Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation
- PMID: 10884384
- DOI: 10.1074/jbc.M002725200
Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation
Abstract
S-Adenosylmethionine and S-adenosylhomocysteine (SAH), as the substrate and product of essential cellular methyltransferase reactions, are important metabolic indicators of cellular methylation status. Chronic elevation of SAH, secondary to the homocysteine-mediated reversal of the SAH hydrolase reaction, reduces methylation of DNA, RNA, proteins, and phospholipids. High affinity binding of SAH to the active site of cellular methyltransferases results in product inhibition of the enzyme. Using a sensitive new high pressure liquid chromatography method with coulometric electrochemical detection, plasma SAH levels in healthy young women were found to increase linearly with mild elevation in homocysteine levels (r = 0.73; p < 0.001); however, S-adenosylmethionine levels were not affected. Plasma SAH levels were positively correlated with intracellular lymphocyte SAH levels (r = 0.81; p < 0.001) and also with lymphocyte DNA hypomethylation (r = 0.74, p < 0.001). These results suggest that chronic elevation in plasma homocysteine levels, such as those associated with nutritional deficiencies or genetic polymorphisms in the folate pathway, may have an indirect and negative effect on cellular methylation reactions through a concomitant increase in intracellular SAH levels.
Similar articles
-
Measurement of plasma and intracellular S-adenosylmethionine and S-adenosylhomocysteine utilizing coulometric electrochemical detection: alterations with plasma homocysteine and pyridoxal 5'-phosphate concentrations.Clin Chem. 2000 Feb;46(2):265-72. Clin Chem. 2000. PMID: 10657384 Clinical Trial.
-
Elevation in S-adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanism for homocysteine-related pathology.J Nutr. 2002 Aug;132(8 Suppl):2361S-2366S. doi: 10.1093/jn/132.8.2361S. J Nutr. 2002. PMID: 12163693
-
Intracellular S-adenosylhomocysteine concentrations predict global DNA hypomethylation in tissues of methyl-deficient cystathionine beta-synthase heterozygous mice.J Nutr. 2001 Nov;131(11):2811-8. doi: 10.1093/jn/131.11.2811. J Nutr. 2001. PMID: 11694601
-
Role of S-adenosylhomocysteine in cardiovascular disease and its potential epigenetic mechanism.Int J Biochem Cell Biol. 2015 Oct;67:158-66. doi: 10.1016/j.biocel.2015.06.015. Epub 2015 Jun 24. Int J Biochem Cell Biol. 2015. PMID: 26117455 Review.
-
S-Adenosylhomocysteine: a better indicator of vascular disease than homocysteine?Am J Clin Nutr. 2007 Dec;86(6):1581-5. doi: 10.1093/ajcn/86.5.1581. Am J Clin Nutr. 2007. PMID: 18065573 Review.
Cited by
-
Evaluating the link between DIO3-FA27 promoter methylation, biochemical indices, and heart failure progression.Clin Epigenetics. 2024 Apr 24;16(1):57. doi: 10.1186/s13148-024-01668-0. Clin Epigenetics. 2024. PMID: 38659084 Free PMC article.
-
Epigenetic Genome Modifications during Pregnancy: The Impact of Essential Nutritional Supplements on DNA Methylation.Nutrients. 2024 Feb 28;16(5):678. doi: 10.3390/nu16050678. Nutrients. 2024. PMID: 38474806 Free PMC article. Review.
-
Global DNA Methylation Levels Viz-a-Viz Genetic and Biochemical Variations in One Carbon Metabolic Pathway: An Exploratory Study from North India.Biochem Genet. 2024 Feb 14. doi: 10.1007/s10528-023-10659-4. Online ahead of print. Biochem Genet. 2024. PMID: 38356009
-
Vitamin B12 Deficiency and the Nervous System: Beyond Metabolic Decompensation-Comparing Biological Models and Gaining New Insights into Molecular and Cellular Mechanisms.Int J Mol Sci. 2024 Jan 2;25(1):590. doi: 10.3390/ijms25010590. Int J Mol Sci. 2024. PMID: 38203763 Free PMC article. Review.
-
The Implication of a Polymorphism in the Methylenetetrahydrofolate Reductase Gene in Homocysteine Metabolism and Related Civilisation Diseases.Int J Mol Sci. 2023 Dec 22;25(1):193. doi: 10.3390/ijms25010193. Int J Mol Sci. 2023. PMID: 38203363 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources