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De novo synthesis of NAD+ conrtibutes to reproductive development in Caenorhabditis elegans

Author:
Holleran, Lauren
Published:
[University Park, Pennsylvania] : Pennsylvania State University, 2017.
Physical Description:
1 electronic document
Additional Creators:
Hanna-Rose, Wendy and Schreyer Honors College
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Open Access.
Summary:
NAD+ is a molecule that is crucial in many different biochemical pathways across all organisms as an electron transporter. NAD+ also interacts with other proteins, such as sirtuins, which have been linked to aging and stress. In Caenorhabditis elegans, there are three biosynthetic pathways of NAD+, but my focus will be on a newly discovered pathway present in C. elegans, the de novo pathway. In this study, I will show through manipulation of this pathway that it contributes to reproductive development in C. elegans. In previous studies, it has been shown that blocking the salvage pathway of NAD+ synthesis with pnc-1 mutants results in a gonad delay phenotype. I have found that when knocking out both the de novo and salvage pathways with a umps-1;pnc-1 double mutant, the gonad delay phenotype is more penetrant. In pnc-1 mutants, supplementation with quinolinic acid (QA), a metabolite in the de novo pathway, has been shown to reverse the phenotype by increasing NAD+ levels. I show that supplementing umps-1;pnc-1 worms with QA does not fully reverse the phenotype since umps-1 is required to metabolize QA. In addition to the gonad delay phenotype, I focused on brood size, the number of progeny a single worm has, as an indicator of reproductive development. Also in the de novo pathway, kynu-1 mutants have a lower brood size than wild type. I show that supplementation of kynu-1 mutants with QA rescues the lowered brood size phenotype. I also supplement with nicotinic acid (NA), a metabolite in the salvage pathway. NA most likely increases NAD+, which partially reverses the NAD+-dependent phenotype.
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Dissertation Note:
B.S. Pennsylvania State University, 2017.
Technical Details:
The full text of the dissertation is available as an Adobe Acrobat .pdf file ; Adobe Acrobat Reader required to view the file.
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