자료유형  

 학위논문

Control Number  

0017163371

International Standard Book Number  

9798384051671

Dewey Decimal Classification Number  

641

Main Entry-Personal Name  

Heyden, Katarina Elise.

Publication, Distribution, etc. (Imprint  

[S.l.] : Cornell University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

121 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-03, Section: B.

General Note  

Advisor: Field, Martha.

Dissertation Note  

Thesis (Ph.D.)--Cornell University, 2024.

Summary, Etc.  

요약Folate (vitamin B9) and vitamin B12 are essential nutrients that work together to support DNA replication and cell division. Recent concern has been raised over the potential for adverse health outcomes in individuals with excess folate exposure and low B12 status, but the molecular basis for these suggested links has not been evaluated. Further, the relationship between folate and B12 has been studied for decades- but primarily in the context of nuclear DNA synthesis and stability. This dissertation explores the interaction between folate and B12 in the context of excess folic acid and low B12, as well as the impact these nutrients have on mitochondrial DNA (mtDNA) stability. We observed that even when consumed at high doses, folic acid does not meaningfully accumulate in mouse tissues, though high-dose folic acid shifted folate vitamer distribution and elevated uracil in nuclear DNA of colon tissue. High-dose folic acid exposure did not affect liver total folate concentrations, vitamer distribution, or uracil levels in nuclear DNA. Additionally, we found that reduced expression of the B12-dependent enzyme methionine synthase (Mtr) caused uracil accumulation in mtDNA and impaired mitochondrial function in mouse liver. Further, we validated that dietary B12 deficiency led to uracil accumulation in mtDNA and impaired mitochondrial function in mouse skeletal muscle. We concluded that excess folic acid exposure has tissue-specific effects and that folate and B12 are essential to not only nuclear but also mtDNA integrity.

Subject Added Entry-Topical Term  

Nutrition.

Subject Added Entry-Topical Term  

Biochemistry.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Genetics.

Index Term-Uncontrolled  

Mitochondrial function

Index Term-Uncontrolled  

Genome stability

Index Term-Uncontrolled  

Vitamin B12

Index Term-Uncontrolled  

DNA replication

Index Term-Uncontrolled  

Folate

Added Entry-Corporate Name  

Cornell University Nutrition

Host Item Entry  

Dissertations Abstracts International. 86-03B.

Electronic Location and Access  

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Control Number  

joongbu:654310