Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.1.22 (cystathionine beta-synthase)
 965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The alterations of the metabolism of methionine determining an accumulation of homocysteine in blood (hyperhomocysteinemia) recognize a multifactorial etiology, hereditary as well as acquired. To date several case-control studies have documented that the condition of hyperhomocysteinemia can be considered an independent risk factor of coronary disease and its noxious effects are dose-dependent. It exerts its effect by different mechanisms both prothrombotic and endothelial. In our study we started from an initial cohort of 2227 subjects (1210 males, 1017 females) aged between 45 and 64 years among which we selected 22 persons with at least 2 first-degree relatives below age 50 who had had either a major cardiovascular event (acute myocardial infarction or sudden death) or angiographically documented cardiac disease. We reconstructed the proper pedigrees obtaining 22 families in whom we identified four main subgroups to carry out analyses and comparisons: case-control, composed respectively of all the subjects who survived a major cardiovascular event or a coronary disease documented angiographically and clinically healthy subjects; affected line and non affected line, composed respectively of members belonging to the family line of the proband and members of collateral family line. Each of the subjects involved in the study underwent a complete history regarding job and sports activities, a standardized physical examination, 12-lead digital ECG according to the European Standard Communication Protocol. A blood sample was taken in fasting conditions to determine total cholesterol, HDL and LDL cholesterol, triglycerides, glycemia, fibrinogen, plasma homocysteine. The results indicate how among the cases there were more subjects with homocysteine higher than the 95 degrees percentile in males alone (p = 0.03), the estimated odds ratio calculated from Fisher's test was 8.34 (95% confidence interval 1.32-52.7). Despite the fact that mean age was significantly lower (p = 0.01) in males of the affected line compared to those of the non affected line, the results show much higher homocysteine values in the affected family line in both males and females: a difference quite evident in the distribution especially as regards the 95 degrees percentile. These results obtained in the subjects belonging to the same families emphasize that familial aggregation, which influences the sharing of the genetic patrimony, socio-cultural environment and food habits can induce a differential risk for homocysteinemia. The study of mutations of genes coding for the key enzymes of the metabolism of homocysteine, methylenetetrahydrofolate reductase and cystathionine beta-synthase, which we prepared, will enable use to evaluate the relative influence feeding habits and genetic factors have in the development of hyperhomocysteinemia.
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PMID:[A hyperhomocysteinemia study in a population with a familial factor for acute myocardial infarct and sudden cardiac death at a young age]. 1018 34

We previously reported that hyperhomocysteinemia (HHcy), an independent risk factor of coronary artery disease (CAD), is associated with increased atherosclerosis and decreased plasma high-density lipoprotein cholesterol (HDL-C) in cystathionine beta-synthase-/apolipoprotein E-deficient (CBS(-/-)/apoE(-/-)) mice. We observed that plasma homocysteine (Hcy) concentrations are negatively correlated with HDL-C and apolipoprotein A1 (apoA-I) in patients with CAD. We found the loss of large HDL particles, increased HDL-free cholesterol, and decreased HDL protein in CBS(-/-)/apoE(-/-) mice, and attenuated cholesterol efflux from cholesterol-loaded macrophages to plasma in CBS(-/-)/apoE(-/-) mice. ApoA-I protein was reduced in the plasma and liver, but hepatic apoA-I mRNA was unchanged in CBS(-/-)/apoE(-/-) mice. Moreover, Hcy (0.5 to 2 mmol/L) reduced the levels of apoA-I protein but not mRNA and inhibited apoA-1 protein synthesis in mouse primary hepatocytes. Further, plasma lecithin:cholesterol acyltransferase (LCAT) substrate reactivity was decreased, LCAT specific activity increased, and plasma LCAT protein levels unchanged in apoE(-/-)/CBS(-/-) mice. Finally, the clearance of plasma HDL cholesteryl ester, but not HDL protein, was faster in CBS(-/-)/apoE(-/-) mice, correlated with increased scavenger receptor B1, and unchanged ATP-binding cassette transporter A1 protein expression in the liver. These findings indicate that HHcy inhibits reverse cholesterol transport by reducing circulating HDL via inhibiting apoA-I protein synthesis and enhancing HDL-C clearance.
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PMID:Hyperhomocysteinemia decreases circulating high-density lipoprotein by inhibiting apolipoprotein A-I Protein synthesis and enhancing HDL cholesterol clearance. 1697 11

Hyperhomocysteinemia (HHcy) is a significant and independent risk factor for cardiovascular disease (CVD) and the underlying mechanism is unclear. We and others have reported that homocysteine (Hcy) is inversely correlated with plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein AI (apoA-I) in patients with coronary heart disease (CHD). We confirmed this negative correlation in mice with targeted deletions of the genes for apolipoprotein E (apoE) and cystathionine beta-synthase (CBS). Severe HHcy (plasma Hcy 210 micromol/L) accelerates spontaneous arthrosclerosis in the CBS(-/-)/apoE(-/-) mice, reduces the concentration of circulating HDL, apoA-I, and large HDL particles, inhibits HDL function, and enhances HDL-C clearance. We have demonstrated further that Hcy (0.5-2 mmol/L) reduces apoA-I protein synthesis and secretion, but not RNA transcription in mouse primary hepatocytes. A different mechanism was proposed based on studies using the HepG2 cells showing that Hcy (5-10 mmol/L) inhibits apoA-I transcription via peroxisome proliferator-activated receptor-alpha (PPARalpha)-inhibition-dependent and -independent mechanisms. These studies suggest that Hcy-induced HDL-C and apoA-I inhibition represent a novel mechanism by which Hcy induces atherosclerotic CVD.
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PMID:Hyperhomocysteinemia and high-density lipoprotein metabolism in cardiovascular disease. 1802 Sep 70