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Trypanosomatids: Role of Farnesyl Pyrophosphate Synthase in Sterol Biosynthetic Pathway

Vaneet Kaur

Abstract


Protozoan infections are the leading cause of morbidity and mortality among parasitic infections of humans. These diseases are predominant in tropical regions of the world and therefore remain an unsolved public health problem. The major death is due to leishmaniasis, and African and American trypanosomiasis caused by species of Trypanosomatidae family. Ergosterol is principal sterol of these trypanosomatids and it is different from cholesterol, the predominant mammalian sterol, by the presence of a 24-methyl group and A7 and AZ2 double bonds. Till date, several agents have been used, but are often regarded with poor efficacy and unsatisfactory safety profiles. This prompted a compelling need of developing of more efficacious and better tolerated medicines. Recently, particular areas of interest are the enzymes of the sterol biosynthesis pathway. It has been found that there are several enzymes in the pathway that have the potential to serve as the targets for anti-trypanosomal chemotherapy. Particularly, Farnesyl diphosphate synthase (FPPS) is proved to be a valid target for tropical diseases chemotherapy. FPPS belongs to the prenyl transferase group, an important regulatory enzyme in isoprenoid biosynthesis pathway. It is one of the key enzymes which are responsible for the production of several precursors for the biosynthesis of isoprenoids like carotenoids, with anolides, ubiquinones, dolichols, and sterols. They are also known to play an important role in farnesylation and geranylation of proteins. Due to their importance, numerous studies have evaluated them as a drug target. Various FPPS inhibitors have find application in treatment of some infectious diseases and also as anti-bacterial or anti-parasitic agents. Analyzing these drugs and their mode of action may provide a new window for investigation and also association of these drugs with other drugs targeting the same pathway at different points may prove a valuable tool for the treatment of these infectious diseases.

Keywords


Trypanosomatidae family, Farnesyl diphosphate synthase, farnesylation and geranylation of proteins

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References


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DOI: https://doi.org/10.37628/ijmb.v1i1.23

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