PubMed Health⌕ Search

Biomedical subjects

E Maser

Publications and source records attributed to E Maser.

64 records · Page 4Linked to original sources
PubMed1991

Heterogeneity of carbonyl reduction in subcellular fractions and different organs in rodents.

The pattern and distribution of carbonyl reduction in liver, kidney and adrenal gland subcellular fractions of NMRI mice, Wistar rats and Hartley guinea pigs were examined using the ketone compound metyrapone (2-methyl-1,2-di(3-pyridyl)1-propanone) commonly used as a diagnostic cytochrome P450 inhibitor. A direct HPLC method for alcohol metabolite determination instead of the indirect spectrophotometric recording of pyridine nucleotide oxidation at 340 nm was applied. All the tissues examined in these species rapidly reduced the employed compound but at the subcellular level no general distribution scheme of specific activity was found, although in all fractions metyrapol formation could be attributed to aldo-keto reductases. Cytosolic and microsomal metyrapone reducing enzymes are distinguished by their inhibitor sensitivity to phenobarbitone and quercitrin and thus can be characterized as aldehyde and ketone reductases according to the inhibitor subclassification of the aldo-keto reductase family. Moreover, the enzymes also differ with respect to their immunological cross-reactivity to anti-microsomal mouse liver metyrapone reductase antibodies. Immunological homologies were found between metyrapone reductases of liver microsomes from all species and kidney and adrenal gland microsomes from guinea pig. However, the protein of all the cytosolic fractions as well as that of kidney and adrenal gland microsomes from mouse and rat did not cross-react with the antibodies, indicating the absence of common antigenic determinants. From catalytic properties and functional data it is concluded that hydroxysteroid dehydrogenases present in the suspected subcellular fractions form a structurally and functionally related enzyme family which may have been conserved during evolution.

Adrenal Glands↗
PubMed1991

Reductive metabolism of metyrapone by a quercitrin-sensitive ketone reductase in mouse liver cytosol.

Mouse liver cytosol catalyses the reduction of metyrapone to the corresponding alcohol metabolite metyrapol. The enzyme involved was characterized as a NADPH-dependent carbonyl reductase which is strongly inhibited by the plant flavonoid quercitrin but which shows no sensitivity to phenobarbital. Thus, by inhibitor subdivision of carbonyl reductases the metyrapone reductase in mouse liver cytosol has to be classified as a ketone reductase rather than an aldehyde reductase, as it was shown previously for the analogous enzyme in mouse liver microsomes based on the same pattern of inhibitor classification. Moreover, immunological comparison of the metyrapone reductases from the two subcellular fractions reveal no common antigenic determinants indicating the structural difference between these enzymes. In conclusion, metyrapone undergoes reductive biotransformation mediated by two clearly distinct carbonyl reductases located in different subcellular compartments of mouse liver cells. Considering the convenient and sensitive HPLC-method for direct metyrapol determination, metyrapone may serve as a useful tool in the investigation of these enzymes, although their physiological roles remain to be determined.

Alcohol Oxidoreductases↗
PubMed1991

The occurrence of carbonyl reduction in continuous cell lines emphasizes the essentiality of this metabolic pathway.

Using the ketone compound metyrapone (MPON) as a substrate for carbonyl reduction it has been verified for the first time that various permanent cell lines in culture express carbonyl reducing activity. This is even true for the dedifferentiated and fibroblastoid cell line V79, emphasizing the essentiality of this metabolic pathway. MPON reducing enzyme activities are located in the endoplasmic reticulum as well as in the cytoplasm of the cells. Compared to MPON-reductase in rat liver microsomes, no immunological homology to microsomal C2REV7 rat liver hepatoma cell MPON-reductase could be detected, indicating differences in antigenic determinants between the enzymes of the solid organ and respective cells in continuous culture.

Animals↗
PubMed1989

Purification and properties of a metyrapone-reducing enzyme from mouse liver microsomes--this ketone is reduced by an aldehyde reductase.

A ketone reducing enzyme was purified to homogeneity from female mouse liver microsomes, using the diagnostic cytochrome P-450 inhibitor metyrapone as a substrate. In contrast to the usually employed indirect spectrophotometric recording of pyridine nucleotide oxidation at 340 nm, a HPLC method was applied for direct alcohol metabolite determination. Purification of the carbonyl reductase resulted in a 360-fold increase in specific activity together with a single band in the 34 kD region after SDS-polyacrylamide gel electrophoresis. Phenobarbital, indomethacin, dicoumarol and 5 alpha-dihydrotestosterone inhibited the enzyme, whereas quercitrin did not affect the enzyme activity. Thus, by inhibitor classification of carbonyl reductases the ketone metyrapone is reduced by an aldehyde reductase, rather than by a ketone reductase. Dihydrotestosterone, the strongest inhibitor, is supposed to be the physiological substrate for the purified enzyme. It was demonstrated that during the steps of purification both NADPH and NADH can supply the required reducing equivalents, although the activity with NADH is weaker. The highest activity was obtained using an NADPH-regenerating system. Ethanol and the nonionic detergent Emulgen 913 led to an increased specific activity, indicating that the enzyme is bound to the membranes of the endoplasmic reticulum in a latent state. From these results it is concluded that the microsomal metyrapone-reducing enzyme belongs to the family of carbonyl reductases, but differs from the common patterns of their classification with regard to cofactor requirement and inhibitor susceptibility.

Alcohol Dehydrogenase↗
PubMed1987

The 14CO2 breath test: facilities and limitations of a rapid and noninvasive method for in vivo evaluation of modified hepatic cytochrome P-450--a critique.

By means of the breath test technique the cascade from O-demethylations to CO2 was investigated after pretreatment of mice with warfarin, phenobarbital, cobaltous chloride, sodium vanadate and metyrapone. It was the intention to examine the validity of the technique with respect to cytochrome P-450 activity. Therefore three different radioactive labeled substrates, i.e., hydrogen carbonate, formate and xenobiotics, were applied at three different levels of the one-carbon pathway and were utilized to demonstrate possible interference of the modifiers with the sequence from O-demethylation to CO2. Real in vivo information about a modified cytochrome P-450 system can be obtained using model substrates carefully selected with regard to the type of expected modification of the monooxygenase system. In addition, a parallel monitoring of the consecutive reaction sequence by measuring the conversion of formate to CO2 is necessary in order to guarantee the validity of the in vivo technique in visualizing the activity of the hepatic monooxygenase system.

Animals↗
PubMed1985

Alteration of the inhibitory effect of metyrapone by reduction to metyrapol during the metabolism of methacetin in vivo in mice.

Metyrapone is known as an inhibitor of the oxidative drug metabolism in vitro. We have used the exhalation analysis as a tool to study the influence of this inhibitor on the demethylation of 14C-methacetin in vivo. In parallel we investigated the reductive metabolism of metyrapone in mice by measuring the concentrations of metyrapone and its reduced metabolite metyrapol with a HPLC-method. 50 mg of metyrapone/kg b. wt. resulted in a 90% inhibition of 14CO2 exhalation when given 2 min before the exhalation analysis was started. The prolongation of the intervals between i.p. metyrapone and substrate administration leads to a diminution of the in vivo inhibition. We found that the hepatic metyrapone concentration falls rapidly and passes the detection limit at 120 min. Transiently metyrapol reaches a maximal concentration 15 min after the application of metyrapone. The rapid reduction of metyrapone was confirmed in vitro with fresh mouse liver homogenates. The administration of metyrapol itself in vivo causes a decrease in 14CO2 exhalation, too. The 14CO2 exhalation curves after metyrapol correspond to the curves after metyrapone, when sufficient time was allowed for its reduction to metyrapol. It can be concluded that not only metyrapone itself but also its reductive metabolite metyrapol is an effective, however weaker inhibitor.

7-Alkoxycoumarin O-Dealkylase↗
PubMedDate not supplied

Changes in patient perception and behavior following Mohs micrographic surgery.

BACKGROUND: Mohs micrographic surgery (MMS) is used for the removal of difficult or recurrent skin cancer. Little is known about the behavioral changes of patients who have undergone this procedure. OBJECTIVE: This study was conducted to document patients' long-term psychological and behavioral changes following MMS. METHODS: A survey was mailed to a sample of 260 persons who underwent the Mohs procedure in 1997. It included questions on sunscreen use, level of anxiety about cancer, patient confidence in MMS, and changes in high-risk habits. RESULTS: The study included 214 patients who responded to our mailed questionnaire. Trends showed an increase in some but not all preventative measures taken to avoid skin cancer recurrence post-MMS. Other healthy lifestyle changes, such as decreased cigarette smoking, were not noted. CONCLUSION: Mohs micrographic surgery has an impact on some aspects of patients' health-related behavior, especially skin cancer prevention. Other aspects which are not affected may be targets for extra patient education.

Adult↗