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. The enzyme acylphosphatase present in Cryptosporidium muris and Cryptosporidium parvum genomes is missing in the gene models of Cryptosporidium hominis. 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 C. hominis 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 C. 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 Chro.70063
Glycerol-3-phosphate dehydrogenase 1.1.1.8 Chro.20028
Glyceraldehyde 3-P dehydrogenase 1.2.1.12 Chro.60434
Hexokinase 2.7.1.1 Chro.60435
Phosphofructokinase 2.7.1.90 Chro.20231
Phosphofructokinase 2.7.1.90 Chro.30172
Pyruvate kinase 2.7.1.40 Chro.10234
Phosphoglycerate kinase 2.7.2.3 Chro.70113
Acylphosphatase 3.6.1.7 Absent
Aldolase 4.1.2.13 Chro.10335
Enolase 4.2.1.11 Chro.50184
Triose phosphate isomerase 5.3.1.1 Chro.10337
Phosphoglucose isomerase 5.3.1.9 Chro.20336
Phosphoglycerate mutase 5.4.2.1 Chro.10196
Phosphoglycerate mutase 5.4.2.1 Chro.50115
Phosphoglycerate mutase 5.4.2.1 Chro.70471
Phosphoglucomutase 5.4.2.2 Chro.20343
Hexose transporter none Chro.30458
Monocarboxylate transporter none Chro.40052
Monocarboxylate transporter none Chro.70281

 

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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