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T Cronholm

Publications and source records attributed to T Cronholm.

At least 55 records · Page 3Linked to original sources
PubMed1984

Decrease in arachidonoyl-containing phosphatidylinositols in pancreas of rats fed an ethanol-containing diet.

The composition of the glycerophosphatides in pancreas and liver was studied in rats fed an ethanol-containing diet and in pair-fed controls. The fraction of arachidonoyl-containing phosphatidylinositols in pancreas was much lower in the former rats, also when the rats were starved for a final 24 hr period. This fraction was also lower in fed than in starved control rats. The effect was not observed after acute administration of ethanol. It is suggested that the decrease in arachidonoyl-containing phosphatidylinositols was due to chronic pancreatic hyperfunction in the ethanol-fed rats.

Animals↗
PubMed1984

Excretion of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 26-tetrol and corticosterone metabolites in rat bile. Studies on the role of alcohol dehydrogenase in steroid metabolism.

The monosulphate of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 26-tetrol was identified in bile of female and male rats. The excretion in the female rats decreased from 10-20 nmol/h directly after insertion of the bile cannula to very low values after 6 h. It then increased to reach a constant rate after 24 h that was slightly lower than during the first hour. Administration of 4-methylpyrazole or ethanol failed to change the rate of excretion. Thus there was no increase in the rate of excretion that might have resulted from an inhibited oxidation catalyzed by alcohol dehydrogenase (EC 1.1.1.1). Male rats were fed liquid ethanol-containing and control diets for 24 days prior to insertion of the bile cannula. The excretion during the first 3 h was 10-30 nmol/h in both groups, and chronic ethanol treatment did not change this rate. The effect of 4-methylpyrazole on the ratio between the excretion rates of the 3 beta- and 3 alpha-isomers of 3,11 beta, 21-trihydroxy-5 alpha-pregnan-20-one disulphate was measured by a gas chromatographic-mass spectrometric method. The absence of any significant change indicated that the 3 beta-hydroxysteroid dehydrogenase activity of alcohol dehydrogenase was of no significance in the metabolism of corticosterone.

Alcohol Dehydrogenase↗
PubMed1983

Origin of biliary phosphatidylcholines studied by coenzyme labelling with [1,1-2H2]ethanol.

The labelling of individual molecular species of phosphatidylcholines in bile and liver was measured in bile fistula rats given [1,1-2H2]ethanol immediately after the cannulation of the bile duct. Corresponding species in liver and bile were labelled to the same extent, the deuterium excess in the glycerol moiety (at C-2) of biliary molecules with rapid turnover possibly being slightly higher in the bile than in liver. The labelling of different positions and the half-life times of different molecular species were about the same as previously found 48 h after the cannulation. The only exception was the 1-stearoyl-2-linoleoyl species, which had a half-life time 5-7 times longer immediately after operation than after 48 h of biliary drainage. The results support our previous conclusion that the molecular species of phosphatidylcholines in liver and bile represent the same, or very similar, pool(s) of molecules.

Animals↗
PubMed1983

NAD+-dependent ethanol oxidation: redox effects and rate limitation.

Effects of ethanol on interconversion of cyclohexanol and cyclohexanone was studied in isolated hepatocytes. Oxidation and reduction catalyzed by alcohol dehydrogenase were markedly inhibited and stimulated, respectively. The changed ratio between the rates indicated that the ratio of NAD+ to NADH bound to alcohol dehydrogenase decreased several hundred times. This is much more than for the NAD+ system used by, e.g., lactate dehydrogenase, and deuterium from [1,1-2H2] ethanol was incorporated in cyclohexanol much more than in, e.g., lactate. These results indicate that the coenzyme bound to alcohol dehydrogenase is not equilibrated with free coenzyme. Thus, the dissociation of NADH might be rate-limiting for ethanol oxidation. Deuterium transfer from chiral [1-2H] ethanols and [2-2H] glycerol in hepatocytes indicated that cytosolic malate dehydrogenase and lactate dehydrogenase were not completely equilibrated, whereas there was no difference in the utilization of NADH formed at alcohol dehydrogenase and at glycerol-3-phosphate dehydrogenase. Fluxes in redox reactions during ethanol oxidation may be too high for equilibration of cytosolic dehydrogenases.

Animals↗
PubMed1982

Effects of ethanol metabolism on oxidoreduction and intermolecular hydrogen transfer at C-17 in steroid 3-sulphates in vivo.

Steroid sulphates were infused intravenously in female rats, and metabolites were isolated from bile. Infused 3 beta-hydroxy-5 alpha-androstan-17-one 3-sulphate was excreted together with 5 alpha-androstane-3 beta,17 beta-diol disulphate, which formed a large part after ethanol administration. Results from infusions of the 3-sulphates of 5 alpha-[17 alpha-2H]androstane-2 beta,17 beta-diol and 3 beta-hydroxy-5 alpha-[2,2,4,4-2H4]androstan-17-one indicated that ethanol decreased the extent of transfer of the 17 alpha-deuterium and increased the reduction of 17-oxosteroid without affecting the oxidation of 17 beta-hydroxysteroid. Ethanol metabolism decreased the deuterium transfer from [17 alpha-2H]estradiol 3-sulphate to C-17 of 3 beta-hydroxy-5 alpha-androstan-17-one 3-sulphate. The results indicate that NADH from ethanol metabolism increased the concentration of oxidoreductase-NADH complex without affecting the corresponding complex with NAD+. The effects of ethanol on steroid reduction were dependent on the initial redox state of the enzyme-coenzyme complex. This redox state was modified by substrates for the enzyme, indicating slow dissociation of the complex. Thus, ethanol metabolism may interfere with the interactions between steroid oxidoreductions.

Androstane-3,17-diol↗
PubMed1980

Biosynthesis of 5 alpha- and 5 beta-cholanoic acid derivatives during metabolism of [1,1-2H]- and [2,2,2-2H]ethanol in the rat.

Female bile fistula rats were given [1,1-2H]ethanol in a single dose or [2,2,2-2H]ethanol repeatedly for 24 h and incorporation of deuterium into the following bile acids was determined: taurine conjugates of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5(alpha and beta)-cholanoic, 3 alpha, 7 alpha-dihydroxy-5(alpha and beta)-cholanoic and 3 alpha, 6 beta, 7 alpha-trihydroxy-5 beta-cholanoic acids; sulphates of 3(alpha and beta), 7 alpha, 12 alpha-trihydroxy-5 alpha-cholanoic, and 3(alpha and beta), 7 alpha-dihydroxy-5 alpha-cholanoic acids. The kinetics of deuterium incorporation from [2,2,2-2H]ethanol was the same for all bile acids indicating that they were formed from a single pool of cholesterol. The labelling pattern of bile acids formed during metabolism of [1,1-2H]-ethanol indicated that the hydrogen at C-5 was labelled in all bile acids. Taken together with previous results this indicates that 3-oxo-4-cholenoic acid is not an intermediate in the formation of allo bile acids. The results support the view that formation of allo bile acids via a mitochondrial pathway is of little importance in the bile fistula rat.

Animals↗
PubMed1979

Exchange of methyl hydrogens in ethanol during incorporation in bile acids in vivo.

[2,2,2-2H]Ethanol was administered continuously to bile fistula rats for 72 h, with or without (--)-hydroxycitrate. The deuterium labelling of biliary bile acids was determined by GC-MS and 13C NMR. Difference spectra between 2H,1H- and 1H-decoupled 13C NMR spectra showed the presence of partly deuterated methyl and methylene groups in methyl cholate, indicating exchange of deuterium in [2,2,2-2H]ethanol for protium prior to or during incorporation of acetate into the bile acid. The extent of exchange was 20--30% as calculated from the isotopic composition of a fragment ion containing one methyl and one methylene group derived from C-2 of acetate. The exchange was unaffected by (--)-hydroxycitrate, indicating that it was not due to reversible incorporation of deuterated acetate into citrate. About 60% of the acetyl-CoA serving as precursor of cholic and chenodeoxycholic acids were derived from ethanol. This value was not changed by administration of (--)-hydroxycitrate. The half-life time of cholesterol molecules acting as precursors of both bile acids was about 50 h in the presence of (--)-hydroxycitrate, which is about the same as previously found in the absence of the inhibitor.

Acetyl Coenzyme A↗
PubMed1977

Incorporation of the 1-pro-R and the 1-pro-S hydrogen atoms of ethanol into steroids and phosphatidylcholines in vivo.

The transfer of deuterium from chiral 1-monodeuteroethanols to various metabolites formed in the liver was studied in order to investigate the coupling of metabolic reductions to the alcohol dehydrogenase and the aldehyde dehydrogenase reactions. The ethanols were administered to female bile fistula rats for 10 h. The hydrogen at C-2 in the glycerol moiety of newly formed phosphatidylcholine molecules in bile, liver and plasma was derived to 22-25% from the 1-pro-R position and to 5-6% from the 1-pro-S position in the ethanol. sn-Glycerol 3-phosphate isolated from liver had a lower deuterium content at C-2. The ratio between the contributions from the two positions in ethanol to C-2 of free sn-glycerol 3-phosphate was the same as in the phosphatidylcholines. This indicates that the higher degree of labelling of this position in phosphatidylcholines is not due to a specific coupling between alcohol dehydrogenase and the formation of a phosphatidylcholine precursor. Cholesterol and chenodeoxycholic acid in bile became increasingly labelled, and the ratio between the incorporations from the 1-pro-S and the 1-pro-R positions of ethanol was about 0.37 in cholesterol and 0.46 in chenodeoxycholic acid. Thus, these NADPH-dependent reactions utilized hydrogen from the 1-pro-S position to a larger extent than NADH-dependent reactions.

Animals↗
PubMed1976

Transfer of the 1-pro-R and the 1-pro-S hydrogen atoms of ethanol in metabolic reductions in vivo.

The transfer of deuterium from [1 R-2H]ethanol and [1 S-2H]-ethanol to reduced metabolites of administered compounds was measured in female rats provided with bile fistulas. Administered cyclohexanone was reduced to cyclohexanol, and in this reduction hydrogen was transferred only from the 1-pro-R position of the ethanol. The deuterium content in the cyclohexanol was about 67% of that in the ethanol. In the reduction of the 17-oxo group in 3beta-hydroxy-5alpha-androstan-17-one, hydrogen was transferred both from the 1-pro-R position and the 1-pro-S position, resulting in degrees of labelling that were about 25% and 2%, respectively, of those in the specific positions of the ethanols. The 1-pro-R and 1-pro-S positions of ethanol contributed about 9% and 5%, respectively, of the 3beta hydrogen in lithocholic acid formed from 3-oxo-5beta-cholanoic acid. The results indicate that alcohol dehydrogenase and aldehyde dehydrogenase do not share a common pool of NAD, and that NADH formed during acetaldehyde oxidation is utilized for reductions in the cytosol to a smaller extent than the NADH formed in the alcohol dehydrogenase reaction. This result supports the concept that aldehyde oxidation is mainly an intramitochondrial process. The relatively extensive utilization of the 1-pro-S hydrogen of ethanol in the reduction of 3-oxo-5beta-cholanoic acid, that is probably NADPH-dependent, indicates that cytosolic NADPH may be produced from malate or isocitrate formed intramitochondrially.

Alcohol Oxidoreductases↗
PubMed1975

Deuterium transfer from [1,1-2-H] ethanol during metabolism of bile acids and cyclohexanone in the isolated perfused rat liver.

Deuterium transfer from [1,1-2-H]ethanol (95 atoms % excess) to reducible substrates was studied in the isolated perfused rat liver. The dueterium excess in cyclohexanol formed from cyclohexanone was somewhat lower (49 atoms%) than found under conditions in vivo, and this was also true of the deuterium excess in lithocholic acid formed from 3-oxo-5beta-cholanoic acid. These results may reflect a slower rate of ethanol oxidation in the isolated organ than in vivo. Cycloserine decreased the dueterium transfer to both substrates, whereas addition of lactate and malate resulted in an increased deuterium excess in cyclohexanol and a decreased deuterium excess in lithocholic acid. Addition of heavy water to the perfusion fluid resulted in labelling at C-3 of lithocholic acid formed from 3-oxo-5beta-cholanoic acid, and at C-3, C-4 and C-5 of 3alpha-hydroxy-5alpha-cholanoic acid formed from 3-oxo-4-cholenoic acid. The deuterium excess of hydrogens derived from NADPH (at C-3 and C-5) was approximately the same as that of hydrogen derived directly from water (at C-4). Thus, the hydrogen of NADPH is extensively exchanged with protons of water, which explains the dilution of deuterium with protium during the transfer from [1,1-2-H]ethanol via NADPH to the bile acids. The labelling at C-5 in the reduction of the 4,5-double bond indicates that different pools of NADPH are used for reduction of this double bond and the 3-oxo group, since in a previous study it was shown that deuterium is transferred from [1,1-2-H]ethanol only in the latter reaction.

Animals↗
PubMed1975

Steroid oxidoreductase activity of alcohol dehydrogenases from horse, rat, and human liver.

Alcohol dehydrogenase from horse (isoenzyme SS and ES, but not EE), rat and human liver were found to catalyze the NAD-dependent oxidation of 3beta-hydroxy groups in 5alpha- and 5beta-steroids of the C19, C21, and C24 series. The enzymes from horse and rat liver were more active on 5beta-than on 5alpha-steroids. This difference was most marked with the enzyme from rat liver, especially with 3beta-hydroxyandrostan-17-ones and 3beta-hydroxypregnan-20-ones as substrates. The Km of isoenzyme ES from horse liver was lower for 3beta-hydroxy-5alpha-cholanoic acid (0.4 muM) than for 3beta-hydroxy-5beta-cholanoic acid (0.9 muM). 3alpha-Hydroxysteroids were not substrates for the enzymes from horse and rat liver. Human liver alcohol dehydrogenase had low affinity for 3beta-hydroxy-5alpha (and 5beta)-cholanoic acids, but oxidation could be clearly demonstrated by gas chromatographic analysis of the products.

Alcohol Oxidoreductases↗