Review Article

Glycolysis in the African Trypanosome: Targeting Enzymes and Their Subcellular Compartments for Therapeutic Development

Table 1

The T. brucei glycolytic enzymes as potential drug targets.

EnzymeaPTS type% identity to human counterpartStatus of therapeutic developmentb

TbHK1 PTS2 [24]38% to HKDC1CV [7, 9], GV [7, 9],
36% to HXK3
TbHK2PTS2 [24]GV [6, 7]
PGIPTS1 [25]57% to PGI isoform 2
PFKPTS1 [25]27 % to PFK, platelet isoformCV [26], GV [6]
ALDPTS2 [26]49% to brain (C isozyme)CV [27], GV [28]
TPII-PTS [29]54% to isoform 1GV [30]
GPDHPTS1 [25, 31]38% to GPDH2
GAPDHPTS1 [25]55% to spermatogenic GAPDH-2CV [32], GV [28]
PGK
 PGKAI-PTS [33]42% to PGK 1
 PGKBN/A43% to PGK 1
 PGKCPTS1 [25, 34]44% to PGK 1GV [35], CV [36]
PGMN/A24% to CAMTA1GV [6]
ENON/A63% to ENO2GV [6]
PKN/A50% to PKLR

aFor enzyme abbreviations, see Figure 1. CAMTA1: calmodulin binding transcription activator 1; HKDC1: hexokinase domain containing protein 1; HXK3: hexokinase type 3; N/A: not applicable because the protein is cytosolic; PKLR: pyruvate kinase, liver, and RBC.
bStatus: CV: chemically validated target—inhibitors against the target are toxic to parasites; GV: genetically validated target—genetic manipulation of the enzyme leads to growth defects or cell death.