Medical Sciences Commons^™

Alpha-Amino-Beta-Carboxy-Muconate-Semialdehyde Decarboxylase Controls Dietary Niacin Requirements For Nad+ Synthesis, Laura Palzer, Jessica J. Bader, Frances Angel, Megan Witzel, Sydney Blaser, Alexis Mcneil, Miles K. Wandersee, N. Adrian Leu, Christopher J. Lengner, Clara E. Cho, Kevin D. Welch, James B. Kirkland, Ralph G. Meyer, Mirella L. Meyer-Ficca

Animal, Dairy, and Veterinary Science Faculty Publications

NAD⁺ is essential for redox reactions in energy metabolism and necessary for DNA repair and epigenetic modification. Humans require sufficient amounts of dietary niacin (nicotinic acid, nicotinamide, and nicotinamide riboside) for adequate NAD⁺ synthesis. In contrast, mice easily generate sufficient NAD⁺ solely from tryptophan through the kynurenine pathway. We show that transgenic mice with inducible expression of human alpha-amino-beta-carboxy-muconate-semialdehyde decarboxylase (ACMSD) become niacin dependent similar to humans when ACMSD expression is high. On niacin-free diets, these acquired niacin dependency (ANDY) mice developed reversible, mild-to-severe NAD⁺ deficiency, depending on the nutrient composition of the diet. NAD deficiency …

Aflatoxin B1 Metabolism In Mammalian Pulmonary Tissue, J. Michael Eichelberger

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Aflatoxin B₁ (AFB₁) is a potent dietary hepatocarcinogen and may be a lung carcinogen when inhaled. To study the relative ability of lung and liver to metabolize AFB₁, a susceptible (Swiss-Webster rat) and resistant species (Syrian golden hamster) were pretreated with inducing agents in order to identify specific AFB₁ metabolizing enzymes in each tissue.

Analysis of AFB₁-exo-epoxide (AFBO) formation, O-dealkynation assays, and protein immunoblots demonstrated that cytochrome P450 (CYP) 1A proteins were overexpressed in both the lung and liver of hamsters pretreated with 3-methylchyolanthrene (3-MC). Only CYP1A1 was expressed in the lung …