scholarly journals Conversion of 19-oxo[2β-2H]androgens into oestrogens by human placental aromatase. An unexpected stereochemical outcome

1990 ◽  
Vol 268 (3) ◽  
pp. 553-561 ◽  
Author(s):  
P A Cole ◽  
C H Robinson
Keyword(s):  
Active Site ◽  
Extended Period ◽  
Direct Role ◽  
Methyl Group ◽  
Enzyme Active Site ◽  
Model Studies ◽  
The Third ◽  
Intensive Investigation ◽  
Cytochrome P 450

Aromatase is a cytochrome P-450 enzyme that catalyzes the conversion of androgens into oestrogens via sequential oxidations at the 19-methyl group. Despite intensive investigation, the mechanism of the third step, conversion of the 19-aldehydes into oestrogens, has remained unsolved. We have previously found that a pre-enolized 19-al derivative undergoes smooth aromatization in non-enzymic model studies, but the role of enolization by the enzyme in transformations of 19-oxoandrogens has not been previously investigated. The compounds 19-oxo[2 beta-2H]testosterone and 19-oxo[2 beta-2H]androstenedione have now been synthesized. Exposure of either of these compounds to microsomal aromatase, in the absence of NADPH, for an extended period led to no significant 2H loss or epimerization at C-2, leaving open the importance of an active-site base. However, in the presence of NADPH there was an unexpected substrate-dependent difference in the stereoselectivity of H loss at C-2 in the enzyme-induced aromatization of 19-oxo[2 beta-2H]-testosterone versus 19-oxo[2 beta-2H]androstenedione. The aromatization results for 17 beta-ol derivative 19-oxo[2 beta-2H]-testosterone correspond to about 1.2:1 2 beta-H/2 alpha-H loss from unlabelled 19-oxotestosterone. In contrast, aromatization results for 19-oxo[2 beta-2H]androstenedione correspond to at least 11:1 2 beta-H/2 alpha-H loss from unlabelled 19-oxoandrostenedione. This substrate-dependent stereoselectivity implies a direct role for an enzyme active-site base in 2-H removal. Furthermore, these results argue against the proposal that 2 beta-hydroxylation is the obligatory third step in aromatase action.

Late Roman Precious-Metal Deposits: Worth their Weight in Gold?

Britannia ◽  
2012 ◽  
Vol 43 ◽  
pp. 427-430
Author(s):  
François Baratte
Keyword(s):  
Late Antiquity ◽  
Precious Metal ◽  
Extended Period ◽  
Third Century ◽  
The Third ◽  
Byzantine Period ◽  
The Subject ◽  
Title One ◽  
Late Roman

Over recent years the question of ancient hoards, in particular of precious metal, coins, plate or jewellery, has been the subject of numerous considerations (notably S. Gelichi and C. La Rocca (eds), Tesori. Forme di accumulazione della richezza nell'alto medioevo (secoli V–XI) (Rome, 2004)) in order to try to grasp the characteristics of a complex phenomenon that relates to multiple aspects of society in whatever period is under consideration: the economy, social organisation, the possible role of the images … The difficulties encountered by researchers when addressing these problems are illustrated by the ambivalence, indeed the ambiguity in many languages of the term ‘trésor/hoard’. Richard Hobbs has thus chosen, very judiciously, to take as his subject here ‘deposits of precious metal’, which defines the topic perfectly. On the other hand, one could question the descriptor ‘late Roman’ when applied to the period covered here, five centuries, from a.d. 200 to 700. There could be discussion over whether the third century should be included in Late Antiquity; others will challenge whether the sixth century still belongs to that same world. But from the first page H. effectively corrects his title by stating that it also covers the early Byzantine period, something I would feel is a better definition. It may certainly be felt that these are just questions of nomenclature, but they do have their importance for the topic of this study. All the same, the important thing is that H. wanted to study an extended period, as stated by the book's sub-title. One cannot but approve of his choice.

Lipase activation by molecular bioimprinting: The role of interactions between fatty acids and enzyme active site

2020 ◽  
Author(s):  
Luma M. de S. Brandão ◽  
Milson S. Barbosa ◽  
Ranyere L. Souza ◽  
Matheus M. Pereira ◽  
Álvaro S. Lima ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Active Site ◽  
Enzyme Active Site

Endothelin is a potent constrictor of the lamb ductus arteriosus

1989 ◽  
Vol 67 (8) ◽  
pp. 902-904 ◽  
Author(s):  
Flavio Coceani ◽  
Craig Armstrong ◽  
Lois Kelsey
Keyword(s):  
Contractile Response ◽  
Ductus Arteriosus ◽  
Extended Period ◽  
Cytochrome P 450

Endothelin was tested on isolated ductus arteriosus preparations from mature fetal Iambs. At low [Formula: see text] (18–24 Torr; 1 Torr = 133.3 Pa), the compound constricted the vessel dose-dependently over the range from about 10−10 to 10−7 M. The contraction was sustained and did not subside even after an extended period of washing. Endothelin was also effective on tissues ([Formula: see text], 217–231 Torr; indomethacin, 2.8 × 10−6 M) that had been completely relaxed with CO (CO/O2 ratio, 0.28). CO treatment interferes with a cytochrome P-450 mechanism, which is considered crucial for the contractile response of the vessel to oxygen. These findings are consistent with a role of endothelin in the closure of the ductus arteriosus at birth.Key words: ductus arteriosus closure, oxygen, cytochrome P-450.

Author response for "Lipase activation by molecular bioimprinting: The role of interactions between fatty acids and enzyme active site"

2020 ◽  
Author(s):  
Luma M. de S. Brandão ◽  
Milson S. Barbosa ◽  
Ranyere L. Souza ◽  
Matheus M. Pereira ◽  
Álvaro S. Lima ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Active Site ◽  
Author Response ◽  
Enzyme Active Site
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