The Link Between Hyperhomocysteinemia and Hypomethylation: Implications for Cardiovascular Disease
Standard
The Link Between Hyperhomocysteinemia and Hypomethylation: Implications for Cardiovascular Disease. / Barroso, Madalena; Handy, Diane E; Castro, Rita.
In: Journal of Inborn Errors of Metabolism and Screening (JIEMS), Vol. 5, 05.04.2020.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - The Link Between Hyperhomocysteinemia and Hypomethylation: Implications for Cardiovascular Disease
AU - Barroso, Madalena
AU - Handy, Diane E
AU - Castro, Rita
PY - 2020/4/5
Y1 - 2020/4/5
N2 - ncreased levels of homocysteine have been established as a risk factor for cardiovascular disease (CVD) by mechanisms still incompletely defined. S-Adenosylhomocysteine (SAH) is the metabolic precursor of homocysteine that accumulates in the setting of hyperhomocysteinemia and is a negative regulator of most cell methyltransferases. Several observations, summarized in the current review, support the concept that SAH, rather than homocysteine, may be the culprit in the CVD risk that has been associated with hyperhomocysteinemia. This review examines the biosynthesis and catabolism of homocysteine and how these pathways regulate accumulation of SAH. In addition, the epidemiological and experimental links between hyperhomocysteinemia and CVD are discussed, along with the evidence suggesting a role for SAH in the disease. Finally, the effects of SAH on the hypomethylation of DNA, RNA, and protein are examined, with an emphasis on how specific molecular targets may be mediators of homocysteine-associated vascular disease.
AB - ncreased levels of homocysteine have been established as a risk factor for cardiovascular disease (CVD) by mechanisms still incompletely defined. S-Adenosylhomocysteine (SAH) is the metabolic precursor of homocysteine that accumulates in the setting of hyperhomocysteinemia and is a negative regulator of most cell methyltransferases. Several observations, summarized in the current review, support the concept that SAH, rather than homocysteine, may be the culprit in the CVD risk that has been associated with hyperhomocysteinemia. This review examines the biosynthesis and catabolism of homocysteine and how these pathways regulate accumulation of SAH. In addition, the epidemiological and experimental links between hyperhomocysteinemia and CVD are discussed, along with the evidence suggesting a role for SAH in the disease. Finally, the effects of SAH on the hypomethylation of DNA, RNA, and protein are examined, with an emphasis on how specific molecular targets may be mediators of homocysteine-associated vascular disease.
U2 - 10.1177/2326409817698994
DO - 10.1177/2326409817698994
M3 - SCORING: Review article
VL - 5
JO - J Inborn Err Metab Scr (JIEMS)
JF - J Inborn Err Metab Scr (JIEMS)
SN - 2326-4098
ER -