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C Monder

Publications and source records attributed to C Monder.

At least 91 records · Page 5Linked to original sources
PubMed1981

Stimulation of gluconeogenesis by cortisol in fetal rat liver in organ culture.

Fetal rat liver explants (gestational day 20) depleted of glycogen converted L-[14C]alanine into labeled glucose and glycogen. Cortisol 1) stimulated net glyconeogenesis about 2-fold at 22 h of incubation after a 7-h lag; 2) increased the total amount of glycogen in the explant 2-fold; 3) stimulated the net incorporation of label from [14C]alanine into both glucose and glycogen. Both [3H]glucose added to the medium and glucose generated by gluconeogenesis from [14C]alanine contributed to the glycogen formed. Cortisol led to greater 14C uptake than 3H uptake into glycogen. During gluconeogenesis, [14C]glycogen was first formed and subsequently broke down to [14C]glucose. In the absence of cortisol, glucose and glycogen reached equilibrium with each other. In the presence of cortisol, preferential uptake of alanine into glycogen persisted throughout the 22 h of incubation, and equilibrium was not reached. Gluconeogenesis from [14C]glycerol was greater than from [14C]alanine. Cortisol stimulated its conversion to glycogen but not to glucose. It was concluded that gluconeogenesis in fetal rat liver occurs under organ culture conditions, that its stimulation by cortisol is direct and is localized in two regions: conversion of L-alanine to triose phosphates and of glucose-6-phosphate to glycogen.

Alanine↗
PubMed1980

Presence of epimerase activity in hamster liver corticosteroid side chain isomerase.

11-Deoxy-[21-3H]corticosterone ([21-3H]DOC) exchanged tritium with water in a reaction mediated by an enzyme preparation obtained from hamster liver. Both (21S)-[21-3H]- and (21R)-[21-3H]DOC participated in the exchange. Incorporation of tritium into water followed a hyperbolic path with time for the 21S epimer and a sigmoidal path for the 21R epimer. Separate enzymes did not appear to be involved. The system was also studied by measuring incorporation of deuterium from deuterated water into the steroid side chain. During incubation, DOC containing 2, 1, and no deuteria were all found. Their proportions changed with incubation time. The deuterium atoms were incorporated into the side chain sequentially and reversibly. It is proposed that (21S)-[21-3H]DOC directly exchanges tritium with water in a reaction catalyzed by an isomerase, and (21R)-[21-3H]DOC loses tritium only after prior enzyme-mediated epimerization to the 21S form. We had previously presented evidence that the isomerase reversibly converted the ketol side chain to the aldol form. Epimerization of the aldol isomer, 20 beta-hydroxy-3-oxopregn-4-en-21-al (isoDOC) by hamster liver enzyme to the 20 alpha-hydroxy isomer was shown directly. A model is presented which accounts for the kinetics of exchange of (21R)- and (21S)-[21-3H]DOC with water, interconversion of DOC and isoDOC, and the epimerization of isoDOC at C-20.

Animals↗
PubMed1980

Gas chromatographic and mass spectrometric analysis of urinary acidic metabolites of cortisol.

A method is described suitable for the analysis of the urinary acidic metabolites of cortisol which are amongst the major metabolites of this hormone (5-25% of secretion). Following hydrolysis of the urinary glucuronide conjugates and extraction of the freed steroids, methyl ester-trimethylsilyl ethers were prepared for gas chromatographic analysis. This analysis was carried out on open tubular columns coated with Carbowax stationary phase. The polar phase column permitted the complete resolution of the four acidic metabolites: alpha-cortolonic, beta-cortolonic, alpha-cortolic and beta-cortolic acids.

Carboxylic Acids↗
PubMed1980

Acidic metabolites. V. Isosteroids as intermediates in cortoic acid formation.

The role of steroid-17-aldols, 20 beta-isocortisol (11 beta, 17,20 beta-trihydroxy-3-oxo-pregn-4-en-21-al) or 20 beta-iso THE (3 alpha,17,20 beta-trihydroxy-11-oxo-pregnan-21-al), as preferred intermediates for the biosynthesis of cortoic acids was studied in human subjects. The results demonstrated that the isosteroids were converted moe efficiently than cortisol to cortoic acids and hexahydro neutral metabolites. In all cases, the oxidation state at C-11 was largely conserved. After the administration of the 20 beta compounds both 20 alpha and 20 beta epimers of the acidic and neutral metabolites were isolated. This inversion occurred without oxidation at C-20 and provided evidence for the mediation of an epimerase in this transformation. The results further indicate that reversion of the isosteroids to ketolic intermediates (i.e. cortisol, tetrahydrocortisol, and tetrahydrocortisone did not occur.

Carbon Radioisotopes↗
PubMed1978

Purification and properties of an NADPH-dependent 21-oxo-20-hydroxysteroid reductase (17beta-aldol reductase) from sheep liver. Isolation of the 20beta-glycol product.

This investigation was undertaken to test the hypothesis that steroidal 20-hydroxy-21-aldehydes are intermediates in an alternative pathway of corticosteroid metabolism leading to steroidal 20,21-diols. A NADPH-dependent 21-oxo-20-hydroxysteroid reductase which catalyzed the reduction of 11beta,17,20beta-trihydroxy-3-keto-4-pregnen-21-al (isocortisol) to 11beta,17,20beta,21-tetrahydroxy-4-pregnen-3-one (Reichstein's compound E) was prepared from sheep liver. Other steroidal 17-aldols were also good substrates. Some steroidal 17-oxoaldehydes, D-, and L-glyceraldehyde were reduced, but less effectively than the steroidal aldols. Steroidal ketols and 21-oic acids were not substrates. The enzyme contains--SH groups, has a pH optimum of 6.9 to 7.5 and a molecular weight of about 28,000. Reversibility of the enzymic reaction could not be demonstrated. The reduction product obtained from isocortisol was isolated and characterized. Other 17-glycols were derived from their respective steroid aldols. Reductase activity was also present in hamster and rat liver. From a comparison of 21-oxo-20-hydroxysteroid reductase and 21-hydroxysteroid dehydrogenase with respect to pH optima, substrate specificity, stability to heat, and kinetic constants, we conclude that the two enzymes are distinct.

Animals↗
PubMed1978

Perinatal development of the tyrosine oxidizing system.

The enzymes of the tyrosine oxidase (TO) system of rat liver were measured during pre- and postnatal development. At all ages, the rate of tyrosine oxidation was limited by the activity of tyrosine aminotransferase (TAT). TAT of liver was undetectable from 4 days to 1 day before birth and was lower than p-hydroxyphenylpyruvate oxidase (pHPPO) and homogentisate oxidase (HO) postnatally. At birth, TAT, pHPPO, and HO were 2.9, 13, and 40% of adult values, respectively. Relative levels in fetal liver were HO greater than pHPPO greater than TAT. When enzyme activities were adjusted to compensate for dilution by hematopoietic cells, absolute activities increased, but other relationships remained the same. pHPPO rose at 15-17 days after birth and exceeded adult values at 31 days. HO was unchanged after birth. We conclude that each enzyme of TO follows a unique developmental path, with no concerted control of the entire TO system.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed1977

Oxidation of corticosteroids to steroidal carboxylic acids by an enzyme preparation from hamster liver.

Enzyme activity which catalyzes the oxidation of 11-deoxycorticosterone to 21-oic acids accompanies the "detritiating" enzyme (isomerase) of hamster liver recently isolated by Martin, K. O., et al. ((1977) Biochemistry 16 (preceding paper in this issue)). The metabolites isolated were 20alpha- and 20beta-hydroxy-3-oxo-pregn-4-en-21-oic acid and 3,20-dioxo-pregn-4-en-21-oic acid. When 21-hydroxy[4-14C, 21-3H]pregn-4-en-3,20-dione was the substrate, about half of the tritium was retained in position 20 of the hydroxy acids. The system which catalyzes the conversion of the ketol side chain of corticosteroids to acid metabolites appears to be a cluster of closely related enzymes. As a result of these studies, we believe that the hamster liver enzyme preparation provides a useful model system for studies on the biosynthesis of acid metabolites of the corticosteroids in man.

Adrenal Cortex Hormones↗
PubMed1977

Studies in the biotransformation of cortisol to the cortoic acids in man. II. The central role of tetrahydrocortisol and tetrahydrocortisone as intermediates.

The possible role of THF and THE as intermediates in the biotransformation of cortisol to the cortoic acids was studied by giving 3H-THF + 14C-cortisol tracers and 3H-THE + 14C cortisol tracers to two subjects each, measuring the 3H/14C isotope ratios of the urinary cortoic acid metabolites and relating these ratios to the dose ratio. Isotope ratios substantially higher than the dose ratio indicate that the tetrahydro compound is a better precursor than cortisol, and isotope ratios that are essentially identical to that of urinary THF or THE, respectively, indicate that the tetrahydro compound may be an obligatory intermediate in the cortisol leads to cortoic acids pathway. The isotope ratio data in these studies clearly establish that THF was a preferential precurosor of the 11 beta-hydroxy cortoic acids (cortolic and beta-cortolic) and THE was a preferential precursor of the 11-ketone cortoic acids (cortolonic and beta-cortolonic). Furthermore, the data strongly suggest that THF and THE may be obligatory intermediates in cortoic acid formation.

Carboxylic Acids↗