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

Previous work with cultured mammalian cells and perfused laboratory animals suggested to us that hydrolysis of homocysteine thiolactone was catalyzed in these systems. We confirmed this finding by measuring the sulfhydryl-releasing activity of cultured endothelial cells from human umbilical arteries in homocysteine thiolactone solution, pH 7.4, 37 degrees C. The reaction was vigorous and stereospecific and showed saturation kinetics (Km values for L- and D,L-homocysteine thiolactone were 3.9 and 8.2 mmol/l, respectively, and Vmax values were 10.75 and 10.1 mumol/min/10(9) cells, respectively). L-Homocysteine thiolactone was quantitatively converted to homocysteine, as measured by amino acid analysis. Human serum also accelerated the elimination of homocysteine thiolactone, although in this process, the majority of the newly formed sulfhydryl-containing product was precipitable by sulfosalicylic acid, indicating likely homocysteinylation of serum proteins. However, approximately 38% of the sulfhydryl-containing product was not precipitated, and because thiolactone elimination stereospecifically favored the L-enantiomer, a possible subsidiary role for serum-catalyzed hydrolysis of the thiolactone was suggested. No homocysteine thiolactone could be found in serum samples from six patients with acute myocardial infarction, three patients with cystathionine beta-synthase deficiency, and six normal subjects. Thus, humans have active vascular systems for elimination of homocysteine thiolactone, a process that could be responsible for an absence of the compound in serum.
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PMID:Homocysteine thiolactone disposal by human arterial endothelial cells and serum in vitro. 202 4

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