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Table 4 Comparison of predicted and experimental reaction lethality.

From: Proteomic and network analysis characterize stage-specific metabolism in Trypanosoma cruzi

Organism and stage

Experimental Method [ref]

Experimental Target

Model reaction(s) constrained

Finding from literature

Full model prediction

Epimastigote model prediction

bloodstream T. brucei***

drug-2-hydroxybenzaldehyde-5-phosphate [37]

fructose-1,6-bisphosphate aldolase

FBAg

lethal

lethal

lethal

T. cruzi amastigotes

drug- 6-phosphogluconate analogues [38]

phosphogluconate dehydrogenase

PGDH

lethal

lethal

lethal

T. cruzi amastigotes

drug- adenosine analogs [39]

glyceraldehyde-3-phosphate dehydrogenase

GAPDg

lethal

lethal

lethal

T. cruzi epimastigotes

drug- bisphosphonates [40]

hexokinase

HEXg, GLUKg

lethal

lethal

lethal

T. cruzi epimastigotes

monoclonal antibody [41]

triosephosphate isomerase

TPIg

lethal

nonlethal

lethal

T. cruzi epimastigotes

drug- peroxynitrite [42]

succinate dehydrogenase and fumarate reductase*

SUCD1rm**, FRDm, FRDgr

lethal

nonlethal

lethal

bloodstream T. brucei

RNAi [43]

phosphofructokinase

PFKg

lethal

lethal

lethal

bloodstream T. brucei

RNAi [43]

phosphoglycerate mutase

PGM

lethal

lethal

lethal

bloodstream T. brucei

RNAi [43]

enolase

ENO

lethal

lethal

lethal

procyclic T. brucei

RNAi [44]

malic enzyme

ME1x, ME1m

lethal

nonlethal

nonlethal

procyclic T. brucei

RNAi [45]

e1 alpha subunit of pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase

PDHam1m, AKGDam1

lethal

nonlethal

lethal

bloodstream T. brucei

RNAi [43]

pyruvate kinase

PYK

lethal

nonlethal

nonlethal

procyclic T. brucei

RNAi [45]

succinyl-CoA synthetase (succinate CoA ligase)

SUCOASm

lethal

nonlethal

nonlethal

L. donovanni promastigotes

nontargeted gene disruption [46]

adenosine kinase

ADK1g

nonlethal

nonlethal

nonlethal

bloodstream T. brucei

RNAi [47]

alanine aminotransferase

ALATA_L, ALATA_Lm

nonlethal

nonlethal

nonlethal

bloodstream T. brucei

RNAi [47]

cytochrome C oxidase subunit IV

CYOO6m

nonlethal

nonlethal

nonlethal

bloodstream T. brucei

RNAi [47]

glycerol-3-phosphate dehydrogenase (FAD)

G3PDcm

nonlethal

nonlethal

nonlethal

procyclic T. brucei

RNAi [45]

e1 subunit of 2-oxoglutarate dehydrogenase

AKGDe1

nonlethal

nonlethal

nonlethal

procyclic T. brucei

RNAi [44]

F1 complex of ATP synthase

ATPSm

nonlethal

nonlethal

nonlethal

procyclic T. brucei

RNAi [48]

glycosomal NADH-dependent fumarate reductase

FRDgr

nonlethal

nonlethal

lethal

procyclic T. brucei

RNAi [44]

mitochondrial fumarate reductase

FRDm

nonlethal

nonlethal

nonlethal

procyclic T. brucei

RNAi [45]

e1 alpha subunit of pyruvate dehydrogenase

PDHam1m

nonlethal

nonlethal

lethal

procyclic T. brucei

RNAi [45]

e1 alpha subunit of pyruvate dehydrogenase, succinate dehydrogenase

PDHam1m, SUCD1rm

nonlethal

nonlethal

lethal

procyclic T. brucei

RNAi [44]

phosphoenolpyruvate carboxykinase

PPCKg

nonlethal

nonlethal

nonlethal

procyclic T. brucei

RNAi [44]

proline oxidase

PRO1xm

nonlethal

nonlethal

nonlethal

procyclic T. brucei

RNAi [45]

succinate dehydrogenase

SUCD1rm

nonlethal

nonlethal

nonlethal

bloodstream T. brucei

targeted gene disruption [49]

aconitase

ACONTm

nonlethal

nonlethal

nonlethal

procyclic T. brucei

targeted gene disruption [50]

acetyl:succinate CoA-transferase

ASCTmr

nonlethal

nonlethal

nonlethal

procyclic T. brucei

targeted gene disruption [51]

pyruvate phosphate dikinase

PPDKg

nonlethal

nonlethal

nonlethal

  1. *Hypothesized to be the main targets of peroxynitrite in T. cruzi
  2. **Succinate dehydrogenase is represented in the model by two reactions, SUCD1rm, and SUCD3-u6m; inhibition of succinate dehydrogenase simulated by inhibiting the first of these two
  3. ***One variation of compound was lethal for T. cruzi, as well
  4. See references [37–51] for details.