All ETDs from UAB

Advisory Committee Chair

Charles Falany

Advisory Committee Members

Stephen Barnes

Michael Fallon

Natalia Kedishvili

Elias Meezan

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


The liver plays a central role in metabolism. It controls protein metabolism through deamination and transamination of amino acids, removal of ammonia through urea synthesis, synthesis of non-essential amino acids and synthesis of the majority of plasma proteins such as albumin. The liver regulates blood glucose levels through glyconeogenesis and glyconeolysis of glycogen, as well as gluconeogenesis from amino acids. It regulates fat metabolism through oxidation of triglycerides and fatty acids, as well as synthesis of cholesterol, lipoproteins, and phospholipids. Furthermore, the liver is the only site of formation of bile acids and their conjugates, physiologically important compounds that solubilize dietary fats (including cholesterol) and fat soluble vitamins. Bile acids are biological detergents, signaling hormones, and the end products of cholesterol metabolism. The production of bile acids from cholesterol represents the major route of excretion of cholesterol from the human body. The resulting metabolite possesses detergent properties and is toxic to cell membranes. Subsequently, bile acids must be excreted quickly from hepatocytes via amino acid conjugation, or amidation. Amidation decreases the pKa of a bile acid, forming a bile salt that can be soluble in the wide pH range of the enterohepatic circulation. In liver, amidation of bile acids with glycine or taurine is the final step in the biosynthesis of bile salts and is the result of the successive action of bile acid cholate CoA:Ligase (BAL) and bile acid CoA:N-acyltransferase (BAT). The biosynthesis of bile ii acids involves at least seventeen enzymes and four subcellular compartments, with each organelle and enzyme playing a defined role. The role of BAT is clear in bile acid synthesis, but its localization and within those organelles is still under debate. Understanding the distribution of BAT activity across the cell will provide insights into bile acid biosynthesis, the regulation of hepatic enzymes involved in conjugation, and the intracellular movement of proteins in general.



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