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The Role of Single-Nucleotide Polymorphisms in the Function of Candidate Tumor Suppressor ALDH1L1

Folate (vitamin B9) is a common name for a group of coenzymes that function as carriers of chemical moieties called one-carbon groups in numerous biochemical reactions. The combination of these folate-dependent reactions constitutes one-carbon metabolism, the name synonymous to folate metabolism. Fo...

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Autores principales: Krupenko, Sergey A., Horita, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831610/
https://www.ncbi.nlm.nih.gov/pubmed/31737034
http://dx.doi.org/10.3389/fgene.2019.01013
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author Krupenko, Sergey A.
Horita, David A.
author_facet Krupenko, Sergey A.
Horita, David A.
author_sort Krupenko, Sergey A.
collection PubMed
description Folate (vitamin B9) is a common name for a group of coenzymes that function as carriers of chemical moieties called one-carbon groups in numerous biochemical reactions. The combination of these folate-dependent reactions constitutes one-carbon metabolism, the name synonymous to folate metabolism. Folate coenzymes and associated metabolic pathways are vital for cellular homeostasis due to their key roles in nucleic acid biosynthesis, DNA repair, methylation processes, amino acid biogenesis, and energy balance. Folate is an essential nutrient because humans are unable to synthesize this coenzyme and must obtain it from the diet. Insufficient folate intake can ultimately increase risk of certain diseases, most notably neural tube defects. More than 20 enzymes are known to participate in folate metabolism. Single-nucleotide polymorphisms (SNPs) in genes encoding for folate enzymes are associated with altered metabolism, changes in DNA methylation and modified risk for the development of human pathologies including cardiovascular diseases, birth defects, and cancer. ALDH1L1, one of the folate-metabolizing enzymes, serves a regulatory function in folate metabolism restricting the flux of one-carbon groups through biosynthetic processes. Numerous studies have established that ALDH1L1 is often silenced or strongly down-regulated in cancers. The loss of ALDH1L1 protein positively correlates with the occurrence of malignant tumors and tumor aggressiveness, hence the enzyme is viewed as a candidate tumor suppressor. ALDH1L1 has much higher frequency of non-synonymous exonic SNPs than most other genes for folate enzymes. Common SNPs at the polymorphic loci rs3796191, rs2886059, rs9282691, rs2276724, rs1127717, and rs4646750 in ALDH1L1 exons characterize more than 97% of Europeans while additional common variants are found in other ethnic populations. The effects of these SNPs on the enzyme is not clear but studies indicate that some coding and non-coding ALDH1L1 SNPs are associated with altered risk of certain cancer types and it is also likely that specific haplotypes define the metabolic response to dietary folate. This review discusses the role of ALDH1L1 in folate metabolism and etiology of diseases with the focus on non-synonymous coding ALDH1L1 SNPs and their effects on the enzyme structure/function, metabolic role and association with cancer.
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spelling pubmed-68316102019-11-15 The Role of Single-Nucleotide Polymorphisms in the Function of Candidate Tumor Suppressor ALDH1L1 Krupenko, Sergey A. Horita, David A. Front Genet Genetics Folate (vitamin B9) is a common name for a group of coenzymes that function as carriers of chemical moieties called one-carbon groups in numerous biochemical reactions. The combination of these folate-dependent reactions constitutes one-carbon metabolism, the name synonymous to folate metabolism. Folate coenzymes and associated metabolic pathways are vital for cellular homeostasis due to their key roles in nucleic acid biosynthesis, DNA repair, methylation processes, amino acid biogenesis, and energy balance. Folate is an essential nutrient because humans are unable to synthesize this coenzyme and must obtain it from the diet. Insufficient folate intake can ultimately increase risk of certain diseases, most notably neural tube defects. More than 20 enzymes are known to participate in folate metabolism. Single-nucleotide polymorphisms (SNPs) in genes encoding for folate enzymes are associated with altered metabolism, changes in DNA methylation and modified risk for the development of human pathologies including cardiovascular diseases, birth defects, and cancer. ALDH1L1, one of the folate-metabolizing enzymes, serves a regulatory function in folate metabolism restricting the flux of one-carbon groups through biosynthetic processes. Numerous studies have established that ALDH1L1 is often silenced or strongly down-regulated in cancers. The loss of ALDH1L1 protein positively correlates with the occurrence of malignant tumors and tumor aggressiveness, hence the enzyme is viewed as a candidate tumor suppressor. ALDH1L1 has much higher frequency of non-synonymous exonic SNPs than most other genes for folate enzymes. Common SNPs at the polymorphic loci rs3796191, rs2886059, rs9282691, rs2276724, rs1127717, and rs4646750 in ALDH1L1 exons characterize more than 97% of Europeans while additional common variants are found in other ethnic populations. The effects of these SNPs on the enzyme is not clear but studies indicate that some coding and non-coding ALDH1L1 SNPs are associated with altered risk of certain cancer types and it is also likely that specific haplotypes define the metabolic response to dietary folate. This review discusses the role of ALDH1L1 in folate metabolism and etiology of diseases with the focus on non-synonymous coding ALDH1L1 SNPs and their effects on the enzyme structure/function, metabolic role and association with cancer. Frontiers Media S.A. 2019-10-30 /pmc/articles/PMC6831610/ /pubmed/31737034 http://dx.doi.org/10.3389/fgene.2019.01013 Text en Copyright © 2019 Krupenko and Horita http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Krupenko, Sergey A.
Horita, David A.
The Role of Single-Nucleotide Polymorphisms in the Function of Candidate Tumor Suppressor ALDH1L1
title The Role of Single-Nucleotide Polymorphisms in the Function of Candidate Tumor Suppressor ALDH1L1
title_full The Role of Single-Nucleotide Polymorphisms in the Function of Candidate Tumor Suppressor ALDH1L1
title_fullStr The Role of Single-Nucleotide Polymorphisms in the Function of Candidate Tumor Suppressor ALDH1L1
title_full_unstemmed The Role of Single-Nucleotide Polymorphisms in the Function of Candidate Tumor Suppressor ALDH1L1
title_short The Role of Single-Nucleotide Polymorphisms in the Function of Candidate Tumor Suppressor ALDH1L1
title_sort role of single-nucleotide polymorphisms in the function of candidate tumor suppressor aldh1l1
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831610/
https://www.ncbi.nlm.nih.gov/pubmed/31737034
http://dx.doi.org/10.3389/fgene.2019.01013
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