Starch and galactose metabolism

The pathway of starch and galactose metabolism is a metabolic capability which is absent in Plasmodium falciparum and present in Coccidians. 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 Coccidia and there are few enzymes which are common to both pathways.

 

Unlike Plasmodium, Coccidian species such as Toxoplasma, Neospora and Eimeria species 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 Toxoplasma gondii, Neospora caninum 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 and Neospora genomes also shows that they 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). The only difference between T. gondii and N. caninum is the absence of gene for alpha-amylase enzyme in the present gene models of N. caninum.

 

Enzyme EC Number Gene id
Aldehyde reductase 1.1.1.21 NCLIV_002950
Aldehyde reductase 1.1.1.21 NCLIV_036520
Phosphorylase 2.4.1.1 NCLIV_054720
Starch synthase 2.4.1.11 NCLIV_005870
Bifunctional trehalose-6-phosphate synthase/trehalose phosphatase 2.4.1.15; 3.1.3.12 NCLIV_006620
1,4-alpha-glucan branching enzyme 2.4.1.18 NCLIV_004200
1,4-alpha-glucan branching enzyme 2.4.1.18 NCLIV_058970
1,4-alpha-glucan branching enzyme 2.4.1.18 NCLIV_058980
1,4-alpha-glucan branching enzyme 2.4.1.18 NCLIV_063470
4-alpha-glucanotransferase 2.4.1.25 NCLIV_035640
Bifunctional 4-alpha-glucanotransferase/amylo-alpha-1,6-glucosidase 2.4.1.25; 3.2.1.33 NCLIV_046100
1,3-beta-glucan synthase 2.4.1.34 NCLIV_067880
Hexokinase 2.7.1.1 NCLIV_039820
Galactokinase 2.7.1.6 NCLIV_030570
UTP-glucose-1-phosphate uridylyltransferase 2.7.7.9 NCLIV_040400
UTP-glucose-1-phosphate uridylyltransferase 2.7.7.9 NCLIV_062050
alpha-amylase 3.2.1.1 Missing in annotation (May be absent)
alpha-galactosidase 3.2.1.22 NCLIV_054050
beta-galactosidase 3.2.1.23 NCLIV_009680
beta-galactosidase 3.2.1.23 NCLIV_009690
glucan endo-1,3-beta-D-glucosidase 3.2.1.39 NCLIV_035930
UDP-glucose 4-epimerase 5.1.3.2 NCLIV_046950
Glucose-6-phosphate isomerase 5.3.1.9 NCLIV_028830
Phosphoglucomutase 5.4.2.2 NCLIV_010960
Phosphoglucomutase 5.4.2.2 NCLIV_014450

 

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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 ?