The role of cytochrome b5 in adrenal microsomal steroidogenesis

Kominami, Shiro; Ogawa, Norio; Morimune, R; De-Ying, Huang; Takemori, Shigeki

doi:10.1016/0960-0760(92)90011-7

Cited by 88 publications

(34 citation statements)

References 29 publications

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“…Cytochrome b 5 also enhances the 17,20 lyase activity of human P450c17 (24,(55)(56)(57) by allosteric action that does not involve electron donation (13). Whereas P450c17 is expressed in both the human zona fasciculata and zona reticularis and shows little change as a function of age, the expression of cytochrome b 5 increases in the adrenal zona reticularis at the onset of adrenarche (58, 59) lyase activity independently and that each mechanism is sufficient to achieve nearly maximal induction on its own.…”

Section: Discussionmentioning

confidence: 99%

Regulation of 17,20 Lyase Activity by Cytochrome b5 and by Serine Phosphorylation of P450c17

Pandey

Miller

2005

Journal of Biological Chemistry

149

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Section: Discussionmentioning

confidence: 99%

Regulation of 17,20 Lyase Activity by Cytochrome b5 and by Serine Phosphorylation of P450c17

Pandey

Miller

2005

Journal of Biological Chemistry

149

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“…Selective stimulation of CYP17 cleavage activity was first demonstrated in 1982 by Katagiri et al (1982) who found that the extent of side-chain cleavage was dependent on the concentration of cytochrome b 5 . The hydroxylase and lyase activities of isolated adrenal and testicular microsomes were suppressed in the presence of cytochrome b 5 antibodies (Ishii-Ohba et al 1984, Kominami et al 1992. Further evidence for cytochrome b 5 involvement arrived from histological studies of adenomal tissues retrieved from Cushing's syndrome patients who had impaired production of androgens.…”

Section: Cytochrome B 5 Modulates Cyp17 Activitymentioning

confidence: 96%

Cytochrome b5 modulation of 17α hydroxylase and 17–20 lyase (CYP17) activities in steroidogenesis

Akhtar¹,

Kelly²,

Kaderbhai³

2005

Journal of Endocrinology

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CYP17 is a steroidogenic enzyme located in the zona fasciculata and zona reticularis of the adrenal cortex and gonad tissues and which has dual functions -hydroxylation and as a lyase. The first activity gives hydroxylation of pregnenolone and progesterone at the C 17 position to generate 17 -hydroxypregnenolone and 17 -hydroxyprogesterone, while the second enzymic activity cleaves the C 17 -C 20 bond of 17 -hydroxypregnenolone and 17 -hydroxyprogesterone to form dehydroepiandrosterone and androstenedione respectively. The modulation of these two activities occurs through cytochrome b 5 . Association of cytochrome b 5 and CYP17 is thought to be based primarily on electrostatic interactions in which the negatively charged residues pair up with positively charged residues on the proximal surface of the CYP17 molecule. Non-specific interactions of the hydrophobic membrane regions of cytochrome b 5 and CYP17 are also thought to play a crucial role in the association of these two haemoproteins. Although cytochrome b 5 is known to stimulate CYP activity by contributing the second electron in the catalytic cycle, in the case of CYP17, the mechanism of cleavage stimulation proceeds via an allosteric mode. It is hypothesised that cytochrome b 5 promotes the cleavage by aligning the iron-oxygen complex attack onto the C 20 rather than the C 17 atom of the steroid substrate molecule. Thus, further understanding of the mechanism of modulation by cytochrome b 5 of the hydroxylase and lyase activities should shed new insights on developing therapeutic targets in CYP17-linked biochemical processes such as adrenarche, polycystic ovary syndrome and prostate cancer.

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“…Although cytb 5 is only capable of donating the second electron due to its high redox potential as compared with ferric P450, it plays a key role in the P450 enzyme system in the catalysis of a variety of compounds and significantly regulates the functional activities of P450s (31,32). It is reported that cytb 5 could stimulate, inhibit, or have no effect on P450 activities, depending on the P450 isozyme studied, the substrate involved, or the particular experimental conditions employed (33)(34)(35)(36).…”

mentioning

confidence: 99%

Effects of Membrane Mimetics on Cytochrome P450-Cytochrome b5 Interactions Characterized by NMR Spectroscopy

Zhang

Huang

et al. 2015

Journal of Biological Chemistry

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Background:The functional activities of membrane-bound cytochrome P450s (P450s) are affected by lipids. Results: Stronger interactions between P450 2B4 (CYP2B4) and cytochrome b 5 (cytb 5 ) are observed in bicelles as compared with lipid-free solution or micelles. Conclusion: Lipid bilayers enhance the interaction between CYP2B4 and cytb 5 . Significance: The findings provide insights into the important role of membrane in P450-cytb 5 complex formation.

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The role of cytochrome b5 in adrenal microsomal steroidogenesis

Cited by 88 publications

References 29 publications

Regulation of 17,20 Lyase Activity by Cytochrome b5 and by Serine Phosphorylation of P450c17

Regulation of 17,20 Lyase Activity by Cytochrome b5 and by Serine Phosphorylation of P450c17

Cytochrome b5 modulation of 17α hydroxylase and 17–20 lyase (CYP17) activities in steroidogenesis

Effects of Membrane Mimetics on Cytochrome P450-Cytochrome b5 Interactions Characterized by NMR Spectroscopy

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