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Polyamine homoeostasis as a drug target in pathogenic protozoa: peculiarities and possibilities
- Source :
- Biochemical Journal
- Publication Year :
- 2011
-
Abstract
- New drugs are urgently needed for the treatment of tropical and subtropical parasitic diseases, such as African sleeping sickness, Chagas' disease, leishmaniasis and malaria. Enzymes in polyamine biosynthesis and thiol metabolism, as well as polyamine transporters, are potential drug targets within these organisms. In the present review, the current knowledge of unique properties of polyamine metabolism in these parasites is outlined. These properties include prozyme regulation of AdoMetDC (S-adenosylmethionine decarboxylase) activity in trypanosomatids, co-expression of ODC (ornithine decarboxylase) and AdoMetDC activities in a single protein in plasmodia, and formation of trypanothione, a unique compound linking polyamine and thiol metabolism in trypanosomatids. Particularly interesting features within polyamine metabolism in these parasites are highlighted for their potential in selective therapeutic strategies.
- Subjects :
- SpdS, spermidine synthase
ornithine decarboxylase (ODC)
AdoMet, S-adenosylmethionine
MGBG, methylglyoxal bis(guanylhydrazone)
Trypanothione
Review Article
Biochemistry
Ornithine decarboxylase
chemistry.chemical_compound
polyamine
S-adenosylmethionine decarboxylase (AdoMetDC)
APA, 1-amino-oxy-3-aminopropane
4MCHA, 4-methylcyclohexylamine
Polyamines
Homeostasis
α-difluoromethylornithine
Leishmania
PAT, putative amino acid transporter
MTA, 5′-methylthioadenosine
LDC, lysine decarboxylase
Ornithine
AdoMetDC, AdoMet decarboxylase
MDL73811, 5′-{[(Z)-4-amino-2-butenyl]methylamino}-5′-deoxyadenosine
Host-Pathogen Interactions
PLP, pyridoxal-5′-phosphate
dcAdoMet, decarboxylated AdoMet
Trypanosoma
DFMO, α-difluoromethylornithine
Antiprotozoal Agents
malaria
OAT, ornithine aminotransferase
Biology
CNS, central nervous system
TryS, trypanothione synthetase
WHO, World Health Organization
AdoDATO, S-adenosyl-1,8-diamino-3-thiooctane
CHA, cyclohexylamine
parasitic diseases
Animals
Humans
SpmS, spermine synthase
Parasites
TryR, trypanothione reductase
Molecular Biology
Cell Biology
Metabolism
biology.organism_classification
DAB, 1,4-diamino-2-butanone
chemistry
ODC, ornithine decarboxylase
biology.protein
TS2, trypanothione disulfide
TSA, TryS-amidase
Spermidine synthase
Polyamine
AdoMao, S-(5′-deoxy-5′-adenosyl)-1-aminoxy-4-(methylsulfonio)-2-cyclopentene
T(SH)2, dihydrotrypanothione
spermidine synthase
Subjects
Details
- ISSN :
- 14708728
- Volume :
- 438
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- The Biochemical journal
- Accession number :
- edsair.doi.dedup.....f619a35d1c764cd1a364a39f735a6cbe