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31. |
Modulation of the Polycycuc Aromatic Hydrocarbon-Dependent Induction of Cytochrome P450ia1 By Glucocorticoids |
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Drug Metabolism Reviews,
Volume 20,
Issue 2-4,
1989,
Page 585-599
ProughR. A.,
SherrattA. J.,
BanetD. E.,
LinderM. W.,
MathisJ. M.,
SimpsonE. R.,
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ISSN:0360-2532
DOI:10.3109/03602538909103563
出版商:Taylor&Francis
年代:1989
数据来源: Taylor
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32. |
Use of Bile Fistulas to Solve Problems of Drug Metabolism |
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Drug Metabolism Reviews,
Volume 20,
Issue 2-4,
1989,
Page 601-613
CooperDavid y.,
LevinSidney s.,
SchleyerHeinz,
ManiaraWieslawa,
HuangRong,
MukherjiBiswanath,
SloviterHenry A.,
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ISSN:0360-2532
DOI:10.3109/03602538909103564
出版商:Taylor&Francis
年代:1989
数据来源: Taylor
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33. |
Degradation of Rat Hepatic Cytochrome P-450p |
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Drug Metabolism Reviews,
Volume 20,
Issue 2-4,
1989,
Page 615-628
CorreiaMaria Almira,
SugiyamaKatsumi,
YaoKunquan,
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摘要:
AbstractThe hepatic microsomal hemoproteins, collectively known as cytochrome P-450 (P-450),‡are a family of isozymes committed to metabolism of various structurally diverse substrates to polar, readily excretable products. Although most of these enzyme-substrate interactions are productive in nature, it is now apparent that certain substrates, in the course of their metabolism by cytochrome P-450 isozymes, result in mechanism-based inactivation of the enzyme [1]. For instance, oxidative metabolism of olefinic and acetylenic compounds such as allylisopropylacetamide (AIA), secobarbital, ethinylestradiol, and even ethylene or acetylene result in drug-mediated alkylation of the pyrrolic nitrogen of the prosthetic heme moiety of P-450 to yield a telltale greenish pigment, the N-alkylated heme, thereby inactivating the hemoprotein. On the other hand, compounds such as chloramphenicol, 1-ethynylpyrene, and 10-undecynoic acid appear to inactivate the enzyme by alkylating the apoprotein, also in a mechanism-based process [2-4]. Consistent with this observation, the characteristic hemoprotein chromophore is retained intact, while the enzyme is functionally inactivated. Indeed, we have recently shown that metabolism of secobarbital by the phenobarbital (PB)-inducible rat hepatic P-450b isozyme partitions between prosthetic heme 7V-alkylation, apoprotein alkylation, and epoxidation of the drug [5]. More recently, another form of drug-mediated P-4S0 inactivation has been described. Such inactivation apparently involves drug-mediated activation of the prosthetic heme moiety to (a) reactive species that alkylate(s) the apocytochrome apparently at the active site, and thereby inactivate(s) the enzyme. Such an event was first reported by Guengerich and co-workers [6, 7]to occur during cumene hydroperoxide (CuOOH)-supported oxidation of P-450b as well as NADPH-catalyzed P-450b turnover in the absence of substrates. Irreversible binding of the heme to the apoprotein apparently accounted for 30-60% of the P-450 loss, while polar monopyrrolic and dipyrrolic products were reported to account for the remainder [7]. Subsequently, Pohl and co-workers [8-10]reported that metabolism of carbon tetrachloride and several other P-450 substrates also resulted in similar inactivation of membrane-bound or purified rat liver microsomal P-450b. We have also reported that the one-electron ox-idizable substrates such as 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-l,4-di-hydropyridine (DDEP) and spironolactone also resulted in such inactivation of P-450, and that the dexamethasone (DEX)-inducible isozymes (collectively referred to as P-450p* were particularly susceptible to such inactivation [11, 12]. In contrast, we have found that the 4-aryl dihydropyridines (nifedipine or nitrendipine), although excellent substrates of P-450p, do not result in either its destruction or heme alkylation of its apocytochrome whereas substrates such as AIA, while irreversibly inactivating P-450p, also do not result in appreciable heme-alkylation of the apocytochrome.
ISSN:0360-2532
DOI:10.3109/03602538909103565
出版商:Taylor&Francis
年代:1989
数据来源: Taylor
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34. |
Does Cytochrome P-450 Mediate the Effects of Norepinephrine in the Hepatocyte? |
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Drug Metabolism Reviews,
Volume 20,
Issue 2-4,
1989,
Page 629-643
HoltzmanJordan l.,
PrasadJargarlapudi S.,
EricksonRichard r.,
QainNeng,
XiuYu,
SrivastavaSri Prakash,
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ISSN:0360-2532
DOI:10.3109/03602538909103566
出版商:Taylor&Francis
年代:1989
数据来源: Taylor
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35. |
Design of Specific Mechanism Based Inactivators of Hepatic and Adrenal Microsomal Cytochromes P-450 Responsible for Progesterone 21-Hydroxylation |
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Drug Metabolism Reviews,
Volume 20,
Issue 2-4,
1989,
Page 645-655
HalpertJames r.,
YanJohn,
JohnsonEric F.,
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ISSN:0360-2532
DOI:10.3109/03602538909103567
出版商:Taylor&Francis
年代:1989
数据来源: Taylor
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36. |
Cutaneous Cytochrome P-450 |
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Drug Metabolism Reviews,
Volume 20,
Issue 2-4,
1989,
Page 657-673
MukhtarHasan,
KhanWasiuddin A.,
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ISSN:0360-2532
DOI:10.3109/03602538909103568
出版商:Taylor&Francis
年代:1989
数据来源: Taylor
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37. |
Symposium Scenes |
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Drug Metabolism Reviews,
Volume 20,
Issue 2-4,
1989,
Page 675-677
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ISSN:0360-2532
DOI:10.3109/03602538909103569
出版商:Taylor&Francis
年代:1989
数据来源: Taylor
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38. |
New Perspectives in Catalase Dependent Ethanol Metabolism |
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Drug Metabolism Reviews,
Volume 20,
Issue 2-4,
1989,
Page 679-688
ThurmanRonald g.,
HandlerJeffrey a.,
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ISSN:0360-2532
DOI:10.3109/03602538909103570
出版商:Taylor&Francis
年代:1989
数据来源: Taylor
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39. |
Udp-Glucuronosyltrans-Ferases in the Metabolic Disposition of Xenobiotics |
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Drug Metabolism Reviews,
Volume 20,
Issue 2-4,
1989,
Page 689-695
TephlyThomas r.,
TownsendMarcy,
GreenMitchell D.,
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ISSN:0360-2532
DOI:10.3109/03602538909103571
出版商:Taylor&Francis
年代:1989
数据来源: Taylor
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40. |
Xen0biotic Oxidation Catalyzed by Aldehyde Dehydrogenases |
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Drug Metabolism Reviews,
Volume 20,
Issue 2-4,
1989,
Page 697-720
Sladek.N. E.,
MantheyC. L.,
MakiP. A.,
ZhangZ.,
LandkamerG. J.,
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ISSN:0360-2532
DOI:10.3109/03602538909103572
出版商:Taylor&Francis
年代:1989
数据来源: Taylor
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