scholarly journals The incorporation of a hydrogen atom at C-15 of cholesterol biosynthesized from squalene

1969 ◽  
Vol 114 (4) ◽  
pp. 801-806 ◽  
Author(s):  
M Akhtar ◽  
A. D. Rahimtula ◽  
D. C. Wilton
Keyword(s):  
Hydrogen Atom ◽  
Cholesterol Biosynthesis ◽  
Tritiated Water ◽  
Total Radioactivity ◽  
Chemical Degradation

Cholesterol is biosynthesized from squalene in the presence of tritiated water. Chemical degradation reveals that a considerable percentage of the total radioactivity is present at C-15. This result confirms the previous observations on the involvement of a C-15 hydrogen atom in cholesterol biosynthesis.

scholarly journals The role of a cholesta-8,14-dien-3β-ol system in cholesterol biosynthesis

1969 ◽  
Vol 111 (5) ◽  
pp. 757-761 ◽  
Author(s):  
M. Akhtar ◽  
I. A. Watkinson ◽  
A. D. Rahimtula ◽  
D. C. Wilton ◽  
K. A. Munday
Keyword(s):  
Hydrogen Atom ◽  
Cholesterol Biosynthesis ◽  
Tritiated Water ◽  
Mevalonic Acid ◽  
Hydrogen Atoms ◽  
Steroid Biosynthesis ◽  
Methyl Group

The biosynthesis of cholesterol from squalene and tritiated water is described. Degradation of the cholesterol indicated that C-15 may be involved in cholesterol biosynthesis. In accordance with this view it is shown that in the conversion of [2RS−3H2]mevalonic acid into cholesterol one of the hydrogen atoms at C-15 is removed. A mechanism for the removal of the 14α-methyl group in steroid biosynthesis that involves the labilization of a C-15 hydrogen atom is outlined. In accordance with the requirement of this scheme it is shown that 4,4′-dimethyl-cholesta-8,14-dien-3β-ol is converted into cholesterol.

scholarly journals The enzymic degradation of l-serine O-sulphate. Mechanism of the reaction

1972 ◽  
Vol 128 (1) ◽  
pp. 41-46 ◽  
Author(s):  
N. Tudball ◽  
P. Thomas
Keyword(s):  
Hydrogen Atom ◽  
Carbon Atom ◽  
Rose Bengal ◽  
Incubation Medium ◽  
Tritiated Water ◽  
Competitive Inhibitor ◽  
Histidine Residues ◽  
Photo Oxidation ◽  
Rapid Inactivation ◽  
Mechanism Of The Reaction

1. During the enzyme-catalysed degradation of l-serine O-sulphate no exchange occurs between the hydrogen atom attached to the α-carbon atom of the substrate and the tritiated water of the incubation medium. 2. The participation of an intermediate carbanion has been demonstrated in the degradation by performing the reaction in the presence of tetranitromethane. 3. Photo-oxidation of the enzyme in the presence of Rose Bengal led to a rapid inactivation of enzyme with the concomitant loss of four histidine residues/molecule. 4. Rose Bengal was also a non-competitive inhibitor of the enzyme.

scholarly journals Incorporation of [2−14C,(5R)-5−3H1]mevalonic acid into cholesterol by a rat liver homogenate and into β-sitosterol and 28-isofucosterol by Larix decidua leaves

1969 ◽  
Vol 114 (4) ◽  
pp. 885-892 ◽  
Author(s):  
L J Goad ◽  
G. F. Gibbons ◽  
Loretta M. Bolger ◽  
H H Rees ◽  
T W Goodwin
Keyword(s):  
Double Bond ◽  
Hydrogen Atom ◽  
Rat Liver ◽  
Cholesterol Biosynthesis ◽  
Liver Homogenate ◽  
Mevalonic Acid ◽  
Atomic Ratio ◽  
Larix Decidua ◽  
Tritium Atom

1. Incubation of a rat liver homogenate with 3R-[2−14C,(5R)-5−3H1]mevalonic acid gave cholesterol with 3H/14C atomic ratio 6:5. 2. Conversion of the labelled cholesterol into 3β-acetoxy-6-nitrocholest-5-ene or cholest-4-ene-3,6-dione resulted in the loss of one tritium atom from C-6. 3. These results show that during cholesterol biosynthesis the 6α-hydrogen atom of a precursor sterol is eliminated during formation of the C-5–C-6 double bond. 4. Incorporation of 3R-[2−14C,(5R)-5−3H1]mevalonic acid into the sterols of larch (Larix decidua) leaves gave labelled cycloartenol and β-sitosterol with 3H/14C atomic ratios 6:6 and 6:5 respectively. 5. One tritium atom was lost from C-6 on conversion of the labelled β-sitosterol into either 3β-acetoxy-6-nitrostigmast-5-ene or stigmast-4-ene-3,6-dione, demonstrating that formation of the C-5–C-6 double bond of phytosterols also involves the elimination of the 6α-hydrogen atom of a precursor sterol. 6. The 3R-[2−14C,(5R)-5−3H1]mevalonic acid was also incorporated by larch (L. decidua) leaves into a sterol that co-chromatographed with 28-isofucosterol. Confirmation that the radioactivity was associated with 28-isofucosterol was obtained by co-crystallization with carrier 28-isofucosterol and ozonolysis of the acetate to give radioactively labelled 24-oxocholesteryl acetate. 7. The significance of these results to phytosterol biosynthesis is discussed.

scholarly journals Studies of cholesterol biosynthesis. 1. A new chemical degradation of cholesterol

1953 ◽  
Vol 54 (4) ◽  
pp. 590-597 ◽  
Author(s):  
J. W. Cornforth ◽  
G. D. Hunter ◽  
G. Popják
Keyword(s):  
Cholesterol Biosynthesis ◽  
Chemical Degradation

scholarly journals The reversibility of the Δ8-cholestenol–Δ7-cholestenol isomerase reaction in cholesterol biosynthesis

1969 ◽  
Vol 114 (1) ◽  
pp. 71-73 ◽  
Author(s):  
D. C. Wilton ◽  
A. D. Rahimtula ◽  
M Akhtar
Keyword(s):  
Cholesterol Biosynthesis ◽  
Tritiated Water

The incubation of Δ7-cholestenol with a 10000g supernatant or 105000g microsomes in the presence of tritiated water is studied. The reisolated Δ7-cholestenol contained up to 0·67g.atom of tritium/mole. This result can best be explained by assuming the reversibility of the reaction Δ8-cholestenol ⇌ Δ7-cholestenol.

scholarly journals Incorporation of dl-[2−14C]ornithine and dl-[5−14C]arginine in milk constituents by the isolated lactating sheep udder

1968 ◽  
Vol 106 (3) ◽  
pp. 719-724 ◽  
Author(s):  
R. Verbeke ◽  
G. Peeters ◽  
Anne Marie Massart-Leën ◽  
G. Cocquyt
Keyword(s):  
Carbon Dioxide ◽  
Amino Acids ◽  
Glutamic Acid ◽  
Mammary Glands ◽  
Total Radioactivity ◽  
Chemical Degradation ◽  
Mammary Tissue ◽  
Specific Activities ◽  
Plasma Arginine

1. Lactating mammary glands of sheep were perfused for several hours in the presence of dl-[2−14C]ornithine or dl-[5−14C]arginine and received adequate quantities of acetate, glucose and amino acids. 2. In the [14C]ornithine experiment 1·4% of the casein and 1% of the expired carbon dioxide came from added ornithine; 96% of the total radioactivity in casein was recovered in proline; 13% of the proline of casein originated from plasma ornithine. 3. In this experiment the results of chemical degradation of proline of casein as well as relative specific activities in the isolated products are consistent with the view that ornithine is metabolized, by way of glutamic γ-semialdehyde, to proline or glutamic acid. 4. In the [14C]arginine experiments 3% of the casein and 1% of the expired carbon dioxide came from arginine; 84% of the arginine and 9% of the proline of casein originated from plasma arginine. 5. In these experiments the relative specific activities of arginine, ornithine and proline in plasma are in agreement with the view that arginine is metabolized by way of ornithine to proline. The conversion of arginine into ornithine is probably catalysed by arginase, so that arginase in mammary tissue may be involved in the process of milk synthesis.

scholarly journals The formation and reduction of the 14,15-double bond in cholesterol biosynthesis

1971 ◽  
Vol 121 (1) ◽  
pp. 131-137 ◽  
Author(s):  
I. A. Watkinson ◽  
D. C. Wilton ◽  
K. A. Munday ◽  
M. Akhtar
Keyword(s):  
Double Bond ◽  
Hydrogen Atom ◽  
Rat Liver ◽  
Related Compound ◽  
Cholesterol Biosynthesis ◽  
Liver Homogenate ◽  
Compound Iiia ◽  
Sterol Biosynthesis ◽  
Methyl Group

It was shown that 100μg quantities of 4,4′-dimethyl[2-3H2]cholesta-8,14-dien-3β-ol (IIIa), tritiated cholesta-8,14-dien-3β-ol, 4,4′-dimethyl[2-3H2]cholesta-7,14-dien-3β-ol, dihydro[2-3H2]lanosterol and [24-3H]lanosterol were converted by a 10000g supernatant of rat liver homogenate into cholesterol in 17%, 54%, 6%, 9.5% and 24% yields respectively. From an incubation of dihydro[3α-3H]lanosterol with a rat liver homogenate in the presence of a trap up to 38% of the radioactivity was found to be associated with a fraction that was unambiguously shown to be 4,4′-dimethylcholesta-8,14-dien-3β-ol. Another related compound, 4,4′-dimethylcholesta-7,14-dien-3β-ol was also shown to be equally effective in its ability to trap compound (IIIa) from an incubation of dihydro[3α-3H]lanosterol. The mechanism of the further conversion of the compound (IIIa) into cholesterol occurred by the reduction of the 14,15-double bond and involved the addition of a hydrogen atom from the medium to C-15 and another from the 4-position of NADPH to C-14. Two possible mechanisms for the removal of the 14α-methyl group in sterol biosynthesis are discussed.

scholarly journals The biological conversion of 7-dehydrocholesterol into cholesterol and comments on the reduction of double bonds

1968 ◽  
Vol 106 (4) ◽  
pp. 803-810 ◽  
Author(s):  
D. C. Wilton ◽  
K A Munday ◽  
S. J. M. Skinner ◽  
M Akhtar
Keyword(s):  
Hydrogen Atom ◽  
Rat Liver ◽  
Enzyme System ◽  
Tritiated Water ◽  
Liver Homogenate ◽  
Double Bonds ◽  
Hydrogen Atoms ◽  
Biological Conversion ◽  
Microsomal Pellet

It is shown that the 7-dehydrocholesterol reductase-catalysed conversion of 7-dehydrocholesterol into cholesterol (II), with a 105000g microsomal pellet of rat liver in the presence of [4−3H2]NADPH, results in the transfer of radioactivity to the 7α-position of cholesterol. When the conversion is carried out in the presence of tritiated water the label is introduced exclusively at the 8β-position. However, when the conversion of 7-dehydrocholesterol into cholesterol is performed with a 500g supernatant of rat liver homogenate the radioactivity is incorporated at both the 7α- and the 8β-position. Evidence is provided for the presence of an enzyme system in the 500g supernatant that catalyses an equilibration of hydrogen atoms between those at the 4-position of NADPH and those of water. The work with stereospecifically labelled cofactors shows that both the equilibrating system and the 7-dehydrocholesterol reductase utilize the 4B-hydrogen atom of NADPH. In the light of these results a mechanism for the reduction of carbon–carbon double bonds is discussed.

MODEL STUDY OF FACTORS INFLUENCING STEADY STATE CLEARANCE FOR LIPOPHILIC TOXICANTS IN AQUATIC MICROCOSMS

2001 ◽  
Vol 09 (02) ◽  
pp. 123-143 ◽  
Author(s):  
ANDRÉS VENTURINO ◽  
MARÍA GABRIELA ROVEDATTI ◽  
LIDIA GAUNA ◽  
MIRIAM LOEWY ◽  
ANA MARÍA PECHEN DE D'ANGELO
Keyword(s):  
Steady State ◽  
Organophosphorus Pesticide ◽  
Simulated Data ◽  
Total Radioactivity ◽  
Chemical Degradation ◽  
Practical Result ◽  
Model Study ◽  
Apparent Clearance ◽  
Linear Differential ◽  
Physical And Chemical

We have studied the distribution and bioelimination of the organophosphorus pesticide parathion in a native microcosm consisting of water, sediment, bivalves and aquatic plants. A common apparent clearance constant for biotic and abiotic components was suggested from the analysis of parathion accumulation and degradation. In this work we developed a global model explaining the toxicokinetics of a lipophilic compound and particurlarly the common steady state degradation in an aquatic microcosm, using a set of linear differential equations. We simulated the distribution and degradation of the compound in the microcosm, and fitted single-compartment equation models to data, estimating the apparent sorption and elimination constants. We verified the existence of a common apparent degradation constant for all the compartments. We infer from the mathematical expressions and corroborate from the simulated data that the apparent degradation constant is equal to the sum of the metabolization rates at each biotic compartment multiplied by the compound mass ratios established at steady state between the biotic and the abiotic compartments. Product kinetics simulation showed that steady state might also be achieved in the different compartments, with the same apparent constant as that obtained for toxicant clearance. As a practical result, the total radioactivity in water would serve to calculate the global clearance constant in a simple experimental way if a radiotracer is used. Physical and chemical degradation and chemical loss due to volatilization and CO 2 diffusion were analyzed in the microcosm model. The assessments of the cases where these factors affect the clearance process as well as the implications emerged are discussed.

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