Studies of the excretion of cholesterol and its metabolites

Mitchell, William Derek (1969) Studies of the excretion of cholesterol and its metabolites. PhD thesis, University of Glasgow.

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This thesis describes work on the development of new techniques of faecal neutral steroid and bile acid analysis and the application of these techniques to a variety of clinical circumstances in which the metabolism of cholesterol, and the output of faecal steroids might be altered. The thesis is in four main parts, 1. A consideration from an historical standpoint of cholesterol metabolism and its regulation; in particular, the reduction of serum cholesterol levels by three groups of compounds; a) Inhibitors of cholesterol biosynthesis either at an early stage in the biosynthetic pathway or at a stage after the cyclisation of squalene. b) Compounds which cause increased excretion of faecal bile acids and/or faecal neutral steroids. c) Compounds which act by impairing cholesterol absorption. 2. A review of the application of thin layer chromatography (TLC) to lipid analysis. In this section the use of silver nitrate impregnated TLC, reversed phase TLC and derivatives in the separation of structurally similar compounds are discussed together with the application of TLC to quantitative analysis of faecal neutral steroids and bile acids. 3. A detailed consideration of the way in which TLC and other methods have been modified for use in the present study. The extraction of neutral steroids and bile acids from faeces is described together with methods for their qualitative and quantitative analysis . A technique for estimating biliary bile acids is also described. 4. The final section is concerned with the application of quantitative techniques of neutral steroid and bile acid analysis to four problems. a). The effect of oral taurine on serum cholesterol and biliary bile acid conjugation was studied in three subjects. The results suggest that although the proportion of bile acids conjugated with taurine in human bile can be readily increased by feeding taurine this has no effect on serum cholesterol concentrations. b). The mechanism by which clofibrate reduces serum cholesterol in patients with hypercholesterolaemia was investigated by three approaches. 1). The effect of clofibrate on the pattern of biliary bile acids in five subjects with hypercholesterolaemia. 2). The effect of clofibrate on faecal neutral steroids and bile acids in twenty one subjects. 3). A comparison of the effect of clofibrate and L-thyroxine on serum and faecal lipids in four hypothyroid patients. Clofibrate did not appear to alter the conjugation ratio or the pattern of biliary bile acids in the five subjects studied. The results of the comparative study with L-thyroxine suggest that the mechanism of action of clofibrate is quite different to that of L-thyroxine in lowering serum lipids. Studies of faecal bile acids and neutral steroids in the 21 subjects strongly suggest that the reduction of serum cholesterol by clofibrate is not produced by an increased excretion of cholesterol or its metabolites in faeces. Inhibition of hepatic synthesis of cholesterol seems a more likely explanation. c). The effect of increased oral calcium on faecal neutral steroids and bile acids was studied in six subjects. Although calcium markedly increased faecal bile acid excretion there was no reduction in serum cholesterol concentration. d). The final problem studied was the effect of dietary cholesterol on serum and faecal lipids in a single subject. The results of this experiment suggest that there is a negative feedback mechanism in which the level of dietary cholesterol controls the hepatic synthesis of cholesterol.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Advisers: G M Wilson; E Wayne
Keywords: Medicine
Date of Award: 1969
Depositing User: Enlighten Team
Unique ID: glathesis:1969-72738
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jun 2019 11:06
Last Modified: 11 Jun 2019 11:06

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