Disease relevance of CYP11A1

• To examine the functional significance of the PR in mitochondrial P450s, we expressed human P450c27 (CYP27) and bovine P450scc (CYP11A1) in an Escherichia coli heterologous expression system, and found that in each one specific proline residue is important for correct folding [1].

High impact information on CYP11A1

• Vasoactive intestinal peptide induces the synthesis of the cholesterol side-chain cleavage enzyme complex in cultured rat ovarian granulosa cells [2].
• It is concluded that VIP regulates the synthesis of the ovarian cholesterol side-chain cleavage enzyme complex, which catalyzes the rate-limiting reaction in progesterone biosynthesis, and that the VIP effect is at least partially mediated through cAMP [2].
• VIP-induced synthesis of the cholesterol side-chain cleavage enzyme complex was accompanied by a dose-related increase in cAMP accumulation and progestin formation [2].
• The origin of steroid hormones in mammals is cholesterol that is metabolized by the mitochondrial CYP11A1 system [3].
• In addition, variation of the ionic strength in these experiments revealed different optimum salt concentrations for the reduction of adrenodoxin reductase and adrenodoxin, respectively, and unraveled dramatically changing reduction rates of CYP11A1 by adrenodoxin [3].

Biological context of CYP11A1

• Under conditions inducing luteal differentiation of theca cells, CYP11A1 and STAR (Steroidogenic acute regulatory protein) were up-regulated by the action of luteinizing hormone (LH), whereas the differentiation-specific up-regulation of INSL3 was suppressed by LH in luteinizing theca cells [4].
• The kinetics of protein-protein interaction and heme reduction between adrenodoxin wild type as well as eight mutants and the cytochromes P450 CYP11A1 and CYP11B1 was studied in detail [5].
• Phosphorylation of bovine adrenodoxin by protein kinase CK2 affects the interaction with its redox partner cytochrome P450scc (CYP11A1) [6].
• Conformational dynamics and molecular interaction reactions of recombinant cytochrome p450scc (CYP11A1) detected by fluorescence energy transfer [7].
• Cysteine mutagenesis and fluorescent labelling of other residues appearing on the distal surface of the CYP11A1 model revealed that V212C and L219C have enhanced fluorescence and a blue shift following association of the mutant CYP11A1 with phospholipid vesicles [8].

Anatomical context of CYP11A1

• Effects of various N-terminal addressing signals on sorting and folding of mammalian CYP11A1 in yeast mitochondria [9].
• The fraction of CYP11A1 that happens to be inserted into the inner mitochondrial membrane is effectively converted into the catalytically active holoenzyme [9].
• The presence together of P-45011 beta and P-450scc in liposomal membranes was found to remarkably stimulate the 11 beta-hydroxylase activity of P-45011 beta and also stimulate the cholesterol desmolase activity of P-450scc [10].
• We have recently established that the antibody against bovine adrenal cytochrome P-450 cholesterol side-chain cleavage enzyme (P-450scc) can be used to specifically detect P-450scc in both bovine placentome and corpus luteum [11].
• Phosphorylation of purified mitochondrial cytochromes P-450 (cholesterol desmolase and 11 beta-hydroxylase) from bovine adrenal cortex [12].

Associations of CYP11A1 with chemical compounds

• Sequence-alignment studies of the bovine mitochondrial cholesterol side-chain cleavage enzyme cytochrome P-450scc with the bacterial cytochrome P-450cam (camphor hydroxylating enzyme) have been undertaken [13].
• The adrenodoxin mutants forming the most stable complexes with CYP11A1 show the fastest rates of reduction and the highest rate constants for cholesterol to pregnenolone conversion [5].
• The results suggest that the C-terminal peptide of adrenodoxin, especially proline 108, affects the structural integrity of the iron-sulfur cluster and that electron donation from adrenodoxin to CYP11A1 and CYP11B1 is determined at least in part by different features of the cytochromes [14].
• Alpha-branched 1,2-diacyl phosphatidylcholines as effectors of activity of cytochrome P450SCC (CYP11A1). Modeling the structure of the fatty acyl chain region of cardiolipin [15].
• There was no difference, however, in the ratios of adrenal CYP11A1 mRNA/3beta-hydroxysteroid dehydrogenase/delta5,delta4-isomerase mRNA and CYP21A1 mRNA/18S ribosomal RNA among the N-POMC-(1-77)-, N-POMC-(1-49)-, and saline-infused groups [16].

Other interactions of CYP11A1

• The rate constants observed differ by a factor of up to 10 among the respective adrenodoxin mutants for CYP11A1 but not for CYP11B1 [5].
• Studies were conducted to determine the importance of de novo cholesterol synthesis and cholesterol side-chain cleavage enzyme in the action of IGF-I in bovine granulosa and thecal cells [17].

Analytical, diagnostic and therapeutic context of CYP11A1

• The interaction of bovine adrenodoxin with CYP11A1 (cytochrome P450scc) and CYP11B1 (cytochrome P45011beta ). Acceleration of reduction and substrate conversion by site-directed mutagenesis of adrenodoxin [5].

References