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 parvum and added to the pathway here. In addition, gluconeogenesis enzyme, fructose bisphosphatase present in T. gondii is absent in Cryptosporidium and P. falciparum. The absence of TCA cycle and incomplete electron transport pathway with no ATP synthase complex in C. parvum and Cryptosporidium hominis suggests that glycolysis is the sole energy generation pathway for these organisms and they rely only on anaerobic respiration.

 

All the enzymatic activities of the glycolytic pathway except hexokinase were detected in the C. 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 cgd7_480
Glycerol-3-phosphate dehydrogenase 1.1.1.8 cgd2_210
Glyceraldehyde 3-P dehydrogenase 1.2.1.12 cgd6_3790
Hexokinase 2.7.1.1 cgd6_3800
Phosphofructokinase 2.7.1.90 cgd2_2130
Phosphofructokinase 2.7.1.90 cgd3_1400
Pyruvate kinase 2.7.1.40 cgd1_2040
Phosphoglycerate kinase 2.7.2.3 cgd7_910
Acylphosphatase 3.6.1.7 cgd6_4900
Aldolase 4.1.2.13 cgd1_3020
Enolase 4.2.1.11 cgd5_1960
Triose phosphate isomerase 5.3.1.1 cgd1_3040
Phosphoglucose isomerase 5.3.1.9 cgd2_3200
Phosphoglycerate mutase 5.4.2.1 cgd1_1710
Phosphoglycerate mutase 5.4.2.1 cgd5_2610
Phosphoglycerate mutase 5.4.2.1 cgd7_4270
Phosphoglucomutase 5.4.2.2 cgd2_3260
Phosphoglucomutase 5.4.2.2 cgd2_3270
Hexose transporter none cgd3_4070
Monocarboxylate transporter none cgd4_380
Monocarboxylate transporter none cgd7_2450

 

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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