress. The D-erythroascorbate analogue of ascorbate appears in yeast and other fungi, but this antioxidant role is not well understood. The biosynthesis of D-erythroascorbic acid starts from D-Arap, which is oxidized by NAD(P)+ specific dehydrogenases to D-arabino-1,4-lactone, which is further oxidized to D-erythroascorbic acid by D-arabino-1,4-lactone oxidase. The source of the original D-Arap in yeast and fungi is, however, unknown. In summary, central to the problem of eukaryotic D-Arap metabolism is the bioconversion from D-Glc to D-Arap."]},{"key":"dc:title","label":"Title","values":["Defining D-Arabinose Metabolism in <i>Leishmania major</i> and <i>Crithidia fasciculata</i>"]}]}],"canonical_facts":{"dc:contributor.advisor":["Ferguson, Michael"],"dc:creator":["Iljazi, Elda"],"dc:date":["2018"],"dc:date.issued":["2018"],"dc:description.abstract":["The metabolism of D-Arabinose (D-Ara) in eukaryotes is poorly understood. Arabinose (Ara) is one of the “rare” aldopentose sugars distributed in nature principally as a component of cell wall structures in plants and bacteria. Arabinose exists naturally in both pyranose and furanose conformations and D- and L- configurations. The most abundant form of arabinose is L-arabinose which is present in the arabinogalactans of plants. D-arabinofuranose (D-Araf) is found mainly in the arabinomannans, arabinogalactans, lipoarabinomannans and mycolylarabinogalactan-peptidogalactans of mycobacterial cell walls. However, D-arabinopyranose (D-Arap) is found, uniquely, in cell surface glycoconjugate structures of certain trypanosomatid parasites: Leishmania major lipophosphoglycan (LPG) Crithidia fasciculata lipoarabinogalactan (LAG) and Endotrypanum schaudinni glycoinositol phospholipids (GIPLs). The activated donor molecule of D-Arap has been identified in L. major as GDP-α-D-Arap. However, the source of the GDP-Arap is not fully understood. So far it is known that both L. major and C. fasciculata have a salvage pathway allowing the parasites to internalize D-Ara from the extracellular medium or the lumen of the insect guts and convert it to GDP-α-D-Arap via an arabinose-1-kinase/pyrophosphorylase. A de novo pathway, whereby D-Glucose (D-Glc) is converted to D-Arap via loss of the Glc C-1 carbon atom has been postulated but many details are missing. Many gram-negative bacteria have an Arabinose-5-phosphate isomerase (APIs) enzyme. In bacteria API enzymes catalyse the interconversion of D-ribulose-5-phosphate (Ru5P), the product of the oxidative phase of the pentose phosphate pathway, and D-arabinose-5-phosphate (A5P). A5P is a precursor to 3-deoxy-D-manno-octulosonic acid (KDO) that is a component of the bacterial capsular polysaccharides and lipopolysaccharides (LPS). KDO is an essential component of the cell envelope of gram-negative bacteria. We speculate that trypanosomatids may also convert D-Glc to D-Arap via Ru5P and its isomerisation to A5P followed by dephosphorylation to D-Arap. Apart from cell surface incorporation by L. major and C. fasciculata, it is possible that D-Arap may be used by all the kinetoplastids to make D-erythroascorbate, a C5 ascorbate analogue similar in structure and physicochemical properties to ascorbate (Vitamin C). In animals and plants, L-ascorbate is involved in cellular defence against oxidative stress. The D-erythroascorbate analogue of ascorbate appears in yeast and other fungi, but this antioxidant role is not well understood. The biosynthesis of D-erythroascorbic acid starts from D-Arap, which is oxidized by NAD(P)+ specific dehydrogenases to D-arabino-1,4-lactone, which is further oxidized to D-erythroascorbic acid by D-arabino-1,4-lactone oxidase. The source of the original D-Arap in yeast and fungi is, however, unknown. In summary, central to the problem of eukaryotic D-Arap metabolism is the bioconversion from D-Glc to D-Arap."],"dc:identifier":["oai:discovery.dundee.ac.uk:studenttheses/bd2ff371-ca54-4d84-8db8-895b72012b5e","https://discovery.dundee.ac.uk/en/studentTheses/bd2ff371-ca54-4d84-8db8-895b72012b5e"],"dc:identifier.uri":["https://discovery.dundee.ac.uk/files/76931900/Final_PhD_thesis_Elda_Iljazi.pdf"],"dc:language":["eng"],"dc:publisher.department":["Biological Chemistry and Drug Discovery"],"dc:publisher.institution":["University of Dundee"],"dc:relation.isreferencedby":["https://discovery.dundee.ac.uk/en/studentTheses/bd2ff371-ca54-4d84-8db8-895b72012b5e"],"dc:title":["Defining D-Arabinose Metabolism in <i>Leishmania major</i> and <i>Crithidia fasciculata</i>"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral Thesis"],"dc:type.qualificationname":["Doctor of Philosophy"]},"updated_at":"2026-07-24T02:08:39Z"}