Glycolysis

Glycolysis (glycose+lysis= breaking of glucose) is a sequence of 10 definite reactions which leads to breaking of glucose into pyruvate. This is the first of four steps of aerobic respiration. This cytosolic metabolic pathway produces a net gain of 2 ATPs. This step is also common to anaerobic respiration as it does not require O2. In anaerobic respiration, pyruvate will then be converted to lactate (e.g. skeletal musles) or ethanol and carbon dioxide (e.g. yeast) to re-oxidise electron carrier NADH to provide NAD+ for glycolysis.

 

The apicomplexans Toxoplasma gondii, Plasmodium falciparum and Cryptosporidium species possess all the ten enzymes of glycolysis in the genome. Cryptosporidium species possess one lactate dehydrogenase enzyme (converts pyruvate to lactate) as in P. falciparum , whereas T. gondii possesses 2 lactate dehydrogenase isoforms. Of the enzymes NAD-dependent glycerol-3-phosphate dehydrogenase and FAD-dependent glycerol-3-phophate dehydrogenase (catalyse bidirectional conversion of glycerol-3-phosphate to glycerone phosphate) added to the glycolysis pathway for T. gondii, only the NAD dependent enzyme is present in the Cryptosporidium species. The above mentioned enzymes and other enzymes added in T. gondii glycolysis pathway such as aldehyde reductase, phosphoglucomutase and acylphosphatase are also present in Cryptosporidium muris and added to the pathway here. In addition, gluconeogenesis enzyme, fructose bisphosphatase present in T. gondii is absent in Cryptosporidium and P. falciparum.

 

All the enzymatic activities of the glycolytic pathway except hexokinase were detected in the Cryptosporidium parvum oocysts in the cytosolic fractions. The absence of hexokinase activity being detected is mainly due to the fact that at oocysts stage, amylopectin is degraded to glucose-1-phosphate and the glycolysis starts with phosphoglucomutase activity. In addition, this pathway is characterised by the presence of pyrophosphate dependent phosphofructokinase rather than ATP-dependent enzyme increasing the net yield of ATP to 3 from 2 [1]. The substrate specificities of pyrophosphate specific phosphofructokinase and ADP-specific pyruvate kinase were observed in C. parvum, T. gondii and Eimeria tenella [2]. The recombinant versions of three of these C. parvum enzymes, glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase and lactate dehydrogenase were expressed, purified and crystallised by Senkovich et al [3]. In addition, the structure of triose phosphate isomerase of C. parvum was also elucidated [4].

 

Enzyme EC Number Gene id
Lactate dehydrogenase 1.1.1.27 CMU_006390
Glycerol-3-phosphate dehydrogenase 1.1.1.8 CMU_010130
Glyceraldehyde 3-P dehydrogenase 1.2.1.12 CMU_017050
Hexokinase 2.7.1.1 CMU_017060
Phosphofructokinase 2.7.1.90 CMU_037000
Phosphofructokinase 2.7.1.90 CMU_043050
Pyruvate kinase 2.7.1.40 CMU_028810
Phosphoglycerate kinase 2.7.2.3 CMU_032860
Acylphosphatase 3.6.1.7 CMU_021350
Aldolase 4.1.2.13 CMU_029810
Enolase 4.2.1.11 CMU_039860
Triose phosphate isomerase 5.3.1.1 CMU_029840
Phosphoglucose isomerase 5.3.1.9 CMU_003240
Phosphoglycerate mutase 5.4.2.1 CMU_004090
Phosphoglycerate mutase 5.4.2.1 CMU_014400
Phosphoglycerate mutase 5.4.2.1 CMU_036450
Phosphoglycerate mutase 5.4.2.1 CMU_039200
Phosphoglucomutase 5.4.2.2 CMU_003300
Phosphoglucomutase 5.4.2.2 CMU_003310
Monocarboxylate transporter none CMU_012490
Hexose transporter none CMU_032230
Monocarboxylate transporter none CMU_034520

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
alpha-D-Glucose Host, Starch metabolism alpha-D-Glucose-6P Starch metabolism
    alpha-D-Glucose-1P Starch metabolism, Pyrimidine metabolism
    beta-D-Fructose-6P Aminosugars metabolism, Starch metabolism
    Phosphoenolpyruvate Pyruvate metabolism
    Pyruvate Pyruvate metabolism
    sn-glycerol-3P Phosphatidylethanolamine and phosphatidylserine metabolism
    Lactate Host