The isoprene biosynthetic pathway provides the cell with cholesterol, ubiquinone, dolichol, and other nonsterol
metabolites. Farnesylpyrophosphate synthetase (EC 2.5.1.10 ) catalyzes the formation of both geranyl and
farnesylpyrophosphate from isopentenylpyrophosphate and dimethylallyl pyrophosphate.
NCBI Summary:
The isoprene biosynthetic pathway provides the cell with cholesterol, ubiquinone, dolichol, and other nonsterol metabolites. Farnesylpyrophosphate synthetase (EC 2.5.1.10) catalyzes the formation of both geranyl and farnesylpyrophosphate from isopentenylpyrophosphate and dimethylallyl pyrophosphate.[supplied by OMIM]
General function
Enzyme
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Cellular localization
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Ovarian function
Steroid metabolism
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Owens GE, et al reported ovulatory surges of human CG prevent hormone-induced granulosa cell tumor formation leading to the identification of
tumor-associated changes in the transcriptomes.
The authors used a
transgenic mouse model in which granulosa cell tumors occur with 100%
penetrance in CF-1 mice that harbor a novel transgene encoding a chimeric
LHbeta subunit. When this transgene is expressed in other strains of mice,
including (C57BL/6female x CF-1male,Tg) F-1 hybrids, luteomas develop even
though levels of LH remain high. This dichotomous response permits a
longitudinal comparison of global changes in transcriptomes uniquely
associated with either granulosa cell tumors or luteomas. The authors report
numerous changes in the transcriptome, including a decrease in LH receptor
mRNA and increases in several mRNAs that encode secreted proteins previously
associated with granulosa cell tumors. They identified a
constellation of mRNAs that encode proteins that may serve as new markers for
this tumor phenotype. Additional experiments indicated that periodic treatment
with human CG prevented formation of granulosa cell tumors in mice genetically
predisposed to tumor development and, instead, led to the appearance of
luteomas. More importantly, ovarian transcriptomes from the luteomas induced
by ovulatory doses of human CG permitted refined confirmation of gene
expression changes that were uniquely associated with either granulosa cell
tumors in the permissive CF-1 genetic background or in luteomas in the F-1
hybrids. Together, these dynamic changes in the ovarian transcriptome indict
various signaling pathways potentially involved in mediating the actions of LH
over time and, depending on genetic background, the formation of either a
luteoma or a granulosa cell tumor. FARNESYL DIPHOSPHATE SYNTHASE
is a gene that is down regulated in granulosa cell tumors.
Expression regulated by
Growth Factors/ cytokines
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Ovarian localization
Cumulus
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Oocyte regulation of metabolic cooperativity between mouse cumulus cells and oocytes: BMP15 and GDF9 control cholesterol biosynthesis in cumulus cells. Su YQ et al. Oocyte-derived bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are key regulators of follicular development. Here we show that these factors control cumulus cell metabolism, particularly glycolysis and cholesterol biosynthesis before the preovulatory surge of luteinizing hormone. Transcripts encoding enzymes for cholesterol biosynthesis were downregulated in both Bmp15(-/-) and Bmp15(-/-) Gdf9(+/-) double mutant cumulus cells, and in wild-type cumulus cells after removal of oocytes from cumulus-cell-oocyte complexes. Similarly, cholesterol synthesized de novo was reduced in these cumulus cells. This indicates that oocytes regulate cumulus cell cholesterol biosynthesis by promoting the expression of relevant transcripts. Furthermore, in wild-type mice, Mvk, Pmvk, Fdps, Sqle, Cyp51, Sc4mol and Ebp, which encode enzymes required for cholesterol synthesis, were highly expressed in cumulus cells compared with oocytes; and oocytes, in the absence of the surrounding cumulus cells, synthesized barely detectable levels of cholesterol. Furthermore, coincident with reduced cholesterol synthesis in double mutant cumulus cells, lower levels were also detected in cumulus-cell-enclosed double mutant oocytes compared with wild-type oocytes. Levels of cholesterol synthesis in double mutant cumulus cells and oocytes were partially restored by co-culturing with wild-type oocytes. Together, these results indicate that mouse oocytes are deficient in synthesizing cholesterol and require cumulus cells to provide products of the cholesterol biosynthetic pathway. Therefore, oocyte-derived paracrine factors, particularly, BMP15 and GDF9, promote cholesterol biosynthesis in cumulus cells, probably as compensation for oocyte deficiencies in cholesterol production.