Dietetics and Clinical Nutrition Commons^™

Effects Of Single Nucleotide Polymorphisms In The Human Holocarboxylase Synthetase Gene On Catalytic Activity, Shingo Esaki

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

Holocarboxylase synthetase (HCS) catalyzes the covalent binding of biotin to carboxylases and histones in eukaryotic cells. Biotinylated carboxylases play essential roles in the metabolism of fatty acids, amino acids, and glucose; biotinylated histones play essential roles in gene regulation and genome stability. HCS null individuals are not viable whereas HCS deficiency is linked to developmental delays and phenotypes such as short life span and low stress resistance. Greater than 2,500 single nucleotide polymorphisms (SNPs) have been reported for HCS, but the biological importance of these polymorphisms is unknown. We hypothesized that some of these SNPs impair catalytic activity and that …

Regulation Of Sterol Transport By Dietary Phytosterol Esters, Trevor J. Carden

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

LDL cholesterol is associated with the development of atherosclerosis and is therefore considered an important target for intervention to prevent cardiovascular diseases. The inhibition of cholesterol absorption in the small intestine is an attractive approach to lowering plasma cholesterol, one that is exploited by drug therapy as well as dietary supplementation with plant sterols. The mechanism of action of plant sterol esters (PSE) is still incompletely understood, therefore this study was conducted to test the hypothesis that hydrolysis of plant sterol esters is necessary for their cholesterol-lowering effects to be realized.

Male Syrian hamsters were fed diets containing no PSE, …

Mechanisms Of Decreased Cholesterol Absorption Mediated By Phytosterols In The Intestinal Lumen, Andrew W. Brown

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

Phytosterols and their fatty acyl esters have been known for decades to lower LDL cholesterol, making them powerful nutraceuticals in lowering cardiovascular disease risk. The mechanisms by which phytosterols lower cholesterol, though, have been incompletely characterized. Three studies were executed to examine three aspects of cholesterol and phytosterol interactions in the intestinal lumen. In the first study, the ability of pancreatic cholesterol esterase to hydrolyze phytosterol esters was examined. Pancreatic cholesterol esterase hydrolyzed phytosterol esters, but the rate of hydrolysis proved sensitive to the structures of both the sterol and ester components. In the second study, cholesterol micellarization was challenged …

Regulation Of Atp Binding Cassette Transporter A1 And G1 Expression By Fatty Acids, Chai Siah Ku

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

High density lipoprotein (HDL) is an atheroprotective element which is critical in the reverse cholesterol transport (RCT) pathway to eliminate excess cholesterol from the periphery of the body. A low plasma HDL cholesterol levels indicate a higher risk of getting cardiovascular diseases (CVD). Formation and metabolism of HDL largely rely on ATP binding cassette transporter A1 (ABCA1) and G1 (ABCG1) that are transporters to facilitate the efflux of cellular cholesterol to outside of cells. ABCA1 in the liver and small intestine is the major contributing factor for HDL formation. On the other hand, ABCA1 and ABCG1 present in macrophages contribute …

Holocarboxylase Synthetase-Dependent Biotinylation Of Histone H4, Luisa F. Rios Avila

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

Holocarboxylase synthetase (HCS) catalyzes the binding of biotin to lysine (K) residues in histones H3 and H4. Histone biotinylation marks play important roles in the repression of genes and retrotransposons. Preliminary studies suggested that K16 in histone H4 is a target for biotinylation by HCS. Here we demonstrated that H4K16bio is overrepresented in repeat regions {pericentromeric alpha satellite repeats; long terminal repeats (LTR)} compared with euchromatin promoters. H4K16bio was also enriched in the repressed interleukin-2 gene promoter. The enrichment at LTR22 and promoter 1 of the sodium-dependent multivitamin transporter (SMVT) depended on biotin supply; and was significantly lower in fibroblasts …

Modulation Of Lipid Metabolism By Phytosterol Stearates And Black Raspberry Seed Oils, Mark Mckinley Ash

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

Naturally occurring compounds and lifestyle modifications as combination and mono-therapy are increasingly used for dyslipidemia. Specficially, phytosterols and fatty acids have demonstrated an ability to modulate cholesterol and triglyceride metabolism in different fashions. In two separate studies, the lipid-lowering effects of black raspberry seed oil and three different phytosterol stearates were examined in order to elucidate the effects of these dietary components and the factors influencing their therapeutic actions.

The first study examined high cholesterol diets supplemented with crude and refined black raspberry seed oils, coconut oil or soybean oil. The crude and refined raspberry seed oil (RSO) treatments significantly …