Exploiting Unique Structural and Functional Properties of Malarial Glycolytic Enzymes for Antimalarial Drug Development

Table 1

Examples of nonglycolytic functions of glycolytic enzymes in various organisms.

Enzyme	Normal glycolytic function	Moonlighting functions
Hexokinase	Conversion of glucose to glucose 6-phosphate	(i) Transcription regulation [29, 30]; (ii) Apoptosis [31, 33]
Phosphoglucoisomerase	Conversion of glucose 6-phosphate into its isomer fructose 6-phosphate	(i) Cytokine neuroleukin (a nerve growth factor) [19–21]; (ii) Autocrine motility factor [40]; (iii) Differentiation and maturation mediator [41]
Phosphofructokinase	Conversion of fructose 6-phosphate to fructose 1,6-bisphosphate	(i) Vacuolar degradation of peroxisomes (microautophagy) [43]; (ii) Plasminogen binding [44]; (iii) RNA processing [45]
Aldolase	Splitting of fructose-1,6-bisphosphate into two sugar isomers dihydroxyacetone phosphate and glyceraldehyde 3-phosphate	(i) Motility in Toxoplasma gondii [49, 50]; (ii) Cell adhesion in Neisseria meningitidis [51]; (iii) Regulation of WASP/Arp2/3-stimulated actin dynamics [52]
Triosephosphate isomerase	Interconversion of dihydroxyacetone phosphate and glyceraldehyde phosphate	(i) Defense against pathogens via contact-mediated killing by commensal organisms [58]; (ii) Plasminogen binding [44]; (iii) Aggregation causes neurological disorders [59]
Glyceraldehyde-3-phosphate dehydrogenase	Conversion of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate	(i) Plasminogen-binding protein [61]; (ii) Transcription regulation [62]; (iii) Iron metabolism [63]; (iv) Apoptosis [64]
Phosphoglycerate kinase	Conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate	(i) Plasminogen binding [67]; (ii) Actin binding and streptococcal invasion of epithelial cells [68]
Phosphoglycerate mutase	Conversion of 3-phosphoglycerate to 2-phosphoglycerate	Plasminogen binding [44]
Enolase	Conversion of 2-phosphoglycerate to phosphoenol pyruvate	(i) Plasminogen receptor [69]; (ii) Transcription regulation [70, 72]; (iii) DNA methyltransferase DNMT2 inhibitor [71]
Pyruvate kinase	Conversion of phosphoenol pyruvate to pyruvate	(i) Salivary mucin binding [77]; (ii) Transcriptional regulation [82]; (iii) Apoptosis [83]
Lactate dehydrogenase	Conversion of pyruvate to lactate	Epsilon crystalin [85]