Molecular explorations of the Leishmania donovani 6-phosphogluconolactonase enzyme, a key player in the pentose phosphate pathway

Dhumal, Tushar Tukaram; Kumar, Rajender; Paul, Anindita; Roy, Pradyot Kumar; Garg, Prabha; Singh, Sushma

doi:10.1016/j.biochi.2022.08.006

Cited by 4 publications

(1 citation statement)

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“…Therefore, the upregulated oxidative branch of the PPP probably supplies parasites with ribose-5-phosphate (R5P), which produces RNA and DNA, and NADPH for use as a cellular reductant in cellular metabolism. Recently, PPP has become a very attractive and viable metabolic pathway in drug target research of leishmaniasis, especially some enzymes that are involved in it [ 47 – 50 ], which is expected to lead to the development of novel drugs against VL.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics analysis of visceral leishmaniasis based on urine of golden hamsters

Yuan,

Chen,

Zhao

et al. 2023

Parasites Vectors

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Background Leishmaniasis is one of the most neglected tropical diseases and is spread mainly in impoverished regions of the world. Although many studies have focused on the host’s response to Leishmania invasion, relatively less is known about the complex processes at the metabolic level, especially the metabolic alterations in the infected hosts. Methods In this study, we conducted metabolomics analysis on the urine of golden hamsters in the presence or absence of visceral leishmaniasis (VL) using the ultra-performance liquid chromatography (UPLC) system tandem high-resolution mass spectrometer (HRMS). The metabolic characteristics of urine samples, along with the histopathological change and the parasite burden of liver and spleen tissues, were detected at 4 and 12 weeks post infection (WPI), respectively. Results Amino acid metabolism was extensively affected at both stages of VL progression. Meanwhile, there were also distinct metabolic features at different stages. At 4 WPI, the significantly affected metabolic pathways involved alanine, aspartate and glutamate metabolism, the pentose phosphate pathway (PPP), histidine metabolism, tryptophan metabolism and tyrosine metabolism. At 12 WPI, the markedly enriched metabolic pathways were almost concentrated on amino acid metabolism, including tyrosine metabolism, taurine and hypotaurine metabolism and tryptophan metabolism. The dysregulated metabolites and metabolic pathways at 12 WPI were obviously less than those at 4 WPI. In addition, seven metabolites that were dysregulated at both stages through partial least squares-discriminant analysis (PLS-DA) and receiver-operating characteristic (ROC) tests were screened to be of diagnostic potential. The combination of these metabolites as a potential biomarker panel showed satisfactory performance in distinguishing infection groups from control groups as well as among different stages of infection. Conclusion Our findings could provide valuable information for further understanding of the host response to Leishmania infection from the aspect of the urine metabolome. The proposed urine biomarker panel could help in the development of a novel approach for the diagnosis and prognosis of VL. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%