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Metabolic interactions among amino acids, phospholipids and fatty acids

University of British Columbia

Cystic fibrosis (CF) is the most common life-shortening disorder among Caucasians. Excessive faecal bile acid loss, increased oxidant stress, reduced plasma choline, increased oxidant stress, reduced glutathione and alterations in essential fatty acids are well recognized in patients with CF. It is also well-known that diabetes perturbs the methionine-homocysteine cycle. However, experimental data linking loss of amino acids in CF or decreased glucose availability in experimental diabetes to altered phospholipids and fatty acid metabolism are lacking. In the liver, bile acids are conjugated with glycine or taurine prior to secretion, and glycine de novo synthesis begins with glucose. Thus, the objectives of this thesis are: 1) to determine if inducing faecal bile acid loss will alter the methionine-homocysteine, and choline-betaine cycle metabolites, phospholipids and phospholipids n-6 and n-3 fatty acids, and 2) to show that experimental diabetes, which decreases glucose availability, alters methionine-homocysteine and choline-betaine cycle metabolites, phospholipids and phospholipid fatty acids in rats. Studies to address the first objective demonstrated that inducing faecal bile acid malabsorption leads to fat malabsorption with increased faecal total lipids and phospholipid excretion. This increased excretion was accompanied by increased plasma betaine concentration, decreased plasma triacylglycerol concentration, increased plasma and liver S-adenosylhomocysteine (SAH) concentration, and changes in the fatty acid composition of hepatic phospholipids. Studies to address the second objective showed that experimental diabetes led to increased plasma betaine concentration, decreased homocysteine concentration, increased liver phosphatidylethanolamine, decreased phosphatidylcholine, changes in the fatty acid composition of hepatic phospholipids, and abundance of the enzyme choline dehydrogenase. Thus, experimental diabetes, which reduces intracellular glucose availability, alters methionine-homocysteine and choline-betaine cycle metabolites, phospholipids and fatty acids. In conclusion, metabolism of phospholipids, their fatty acids, and the amino acids involved in the methionine-homocysteine cycle are inter-related.

Text

2013-10-07

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/45211

Human Nutrition

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/