Starch and galactose metabolism

The pathway of starch and galactose metabolism is a metabolic capability which is absent in Plasmodium falciparum and present in Coccidia. This pathway is constructed with KEGG reference pathways of starch and sucrose metabolism and galactose metabolism as templates. Both KEGG pathways were combined as only small parts of both reference pathways are present in Toxoplasma gondii and there are few enzymes which are common to both pathways.

 

T. gondii can also store energy in the form of polysaccharides. Unlike Plasmodium, Coccidian species such as Toxoplasma and Eimeria can store carbohydrates in polysaccharide granules. This can be due to the differences in life cycle stages when compared to other apicomplexans. The bradyzoite and sporozoite forms of Coccidians T. gondii and Eimeria tenella store carbohydrates in the form of ‘floridean starch’, a variant of amylopectin which has only been found in red algae previously. It has also been shown that T. gondii and E. tenella prefers UDP-glucose than ADP-glucose as substrate [1, 2]. It has also been shown that the transcription of the Toxoplasma genes encoding the enzymes involved in floridean starch/amylopectin metabolism are stage dependent. The enzymes catalysing catabolic functions such as alpha-glucan phosphorylase, alpha-glucosidase and alpha-amylase are preferentially expressed at the bradyzoite stage and the anabolic enzymes involved in biosynthesis of floridean starch such as starch (amylopectin) synthase and 1,4-alpha-glucan branching enzyme are preferentially expressed in tachyzoites [1]. The gene for bifunctional trehalose phosphate synthase/trehalose phosphatase enzyme was predicted on all Coccidian species and its expression was experimentally confirmed in Cryptosporidium parvum oocysts. It is also suggested as a novel drug target as it is absent in animals [3]. Analysis of the Toxoplasma genome also shows that it can synthesise galactose from UDP-glucose via the action of UDP-glucose 4-epimerase (5.1.3.2) and beta-galactosidase (3.2.1.23).

 

Enzyme EC Number Gene id Protein localisation Localisation data source
Aldehyde reductase 1.1.1.21 TGME49_208040    
Aldehyde reductase 1.1.1.21 TGME49_270100    
Phosphorylase 2.4.1.1 TGME49_310670 Cytosol Previous publication
Starch (amylopectin/floridean starch) synthase 2.4.1.11 TGME49_222800 Nucleus Previous publication
Bifunctional trehalose-6-phosphate synthase/trehalose phosphatase 2.4.1.15; 3.1.3.12 TGME49_297720 Nucleus Previous publication
1,4-alpha-glucan branching enzyme 2.4.1.18 TGME49_209960 Nucleus Previous publication
1,4-alpha-glucan branching enzyme 2.4.1.18 TGME49_246690    
1,4-alpha-glucan branching enzyme 2.4.1.18 TGME49_316520 Cytosol Previous publication
Bifunctional 4-alpha-glucanotransferase/amylo-alpha-1,6-glucosidase 2.4.1.25; 3.2.1.33 TGME49_226910 Cytosol Previous publication
4-alpha-glucanotransferase 2.4.1.25 TGME49_271210    
1,3-beta-glucan synthase 2.4.1.34 TGME49_278110    
Hexokinase 2.7.1.1 TGME49_265450 Cytosol Apiloc; Previous publication
Galactokinase 2.7.1.6 TGME49_229780    
UTP-glucose-1-phosphate uridylyltransferase 2.7.7.9 TGME49_218200    
UTP-glucose-1-phosphate uridylyltransferase 2.7.7.9 TGME49_264780    
alpha-amylase 3.2.1.1 TGME49_283490    
alpha-galactosidase 3.2.1.22 TGME49_309930 Plasma membrane Previous publication
beta-galactosidase 3.2.1.23 TGME49_320588    
Glucan endo-1,3-beta-D-glucosidase 3.2.1.39 TGME49_270850    
UDP-glucose 4-epimerase 5.1.3.2 TGME49_225880 Mitochondrion Previous publication
Glucose-6-phosphate isomerase 5.3.1.9 TGME49_283780 Cytosol Apiloc; Previous publication
Phosphoglucomutase 5.4.2.2 TGME49_285980 Cytosol; Apical Apiloc; Previous publication
Phosphoglucomutase 5.4.2.2 TGME49_318580 Cytosol; Mitochondrion Apiloc; Previous publication

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
alpha-D-Glucose-6P Glycolysis alpha-D-Glucose Glycolysis
alpha-D-Glucose-1P Glycolysis beta-D-Fructose Mannose and fructose metabolism
beta-D-Fructose-6P Glycolysis Trehalose ?
Maltose Host? Dextrin ?