50-22-6Relevant articles and documents
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Bernstein,Lenhard
, p. 2331 (1955)
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IN VITRO ADRENAL BIOACTIVATION AND EFFECTS ON STEROID METABOLISM OF DDT, PCBs AND THEIR METABOLITES IN THE GRAY SEAL (HALICHOERUS GRYPUS)
Lund, Bert-Ove
, p. 911 - 918 (1994)
The irreversible binding of the DDT metabolites o, p'-DDD and MeSO2-DDE, as well as their potential to inhibit mitochondrial steroid 11β-hydroxylation in the gray seal adrenal gland, was studied. The adrenal bioactivated both o, p'-DDD and MeSO2 -DDE in vitro. The irreversible binding of o, p'-DDD was, however, 17 times higher than that of MeSO2- DDE. In both cases, the enzymes responsible for the activation resided primarily in mitochondria, and inhibitory effects of cytochrome P450 inhibitors (metyrapone and SKF 525A) and NADPH omission indicated mitochondrial P450 enzymes as responsible for the bioactivation. Forty-micromolar concentrations of o, p'-DDD and p, p'-DDT inhibited 11β-hydroxylation of glucocorticoids (10μM) by approximately 25 percent. In contrast, none of the studied compounds - MeSO2-DDE, p, p'-DDE, some PCBs, and methylsulfonyl-PCBs (40 μM) - affected the mitochondrial 11β-hydroxylase activity. Bioactivation of environmental pollutants such as DDT and PCB metabolites and inhibition of P450 11β-hydroxylase are discussed as possible reasons for the generation of the adrenocortical hyperplasia observed in Baltic seals. - Keywords: DDT; DDD; Methylsulfonyl-DDE; Seal adrenal; 11β-Hydroxylase.
Functional interactions of adrenodoxin with several human mitochondrial cytochrome P450 enzymes
Barckhausen, Ian R.,Child, Stella A.,Glass, Sarah M.,Goldfarb, Margo H.,Guengerich, F. Peter,Reddish, Michael J.
, (2020/10/02)
Seven of the 57 human cytochrome P450 (P450) enzymes are mitochondrial and carry out important reactions with steroids and vitamins A and D. These seven P450s utilize an electron transport chain that includes NADPH, NADPH-adrenodoxin reductase (AdR), and adrenodoxin (Adx) instead of the diflavin NADPH-P450 reductase (POR) used by the other P450s in the endoplasmic reticulum. Although numerous studies have been published involving mitochondrial P450 systems, the experimental conditions vary considerably. We compared human Adx and bovine Adx, a commonly used component, and found very similar catalytic activities in reactions catalyzed by human P450s 11B2, 27A1, and 27C1. Binding constants of 6–200 nM were estimated for Adx binding to these P450s using microscale thermophoresis. All P450 catalytic reactions were saturated at 10 μM Adx, and higher concentrations were not inhibitory up to at least 50 μM. Collectively these studies demonstrate the tight binding of Adx (both human and bovine) to AdR and to several mitochondrial P450s and provide guidance for optimization of Adx-dependent P450 reactions.
Raw synthesis and mitochondrial function postischemic mitochondria diseases related to the lack or for use in new compd. 11β-hydroxysteroid
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Paragraph 0278, (2016/10/08)
The present invention provides novel compounds of 112-hydroxy steroids and compositions and their application as pharmaceuticals for preventing or reversing injury to mitochondria, for treating or preventing diseases relating to mitochondrial dysfunction or depletion, and for inducing regeneration or restructuring of mitochondria as a means of treating diseases relating to abnormalities in mitochondrial structure and function in a human or animal subject. Also disclosed herein are methods for diagnosing injury to mitochondria and for diagnosing the success or failure of therapeutics designed to treat, prevent, or reverse injury to or depletion of mitochondria.
