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Interactions Between Folate and Vitamin B12 in Maintenance of Genome Stability and Mitochondrial Function
Interactions Between Folate and Vitamin B12 in Maintenance of Genome Stability and Mitochondrial Function
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152659
- ISBN
- 9798384051671
- DDC
- 641
- 서명/저자
- Interactions Between Folate and Vitamin B12 in Maintenance of Genome Stability and Mitochondrial Function
- 발행사항
- [Sl] : Cornell University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 121 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
- 주기사항
- Advisor: Field, Martha.
- 학위논문주기
- Thesis (Ph.D.)--Cornell University, 2024.
- 초록/해제
- 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.
- 일반주제명
- Nutrition
- 일반주제명
- Biochemistry
- 일반주제명
- Molecular biology
- 일반주제명
- Genetics
- 키워드
- Genome stability
- 키워드
- Vitamin B12
- 키워드
- DNA replication
- 키워드
- Folate
- 기타저자
- Cornell University Nutrition
- 기본자료저록
- Dissertations Abstracts International. 86-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798384051671
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a641
■1001 ▼aHeyden, Katarina Elise.▼0(orcid)0000-0002-4731-6825
■24510▼aInteractions Between Folate and Vitamin B12 in Maintenance of Genome Stability and Mitochondrial Function
■260 ▼a[Sl]▼bCornell University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a121 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-03, Section: B.
■500 ▼aAdvisor: Field, Martha.
■5021 ▼aThesis (Ph.D.)--Cornell University, 2024.
■520 ▼aFolate (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.
■590 ▼aSchool code: 0058.
■650 4▼aNutrition
■650 4▼aBiochemistry
■650 4▼aMolecular biology
■650 4▼aGenetics
■653 ▼aMitochondrial function
■653 ▼aGenome stability
■653 ▼aVitamin B12
■653 ▼aDNA replication
■653 ▼aFolate
■690 ▼a0570
■690 ▼a0487
■690 ▼a0307
■690 ▼a0369
■71020▼aCornell University▼bNutrition.
■7730 ▼tDissertations Abstracts International▼g86-03B.
■790 ▼a0058
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17163371▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
