Hyperhomocysteinemia:An Emerging and Important Risk Factor for Thromboembolic and Cardiovascular Disease

Abstract

Homocysteine is an important contributing factor to thrombosis, vascular injury, and vascular disease. Mechanisms for homocysteine-induced vascular disease include alterations in coagulation as well as endothelial cell and vessel wall injury. Hyperhomocysteinemia (HH|e|) can occur when homocysteine metabolism is altered by mutations in enzymes responsible for homocysteine metabolism. CharacterizationHomocysteine is a thiol-containing amino acid metabolized by remethylation to methionine or by transsulfuration to cysteine. Elevated homocysteine levels may occur as a result of inherited disorders that alter enzyme activity in the transsulfuration and remethylation pathways. Alternatively, nutritional deficiencies of cobalamin (vitamin B 12 ), folate, or pyridoxine (vitamin B 6 ), can result in blockade of homocysteine metabolic pathways, because activity of these enzymes depends on these vitamins as cofactors. Clinically, elevated homocysteine levels are significant because they may indicate cobalamin, pyridoxine, or folate deficiency. More importantly, elevated homocysteine levels are an independent risk factor for thrombosis and vascular disease.1 "".Homocysteine is the reduced (sulfhydryl) form and homocystine the oxidized (disulfide) form of the homologues cysteine and cystine. 312 For the purpose of this review, both forms of "homocysteine" will be referred to as H(e) and hyperhomocyst(e)inemia as HH(e). In patients in whom H(e) levels are normal, only about 2% of the total concentration occurs as the sulfhydryl form. With elevated H(e) levels, the percentage of homocysteine in the sulfhydryl form represents an increasing per-

Choline: Critical Role During Fetal Development and Dietary Requirements in Adults

“…Similarly it influences neural tube development (40,112). In later life, choline deficiency causes fatty liver as well as liver and muscle damage (33,159), and reduces the capacity to handle a methionine load, resulting in elevated homocysteine (34), a risk factor for cardiovascular disease (46). Though many foods contain choline (160,162), there is at least a twofold variation in dietary intake in humans (39,112).…”

Possíveis mecanismos trombogênicos da hiper-homocisteinemia e o seu tratamento nutricional

“…A suplementação de folato é um meio barato e eficaz na redução dos níveis de homocisteína plasmática 23 . A dose exata de folato, cobalamina e piridoxina necessária para o tratamento da hiper-homocisteinemia ainda não foi determinada, sendo que diferentes doses dessas vitaminas têm sido utilizadas em muitos estudos 24 . Na maioria dos pacientes, pequenas doses de folato (1.000µg a 5.000µg/dia) reduzem rapidamente os níveis de homocisteína plasmática 11 .…”

“…Em muitos casos, torna-se necessária a combinação de folato, piridoxina e cobalamina no tratamento da hiper-homocisteinemia 24 . A combinação de folato (650µg/dia), piridoxina (10mg/dia) e cobalamina (400µg/dia) demonstrou ser bastante eficiente nos casos de hiperhomocisteinemia moderada 26 .…”

Recombinant adeno-associated virus mediated gene transfer in a mouse model for homocystinuria

“…Moreover, it perturbs the methylation cycle, such as the intracellular accumulation of S-adenosyl homocysteine, which has consequences for cell metabolism . Elevated homocysteine levels are a potential risk factor for cardiovascular disease (Guba et al, 1996;Robert et al, 2003b), and several studies have…”