Many facets of mammalian lanosterol 14alpha-demethylase from the evolutionarily conserved cytochrome P450 family CYP51.
Lanosterol 14alpha-demethylase is a cytochrome P450 enzyme of the cholesterol biosynthetic pathway belonging to the CYP51 gene family which is the most evolutionarily conserved member of the CYP superfamily. Mammalian (human, mouse, rat, pig) CYP51 genes are unique in sharing several common characteristics: highly conserved exon/intron borders and proximal promoter structures, ubiquitous expression at the highest level in the testis, and appearance of testis-specific transcripts that arise from differential polyadenylation site usage. CYP51 protein demethylates lanosterol to form follicular fluid meiosis-activating sterol, FF-MAS, which is, besides being an intermediate of cholesterol biosynthesis, also a signaling sterol that accumulates in ovaries. CYP51 protein resides in the endoplasmatic reticulum of most cells and also in acrosomal membranes of spermatids where transport through the Golgi apparatus is suggested. While sterol regulatory element binding protein (SREBP)-dependent transcriptional regulation of CYP51 contributes to synthesis of cholesterol, the germ-cell-specific cAMP/CREMtau-dependent upregulation might contribute to increased production of MAS.
Debeljak
Natasa
N
Medical Center for Molecular Biology, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, Slovenia.
Fink
Martina
M
Rozman
Damjana
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008540:Meiosis; D051379:Mice; D008954:Models, Biological; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D011544:Pseudogenes; D051381:Rats; D017386:Sequence Homology, Amino Acid; D058886:Sterol 14-Demethylase; D051780:Sterol Regulatory Element Binding Protein 1; D013552:Swine; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D022762:CCAAT-Enhancer-Binding Proteins; C548418:CYP51A1 protein, human; C548417:Cyp51 protein, rat; D004268:DNA-Binding Proteins; C497387:SREBF1 protein, human; C497388:Srebf1 protein, mouse; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C548415:Cyp51 protein, mouse; D058886:Sterol 14-Demethylase