The cyclopropene fatty acids, sterculic and malvalic, occur naturally in a major food lipid, cottonseed oil, and have been implicated in several physiological disorders. Rainbow trout in this study were fed semipurified diets containing 200 or 300 ppm methyl sterculate, and the effects on hepatic lipid and glycogen levels, lipid incorporation of radioactive phosphate and fatty acids, and mitochondrial energy production were investigated. Chronic ingestion of methyl sterculate caused numerous histological changes and some necrosis in the liver. Glycogen accumulated in irregular pockets, but the level in whole liver was not increased over controls. Hepatic lipid accumulation was noted after several weeks, reaching a level six times that of controls after six months. Liver weight of the sterculate-fed fish decreased in proportion to body weight during the first three weeks on the sterculate diet, but after three months became significantly greater than controls. Ingestion of 200 ppm methyl sterculate for two weeks by trout caused reduced incorporation of both phosphate and fatty acids into phospholipids. The major reductions were found in minor fractions. Label incorporation into cardiolipin, important for mitochondrial function, was reduced ten-fold by the dietary sterculate. Incorporation into a minor unknown phospholipid which constituted less than 1% of total phospholipids was reduced as much as 135-fold in the mitochondrial fraction. Incorporation of 1-¹⁴C-oleate into diglycerides was also inhibited. The major changes caused by methyl sterculate appear to occur in mitochondria. Neither the level of cytochrome P⁴⁵⁰ nor the activity of NADPH neotetrazolium reductase, both of which occur in the endoplasmic reticulum, was altered. P/0 ratios and the ability to oxidize oleic acid to CO₂ were curtailed after only two weeks on a diet containing methyl sterculate. / Graduation date: 1974

It has been suggested that membrane characteristics associated with carcinomas could be related to an altered molecular structure of lipids in the plasma membrane. The microsomal fraction, mitochondria and soluble fractions of the cell are major sites of de novo synthesis and elongation of fatty acids. It was the purpose of this study to compare the utilization of AcSCoA in the biosynthetic pathway for saturated fatty acids in tumor and normal tissue, and discern if any deviations in the initial steps of the pathway were responsible forr the observed differences in the plasma membrane of tumors. Labeled 14C-AcSCoA was incorporated into saturated fatty acids in both adenocarcinomas and normal mammary tissue. The distribution and degree of incorporation of labeled 14C-AcSCoA was hoped to demonstrate any deviations in the pathway.Crude supernate, microsomal fraction, mitochondria and soluble fractions were isolated from mammary adenocarcinomas and from normal mammary tissue of Strain A female mice by differential centrifugation. The activity of fatty acid synthetase in the soluble fraction was determined. The crude supernate, the soluble fraction, the mitochondria + soluble fraction and the microsomal fraction + soluble fraction of both the adenocarcinoma and normal mammary tissue were incubated with labeled 14C-AcSCoA, Ma1SCoA and all necessary cofactors. The now labeled fatty acids were extracted from these incubation mixtures. The total percent of incorporated labeled 14C-AcSCoA in each fraction was determined. The percent of incorporation of label into individual saturated fatty acids in each fraction was determined by gas liquid chromatography and liquid scintillation counting. Carrier mixtures of known fatty acids were added to the samples used for GLC analysis to confirm the identity of the labeled fatty acids.Results of this study show that the percent of labeled i4C-AcSCoA incorporated into the various saturated fatty acids was similar in tumor and normal tissue. However, the total uptake of AcSCoA was nearly twice as great in normal tissue. The activity of fatty acid synthetase appearsto be characteristic of each individual mouse. In tumored mice fatty acid synthetase activity appears to be related to tumor weight, that is the larger the tumor the greater the activity. These results do not demonstrate support for a shift in the biosynthesis of saturated fatty acids in carcinomas. It may be that the altered lipid composition of the plasma membrane of tumor cells arises from the carcinoma's ability to utilize exogenous fatty acids.

Thesis (M.Phil.)--Chinese University of Hong Kong. / Bibliography: leaves 73-84.

No description available.

published_or_final_version / Chemistry / Master / Master of Philosophy

published_or_final_version / Chemistry / Master / Master of Philosophy

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Ka-leung Kan. / Thesis (M.Sc.)--Chinese University of Hong Kong. / Bibliography: leaves 80-94.

Age-related changes in the pH of the medium, fatty acid composition and biosynthesis of fatty acids in various subcellular fractions have been studied in submerged cultures of P. chrysogenum harvested at pH's 7.2, 4.8, 4.4 and 3.8. 14C - labeled lauric and myristic acids were each incubated with cell fractions prepared by sonification and fractional centrifugation. Products were analyzed by thin layer chromatography, gas liquid scintillation spectrometry. Conversion of labeled precursors into longer chain saturated and unsaturated fatty acids was employed as a measure of the activity of the various cell fractions.It was found that between pH 4.8 and 4.4 of the age of the culture a period of maximum fatty acid synthesis occured at the time when glucose was being taken up to a greatest extent from the medium and when cells start rapidly increasing in growth. This correlated to the increased rate of de novo synthesis in the soluble cytoplasmic fraction.The fermentation products, formic, acetic, proprionic, butyric and gluconic acid, produced at different time points of the age of the culture, accounted for the drop in the pH of the medium.