Choline—Chemistry and Signlficance as a Dietary Factor

Best, C. H.; Lucas, Christophe

doi:10.1016/s0083-6729(08)60251-4

Cited by 57 publications

(4 citation statements)

References 193 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dietary deficiency of choline in rodents causes development of hepatocarcinomas in the absence of any known carcinogen (23,24). Therefore, choline is a significant dietary factor (25). Normally, the body conserves choline very well (22).…”

Section: Resultsmentioning

confidence: 99%

Application of Metabonomics in a Compound Ranking Study in Early Drug Development Revealing Drug-Induced Excretion of Choline into Urine

Dieterle

Schlotterbeck

Ross

et al. 2006

Chem. Res. Toxicol.

View full text Add to dashboard Cite

Selecting drug candidates based on toxicity is an important step in early drug development. In this case study, it is shown how metabonomics is applied to a ranking study, in which drug candidates with equal pharmacological activities are selected based on least toxic side effects. The metabonomic analyses were carried out on an animal study that followed an established protocol for pilot toxicology/ranking studies in rats, however, not specifically modified for a metabonomic assessment. It is shown how conditions not specificially adopted for metabonomics investigations can significantly influence the metabolic profiles recorded by NMR. Furthermore, it is shown how the multivariate analysis of the NMR spectra identified an extreme excretion of an endogenous metabolite into urine induced by two out of the five drug candidates. The subsequent structure elucidation by two-dimensional NMR experiments and a subsequent validation by spiking experiments identified the metabolite as choline. The discussion of the mechanistic background for the excretion of choline, which is usually well-conserved in the body, results in two hypotheses of either a massive degradation of cell membranes or an inhibition of the choline oxidation. Although the validation of these hypotheses needs a follow-up study, the finding of a increased excretion of the important metabolite choline warrants exclusion of these two compounds as viable drug candidates from a metabonomics point of view.

show abstract

Section: Resultsmentioning

confidence: 99%

Application of Metabonomics in a Compound Ranking Study in Early Drug Development Revealing Drug-Induced Excretion of Choline into Urine

Dieterle

Schlotterbeck

Ross

et al. 2006

Chem. Res. Toxicol.

View full text Add to dashboard Cite

show abstract

“…It might be inserted here that previous work on the effect of choline on lipids in blood or serum seems to have been confined to the effect of cholesterole mia in rabbits. Choline did not reduce the hypercholesterolemia of cholesterol fed rabbits (81).…”

Section: Factors Affecting Blood and Tissue Fatsmentioning

confidence: 79%

“…Luecke & Pearson (108) found that after choline deficiency in four mature rats the free choline but not the total choline diminished per gram of rat kidney tissue. Since the review of Griffith (122) further com parisons of the effects of various lipotropic agents on liver and kidney tissue have been made (81,91,99).…”

Section: Factors Affecting Blood and Tissue Fatsmentioning

confidence: 99%

Fat Metabolism

Gildea¹,

Man²

1945

Annu. Rev. Biochem.

View full text Add to dashboard Cite

This review covers some aspects of fat metabolism which have not been discussed in detail in previous years. It has been difficult to ob tain foreign literature and therefore the review is incomplete. NERVOUS SYSTEM AND FAT METABOLISMRelation of the hypothalamus to fat metabolism.-Since 1940 when the symposium on the hypothalamus was published by the Association for Research in Nervous and Mental Diseases (1), many groups of investigators have made systematic attacks on the problem of hypo thalamic regulation of metabolism including that of fat. Hetherington & Ranson (2, 3, 4) have demonstrated conclusively in rats that care fully placed bilateral lesions in the ventromedial nuclei of the hypothal amus (injury to pituitary was avoided) produced promptly increase of appetite and subsequently extreme obesity. Removal of the pituitary provoked no obesity, and also did not prevent development of obesity following hypothalamic lesions. Even when sufficient time after hypo physectomy, eleven weeks, was allowed to elapse for atrophy of thy roid, adrenals, and gonads to develop, subsequent hypothalamic lesions were still followed by hyperphagia and obesity. These results have been confirmed in the monkey by Brooks, Lambert & Bard (5), in the dog by Heinbecker et at. (6) , and in the cat by Wheatley (7). Hetherington (4) has tried, in an extensive series of experiments, to localize the lesions which consistently result in obesity. He con cluded that cell groups of basal forebrain rostral to the ventromedial hypothalamic nucleus made little if any contribution to regulation of fat metabolism. Destruction of the ventromedial hypothalamic nucleus or its descending fibers in the brain stem was required to produce hyperphagia and obesity.That diffuse injuries to brain may disturb fat metabolism has been suggested by the effects of insufflation of air into ventricles of the dog. Schrade (8) observed that three to four hours after air injection the total blood fats were reduced in amount. Phospholipids, cholesterol, and neutral fats all decreased in concentration. The change in cho-333 Annu. Rev. Biochem. 1945.14:333-356. Downloaded from www.annualreviews.org by Massachusetts Institute of Technology (MIT) on 11/05/14. For personal use only. Quick links to online content Further ANNUAL REVIEWS

show abstract

“…On the basis of the evidence now at hand, the nature of the interrelationship of adenine and the other two substances cannot be elucidated, although it is obvious that it cannot be simply competitive antagonism for a single enzyme. However, the similarity in behavior of both methionine and choline does appear significant in that both are known to be involved in phospholipid metabolism (Best and Lucas, 1943;Du Vigneaud et al, 1944).…”

Section: Discussionmentioning

confidence: 99%

Differences in Response of a Virulent Strain of the Tubercle Bacillus and Its Avirulent Variant to Metabolites and Their Genetic Significance

Marshak

1951

J Bacteriol

View full text Add to dashboard Cite

When colonies of virulent tubercle bacilli were maintained on solid egg media, Steenken (1935) found that eventually lysis occurred and new colonies of bacteria resistant to the lytic process appeared which proved to be avirulent. The phenomenon was observed in several human strains and in bovine strains as well (Steenken, 1938). Similar results were obtained when colonies from single cell cultures were grown to the point of lysis, indicating that the resistant colonies were not merely the result of selection of pre-existing resistant cells (Steenken, 1938). The distinguishing characteristics of the virulent and avirulent strains were maintained indefinitely on subculture, indicating that the virulent and avirulent strains differed genetically. Because of its long history (Steenken and Gardner, 1946) the strain H37Rv and its avirulent variant H37Ra were selected for investigation of the possible metabolic and genetic differences between the two strains. The results to be reported here show that the virulent and avirulent forms differ in their response to 16 different metabolites. The frequency of appearance of avirulent colonies (Steenken, 1938) suggests a single gene mutation as the basis for the difference between H37Ra and H37Rv. However, difficulty is encountered in reconciling the finding of a multiplicity of differences in response to metabolites in the two strains, with a single gene mutation, if the hypothesis that each enzyme is controlled by a single gene is accepted. Methods. In a liquid medium, the H37 strain of tubercle bacillus will synthesize all the materials it requires for growth from glucose as the sole carbon source and ammonium chloride as the source of nitrogen (Schaefer, Marshak, and Burkhart, 1949). The medium was NH4Cl-1.0 g, Na2HPO4-12H20-6.5 g, KH2PO4-1.0 g, MgSO4 7H20-0.02 g, CaCl2-0.0005 g, and FeCl3-6H20-0.0005 g dissolved in 1 liter of distilled water that also contained sorbitan monooleate ("tween 80") in a concentration of 0.02 per cent. After being autoclaved, sterile 50 per cent glucose was added to a final concentration of 0.1 per cent and 5 per cent sterile bovine serum albumin2 to a concentration of 0.01 per cent. Cultures of tubercle bacilli in 6 ml of Dubos medium (Davis and Dubos, 1947) grown in slanted screw-cap tubes, 2 cm by 13 cm, for 9 to 10 days were centrifuged, and the cells were washed twice in the foregoing medium and then resus

show abstract

Choline—Chemistry and Signlficance as a Dietary Factor

Cited by 57 publications

References 193 publications

Application of Metabonomics in a Compound Ranking Study in Early Drug Development Revealing Drug-Induced Excretion of Choline into Urine

Application of Metabonomics in a Compound Ranking Study in Early Drug Development Revealing Drug-Induced Excretion of Choline into Urine

Fat Metabolism

Differences in Response of a Virulent Strain of the Tubercle Bacillus and Its Avirulent Variant to Metabolites and Their Genetic Significance

Contact Info

Product

Resources

About