scholarly journals 4,4′-dimethylcholesta-7,9,14-trienol is an intermediate in the demethylation of dihydroagnosterol

1977 ◽  
Vol 166 (1) ◽  
pp. 17-20 ◽  
Author(s):  
I A F Tavares ◽  
K A Munday ◽  
D C Wilton
Keyword(s):  
Rat Liver ◽  
Liver Homogenate ◽  
Anaerobic Conditions ◽  
Microsomal Preparation ◽  
Aerobic Conditions ◽  
Liver Microsomal Preparation

1. 4,4′-Dimethylcholesta-7,9,14-trienol is an intermediate in the metabolism of dihydroagnosterol to cholesterol by rat liver homogenate. 2. This triene is reduced by a rat liver microsomal preparation in the presence of NADPH to give 4,4′-dimethylcholesta-7,9-dienol under anaerobic conditions. 3. Reduction of the triene in the presence of [4-3H2]NADPH resulted in the incorporation of 3H into the product. 4. Under aerobic conditions the triene is converted into cholesterol by a rat liver homogenate.

scholarly journals Cyclic metabolic pathway of a butylated hydroxytoluene by rat liver microsomal fractions

1974 ◽  
Vol 144 (3) ◽  
pp. 497-501 ◽  
Author(s):  
C Chen ◽  
Y S Shaw
Keyword(s):  
Rat Liver ◽  
Metabolic Pathway ◽  
Butylated Hydroxytoluene ◽  
High Efficacy ◽  
Microsomal Preparation ◽  
Liver Microsomal Preparation

A cyclic metabolic pathway was obtained when 3,5-di-t-butyl-4-hydroxytoluene (BHT) was incubated with a rat liver microsomal preparation. The pathway is as follows: BHT → 4-hydroperoxy-4-methyl-2,6-di-t-butylcyclohexa-2,5-dienone (BHT-OOH) → 4-hydroxy-4-methyl-2,6-di-t-butylcyclohexa-2,5-dienone (BHT-30OH) → BHT. This metabolic pathway suggests that antioxidants such as BHT owe their high efficacy, at least in part, to their metabolic regeneration.

Drug-metabolizing activity of the human placenta

1968 ◽  
Vol 46 (9) ◽  
pp. 1057-1061 ◽  
Author(s):  
G. R. Van Petten ◽  
G. H. Hirsch ◽  
A. D. Cherrington
Keyword(s):  
Rat Liver ◽  
Human Placenta ◽  
Supernatant Fraction ◽  
Drug Metabolizing Enzymes ◽  
Microsomal Preparation ◽  
Metabolizing Enzymes ◽  
Liver Microsomal Preparation ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Nitroreductase Activity ◽  
Human Placentae

The drug-metabolizing activity of a 9000 × g supernatant fraction prepared from human placentae obtained immediately after birth was investigated. For comparative purposes a similar rat liver microsomal preparation was used. The metabolism of pentobarbital by oxidation, and of amphetamine by deamination or hydroxylation, proceeded at similar rates in the two tissues. The rate of metabolism of meperidine in the human placental preparation was about two-thirds of that found with the rat liver enzyme. The rate of metabolism of aminopyrine, as determined by measuring the formation of 4-aminoantipyrine or the production of formaldyhyde, was insignificant in the placental preparation, but the metabolism of 4-aminoantipyrine occurred much more rapidly in this tissue than in rat liver. The nitroreductase activity of the human placenta was low; a sixfold activation was achieved by adding a source of glucose 6-phosphate dehydrogenase but the activity was still only one-third of that found in rat liver. The cofactor requirements for the drug-metabolizing enzymes studied were found to be similar in the two tissues. The significance of these findings with respect to the effects of drugs on the mother and the fetus is discussed.

scholarly journals The nature of the acid-volatile selenium in the liver of the male rat

1973 ◽  
Vol 134 (1) ◽  
pp. 283-293 ◽  
Author(s):  
A. T. Diplock ◽  
Christine P. J. Caygill ◽  
Elizabeth H. Jeffery ◽  
C. Thomas
Keyword(s):  
Vitamin E ◽  
Rat Liver ◽  
Microsomal Fraction ◽  
Current Knowledge ◽  
Liver Homogenate ◽  
Selenium Deficiency ◽  
Male Rat ◽  
Anaerobic Conditions ◽  
Volatile Material ◽  
Acid Labile

1. The properties of rat liver acid-volatile selenium have been compared with those of H2Se and (CH3)2Se. 2. In model experiments oxidation-sensitive H275Se was trapped quantitatively under anaerobic conditions in 0.1m-AgNO3, and (CH3)275Se was trapped quantitatively in 8m-HNO3. The acid-labile selenium of a liver homogenate, and of a microsomal fraction, was found to behave quite unlike (CH3)275Se and in a manner indistinguishable from H275Se. 3. It was concluded that the acid-volatile material is certainly not (CH3)2Se and that it is probably H2Se. 4. The significance of these findings is discussed in relation to current knowledge about the metabolism and detoxication of selenium, and a scheme is proposed which incorporates this knowledge with recent observations on the interactions between trace amounts of selenium and tocopherol, and the production of acute selenium deficiency by Ag+ in vitamin E-deficient rats.

scholarly journals A novel olefinic rearrangement. The enzymic conversion of cholesta-7,9-dien-3β-ol into cholesta-8,14-dien-3β-ol

1972 ◽  
Vol 129 (2) ◽  
pp. 225-229 ◽  
Author(s):  
M. Akhtar ◽  
C. W. Freeman ◽  
A. D. Rahimtula ◽  
D. C. Wilton
Keyword(s):  
Rat Liver ◽  
Liver Homogenate ◽  
High Yield ◽  
Supernatant Fraction ◽  
Anaerobic Conditions

1. [3α-3H]Cholesta-7,9-dien-3β-ol is converted in high yield into cholesterol by a 10000gav. supernatant fraction of rat liver homogenate. 2. Incubation of cholesta-7,9-dien-3β-ol with [4-3H]NADPH and rat liver microsomal fractions under anaerobic conditions resulted in3H being incorporated into the 14α-position of cholest-7-en-3β-ol. 3. Under anaerobic conditions in the absence of NADPH cholesta-7,9-dien-3β-ol was isomerized into cholesta-8,14-dien-3β-ol by rat liver microsomal fractions.

scholarly journals Studies on the mechanism and regulation of C-4 demethylation in cholesterol biosynthesis. The role of adenosine 3′:5′-cyclic monophosphate

1971 ◽  
Vol 125 (2) ◽  
pp. 625-634 ◽  
Author(s):  
D. P. Bloxham ◽  
D. C. Wilton ◽  
M. Akhtar
Keyword(s):  
Cholesterol Biosynthesis ◽  
Competitive Inhibitor ◽  
Microsomal Preparation ◽  
Aerobic Conditions ◽  
Dehydrogenase Enzyme ◽  
Labelled Compound ◽  
Nad 4 ◽  
Liver Microsomal Preparation ◽  
Compound Ii

1. An assay for demethylation has been developed based on the release of tritium from 4,4-dimethyl[3α-3H]cholest-7-en-3β-ol (II). 2. The maximum release of 3H from 3α-3H-labelled compound (II) in a rat liver microsomal preparation occurs in the presence of NADPH and NAD+ under aerobic conditions. 3. Incubation of 3α-3H-labelled compound (II) with NADPH under aerobic conditions leads to the formation of a 3α-3H-labelled C-4 carboxylic acid. This compound undergoes dehydrogenation on subsequent anaerobic incubation with NAD+. 4. The 3H released from the steroid was located in [4-3H]nicotinamide and the medium. Incubation with synthetic [4-3H2]NADH gave a similar result. 5. In the presence of glutamate dehydrogenase and α-oxoglutarate part of the 3H released from the steroid was transferred to glutamate. 6. A series of 3-oxo steroids were reduced equally well by [4-3H2]NADH and [4-3H2]NADPH. The reduction of 5α-cholest-7-en-3-one was shown to use the 4B H atom from the nucleotide. 7. 3′:5′-Cyclic AMP was shown to be a competitive inhibitor of the 3β-hydroxy dehydrogenase enzyme in the demethylation reaction.

The Reaction of Thiol Compounds with the Vitamin-K Dependent Clotting Factors

1969 ◽  
Vol 21 (03) ◽  
pp. 573-579 ◽  
Author(s):  
P Fantl
Keyword(s):  
Prothrombin Time ◽  
Vitamin K ◽  
Anaerobic Conditions ◽  
Clotting Factors ◽  
Thiol Compounds ◽  
Aerobic Conditions ◽  
One Stage ◽  
Factor Ii ◽  
Ph Dependent ◽  
The One

SummaryTreatment of human and dog oxalated plasma with 0.2 to 1.0 × 10−1 M 2.3-dithiopropanol (BAL) or dithiothreitol (DTT) at 2–4° C for 30 min results in the reduction of the vitamin-K dependent clotting factors II, VII, IX and X to the respective-SH derivatives. The reaction is pH dependent. Under aerobic conditions the delayed one stage prothrombin time can be partly reversed. Under anaerobic conditions a gradual prolongation of the one stage prothrombin time occurs without reversal.In very diluted plasma treated with the dithiols, prothrombin can be converted into thrombin if serum as source of active factors VII and X is added. In contrast SH factors VII, IX and X are inactive in the specific tests. Reoxidation to active factors II, VII, IX and X takes place during adsorption and elution of the SH derivatives. The experiments have indicated that not only factor II but also factors VII, IX and X have active-S-S-centres.

METABOLISM OF 17α-HYDROXYPROGESTERONE-4-14C-17α-CAPROATE BY HOMOGENATES OF RAT LIVER AND HUMAN PLACENTA

1961 ◽  
Vol 36 (4) ◽  
pp. 511-519 ◽  
Author(s):  
Margaret Wiener ◽  
Charles I. Lupa ◽  
E. Jürgen Plotz
Keyword(s):  
Rat Liver ◽  
Human Placenta ◽  
Steric Hindrance ◽  
Placental Tissue ◽  
Caproic Acid ◽  
Major Product ◽  
Side Chain ◽  
Anaerobic Conditions ◽  
Prolonged Action ◽  
Long Acting

ABSTRACT 17α-hydroxyprogesterone-4-14C-17α-caproate (HPC), a long-acting progestational agent, was incubated with homogenates of rat liver and human placenta. The rat liver was found to reduce Ring A of HPC under anaerobic conditions to form allopregnane-3β,17α-diol-20-one-17α-caproate and pregnane-3β,17α-diol-20-one-17α-caproate, the allopregnane isomer being the major product. The caproic acid ester was neither removed nor altered during the incubation. Placental tissue did not attack HPC under conditions where the 20-ketone of progesterone was reduced. It is postulated that this absence of attack on the side chain is due to steric hindrance from the caproate ester, and that this may account for the prolonged action of HPC.

scholarly journals Biotransformation of Timosaponin BII into Seven Characteristic Metabolites by the Gut Microbiota

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3861
Author(s):  
Guo-Ming Dong ◽  
Hang Yu ◽  
Li-Bin Pan ◽  
Shu-Rong Ma ◽  
Hui Xu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Rat Liver ◽  
Pharmacological Activity ◽  
Liver Homogenate ◽  
Intestinal Flora ◽  
Important Indicator ◽  
Metabolic Characteristics ◽  
Metabolic Behavior ◽  
First Time ◽  
Rat Liver Microsome

Timosaponin BII is one of the most abundant Anemarrhena saponins and is in a phase II clinical trial for the treatment of dementia. However, the pharmacological activity of timosaponin BII does not match its low bioavailability. In this study, we aimed to determine the effects of gut microbiota on timosaponin BII metabolism. We found that intestinal flora had a strong metabolic effect on timosaponin BII by HPLC-MS/MS. At the same time, seven potential metabolites (M1-M7) produced by rat intestinal flora were identified using HPLC/MS-Q-TOF. Among them, three structures identified are reported in gut microbiota for the first time. A comparison of rat liver homogenate and a rat liver microsome incubation system revealed that the metabolic behavior of timosaponin BII was unique to the gut microbiota system. Finally, a quantitative method for the three representative metabolites was established by HPLC-MS/MS, and the temporal relationship among the metabolites was initially clarified. In summary, it is suggested that the metabolic characteristics of gut microbiota may be an important indicator of the pharmacological activity of timosaponin BII, which can be applied to guide its application and clinical use in the future.

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