Polyamine metabolism in Leishmania: from arginine to trypanothione

被引:0
作者
Gianni Colotti
Andrea Ilari
机构
[1] University “Sapienza”,Institute of Biology and Molecular Pathology, CNR, c/o Department of Biochemical Sciences
来源
Amino Acids | 2011年 / 40卷
关键词
Polyamines; Arginine; Trypanothione; Redox metabolism; Drug targets;
D O I
暂无
中图分类号
学科分类号
摘要
Polyamines (PAs) are essential metabolites in eukaryotes, participating in a variety of proliferative processes, and in trypanosomatid protozoa play an additional role in the synthesis of the critical thiol trypanothione. The PAs are synthesized by a metabolic process which involves arginase (ARG), which catalyzes the enzymatic hydrolysis of l-arginine (l-Arg) to l-ornithine and urea, and ornithine decarboxylase (ODC), which catalyzes the enzymatic decarboxylation of l-ornithine in putrescine. The S-adenosylmethionine decarboxylase (AdoMetDC) catalyzes the irreversible decarboxylation of S-adenosylmethionine (AdoMet), generating the decarboxylated S-adenosylmethionine (dAdoMet), which is a substrate, together with putrescine, for spermidine synthase (SpdS). Leishmania parasites and all the other members of the trypanosomatid family depend on spermidine for growth and survival. They can synthesize PAs and polyamine precursors, and also scavenge them from the microenvironment, using specific transporters. In addition, Trypanosomatids have a unique thiol-based metabolism, in which trypanothione (N1-N8-bis(glutathionyl)spermidine, T(SH)2) and trypanothione reductase (TR) replace many of the antioxidant and metabolic functions of the glutathione/glutathione reductase (GR) and thioredoxin/thioredoxin reductase (TrxR) systems present in the host. Trypanothione synthetase (TryS) and TR are necessary for the protozoa survival. Consequently, enzymes involved in spermidine synthesis and its utilization, i.e. ARG, ODC, AdoMetDC, SpdS and, in particular, TryS and TR, are promising targets for drug development.
引用
收藏
页码:269 / 285
页数:16
相关论文
共 50 条
[1]   Polyamine metabolism in Leishmania: from arginine to trypanothione [J].
Colotti, Gianni ;
Ilari, Andrea .
AMINO ACIDS, 2011, 40 (02) :269-285
[2]   The parasite-specific trypanothione metabolism of trypanosoma and leishmania [J].
Krauth-Siegel, RL ;
Meiering, SK ;
Schmidt, H .
BIOLOGICAL CHEMISTRY, 2003, 384 (04) :539-549
[3]   Polyamine Metabolism in Leishmania Parasites: A Promising Therapeutic Target [J].
Carter, Nicola S. ;
Kawasaki, Yumena ;
Nahata, Surbhi S. ;
Elikaee, Samira ;
Rajab, Sara ;
Salam, Leena ;
Alabdulal, Mohammed Y. ;
Broessel, Kelli K. ;
Foroghi, Forogh ;
Abbas, Alyaa ;
Poormohamadian, Reyhaneh ;
Roberts, Sigrid C. .
MEDICAL SCIENCES, 2022, 10 (02)
[4]   Capillary electrophoresis reveals polyamine metabolism modulation in Leishmania (Leishmania) amazonensis wild-type and arginase-knockout mutants under arginine starvation [J].
Castilho-Martins, Emerson A. ;
Canuto, Gisele A. B. ;
Muxel, Sandra Marcia ;
Laranjeira da Silva, Maria Fernanda ;
Floeter-Winter, Lucile Maria ;
del Aguila, Carmen ;
Lopez-Gonzalvez, Angeles ;
Barbas, Coral .
ELECTROPHORESIS, 2015, 36 (18) :2314-2323
[5]   Targeting Trypanothione Metabolism in Trypanosomatids [J].
Gonzalez-Montero, Maria-Cristina ;
Andres-Rodriguez, Julia ;
Garcia-Fernandez, Nerea ;
Perez-Pertejo, Yolanda ;
Reguera, Rosa M. ;
Balana-Fouce, Rafael ;
Garcia-Estrada, Carlos .
MOLECULES, 2024, 29 (10)
[6]   Trypanothione Metabolism as Drug Target for Trypanosomatids [J].
Pineyro, Maria Dolores ;
Arias, Diego ;
Parodi-Talice, Adriana ;
Guerrero, Sergio ;
Robello, Carlos .
CURRENT PHARMACEUTICAL DESIGN, 2021, 27 (15) :1834-1846
[7]   Mapping the functional synthetase domain of trypanothione synthetase from Leishmania major [J].
Oza, Sandra L. ;
Wyllie, Susan ;
Fairlamb, Alan H. .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 2006, 149 (01) :117-120
[8]   Trypanothione overproduction and resistance to antimonials and arsenicals in Leishmania [J].
Mukhopadhyay, R ;
Dey, S ;
Xu, NX ;
Gage, D ;
Lightbody, J ;
Ouellette, M ;
Rosen, BP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (19) :10383-10387
[9]   Targeting Polyamine Metabolism for Finding New Drugs Against Leishmaniasis: A Review [J].
Ilari, Andrea ;
Fiorillo, Annarita ;
Baiocco, Paola ;
Poser, Elena ;
Angiulli, Gabriella ;
Colotti, Gianni .
MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2015, 15 (03) :243-252
[10]   Dietary arginine affects energy metabolism through polyamine turnover in juvenile Atlantic salmon (Salmo salar) [J].
Andersen, Synne M. ;
Holen, Elisabeth ;
Aksnes, Anders ;
Ronnestad, Ivar ;
Zerrahn, Jens-Erik ;
Espe, Marit .
BRITISH JOURNAL OF NUTRITION, 2013, 110 (11) :1968-1977