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 cyst forming Coccidians Toxoplasma gondii and Neospora caninum possess all the ten enzymes of glycolysis in the genome. They also possess 2 lactate dehydrogenase isoforms (converts pyruvate to lactate). There are a number of experimental studies carried out with T. gondii lactate dehydrogenases which has enabled better understanding of their localisation, structure and function (T. gondii glycolysis pathway). The absence of two subunits of ATP synthase and the presence of lactate dehydrogenase in P. falciparum suggests that it relies mainly on glycolysis for ATP generation. It has also been demonstrated in intra-erythrocytic stage of P. falciparum that all the glucose consumed are converted to fermentation products [1]. Although electron transport chain is functional and essential for ATP production at least in T. gondii tachyzoite [2], it is not exactly known of the role of different metabolic pathways in ATP generation in T. gondii and N. caninum. The glycolysis and anaerobic fermentation may also be the main source of ATP in other life cycle stages.

 

The enzymes NAD-dependent glycerol-3-phosphate dehydrogenase and FAD-dependent glycerol-3-phophate dehydrogenase which catalyse bidirectional conversion of glycerol-3-phosphate to glycerone phosphate were added to glycolysis pathway in MPMP. This is because the reaction catalysed by these  enzymes will lead to increased glycolytic intermediate glycerone phosphate, which will increase pyruvate and ATP production via the actions of triose phosphate isomerise and enzymes downstream of it. The above mentioned enzymes and other enzymes added in MPMP glycolysis pathway such as aldehyde reductase and phosphoglucomutase are also present in N. caninum genome as in T. gondii and added to the pathway here. The acylphosphate enzyme present in P. falciparum and T. gondii is missing in N. caninum gene models. In addition, gluconeogenesis enzyme, fructose bisphosphatase (absent in P. falciparum) is present in T. gondii and N. caninum and added to the glycolysis pathway. The enzyme glycerol kinase, present in P. falciparum glycolysis pathway is absent in Toxoplasma and Neospora genomes. There are 4 copies of phosphofructokinase in T. gondii, whereas only three copies are present in N. caninum genome. There is also difference in the copy number of monocarboxylate transporter with Toxoplasma and Neospora possessing two and one copies respectively.

 

Enzyme EC Number Gene id
Aldehyde reductase 1.1.1.21 NCLIV_002950
Lactate dehydrogenase (LDH1) 1.1.1.27 NCLIV_032330
Lactate dehydrogenase (LDH2) 1.1.1.27 NCLIV_042910
Glycerol-3-phosphate dehydrogenase 1.1.1.8 NCLIV_001180
Glycerol-3-phosphate dehydrogenase 1.1.1.8 NCLIV_043550
Glycerol-3-phosphate dehydrogenase 1.1.5.3 NCLIV_024220
Glyceraldehyde 3-P dehydrogenase 1.2.1.12 NCLIV_037190
Glyceraldehyde 3-P dehydrogenase 1.2.1.12 NCLIV_041940
Hexokinase 2.7.1.1 NCLIV_039820
Phosphofructokinase 2.7.1.90 NCLIV_017040
Phosphofructokinase 2.7.1.90 NCLIV_023360
Phosphofructokinase 2.7.1.90 NCLIV_046050
Pyruvate kinase 2.7.1.40 NCLIV_015200
Phosphoglycerate kinase 2.7.2.3 NCLIV_005420
Phosphoglycerate kinase 2.7.2.3 NCLIV_011270
Fructose bisphosphatase 3.1.3.11 NCLIV_020310
Fructose bisphosphatase 3.1.3.11 NCLIV_065240
Acylphosphatase 3.6.1.7 NCLIV_0275 (Gene model incorrect)
Aldolase 4.1.2.13 NCLIV_050370
Aldolase 4.1.2.13 NCLIV_050380
Enolase (ENO1) 4.2.1.11 NCLIV_037490
Enolase (ENO2) 4.2.1.11 NCLIV_037500
Triose phosphate isomerase 5.3.1.1 NCLIV_046900
Phosphoglucose isomerase 5.3.1.9 NCLIV_028830
Phosphoglycerate mutase 5.4.2.1 NCLIV_005940
Phosphoglycerate mutase 5.4.2.1 NCLIV_006170
Phosphoglycerate mutase 5.4.2.1 NCLIV_011300
Phosphoglycerate mutase 5.4.2.1 NCLIV_034520
Phosphoglucomutase 5.4.2.2 NCLIV_010960
Phosphoglucomutase 5.4.2.2 NCLIV_014450
Monocarboxylate transporter none NCLIV_006330
Facilitative glucose transporter (Hexose transporter) none NCLIV_051560

 

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Sources and fates of metabolites

 

Substrate Source pathways Product Fate pathways
alpha-D-Glucose Host, Starch and galactose metabolism alpha-D-Glucose-6P Pentose phosphate cycle, Starch and galactose metabolism
    alpha-D-Glucose-1P Starch and galactose metabolism, Pyrimidine metabolism
beta-D-Fructose-6P Pentose phosphate cycle beta-D-Fructose-6P Pentose phosphate cycle, Aminosugars metabolism, Starch and galactose metabolism
Glyceraldehyde-3P Pentose phosphate cycle Glyceraldehyde-3P Pentose phosphate cycle, Pyridoxal phosphate (vitamin B6) metabolism
    Phosphoenolpyruvate Pyruvate metabolism, Shikimate metabolism
    Pyruvate Pyruvate metabolism, Alanine metabolism
    sn-glycerol-3P Phosphatidylethanolamine and phosphatidylserine metabolism
    Glycerone-P Fatty acid synthesis in the apicoplast
    Lactate Host