Steroid biosynthesis

About: Steroid biosynthesis is a research topic. Over the lifetime, 1721 publications have been published within this topic receiving 58977 citations.

Identification of Information Flow-Modulating Drug Targets: A Novel Bridging Paradigm for Drug Discovery

Abstract: Our objective in this study was to identify novel metrics for efficient identification of drug targets using biological network topology data We developed a novel paradigm and metric, namely, bridging centrality, capable of identifying nodes critically involved in connecting or bridging modular subregions of a network The topological and biological characteristics of bridging nodes were delineated in a diverse group of published yeast networks and in three human networks: those involved in cardiac arrest, C21-steroid hormone biosynthesis, and steroid biosynthesis The bridging centrality metric was highly selective for bridging nodes Bridging nodes differed distinctively from nodes with high degree and betweenness centrality Bridging nodes had lower lethality, and their gene expression was consistent with independent regulation Analysis of biological correlates indicated that bridging nodes are promising drug targets from the standpoints of efficacy and side effects The bridging centrality method is a promising computational systems biology tool to aid target identification in drug discovery

Large-Scale Analysis of the Relationship between CYP11A Promoter Variation, Polycystic Ovarian Syndrome, and Serum Testosterone

Abstract: CYP11A, the gene encoding p450scc, a key enzyme in steroid biosynthesis, is a strong biological candidate for polycystic ovary syndrome (PCOS) susceptibility. Four of the five published studies that have examined CYP11A for evidence of linkage and/or association have reported significant relationships with polycystic ovary (PCO) status and/or serum testosterone levels. However, study sizes have been modest, and the current study aimed to reevaluate these findings using significantly larger clinical resources. A pair of CYP11A promoter microsatellites, including the pentanucleotide (D15S520) previously implicated in trait susceptibility, were genotyped in 371 PCOS patients of United Kingdom origin, using both case-control and family-based association methods, and in 1589 women from a population-based birth cohort from Finland characterized for PCO symptomatology and testosterone levels. Although nominally significant differences in allele and genotype frequencies at both loci were observed in the United Kingdom case-control study (for example, an excess of the pentanucleotide four-repeat allele in cases, P = 0.005), these findings were not substantiated in the other analyses, and no discernable relationship was seen between variation at these loci and serum testosterone levels. These studies indicate that the strength of, and indeed the existence of, associations between CYP11A promoter variation and androgen-related phenotypes has been substantially overestimated in previous studies.

Functional expression of human mitochondrial CYP11B2 in fission yeast and identification of a new internal electron transfer protein, etp1

Abstract: Mitochondrial cytochrome P450 enzymes play a crucial role in the steroid biosynthesis in human adrenals, catalyzing regio- and stereospecific hydroxylations. In search of a new model system for the study of these enzymes, we expressed the human CYP11B2 (aldosterone synthase, P450aldo) in fission yeast Schizosaccharomyces pombe. Analysis of the subcellular localization of the P450 enzyme by Western blot analysis, fluorescence microscopy, and electron microscopy demonstrated that the mitochondrial localization signal of the human protein is functional in S. pombe. The transformed yeasts show the inducible ability to convert in vivo considerable amounts of 11-deoxycortisol to cortisol and 11-deoxycorticosterone to corticosterone, 18-hydroxycorticosterone, and aldosterone, respectively. Although in mammalian cells, mitochondrial steroid hydroxylases depend for their activity on an electron transport chain that consists of two proteins, adrenodoxin and adrenodoxin reductase, no coexpression of these proteins i...