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)

Although the major biochemical abnormality due to methylenetetrahydrofolate reductase (MTHFR) deficiency is hyperhomocyst(e)inemia, its pathogenicity appears to involve more than homocysteine toxicity. In patients with severe MTHFR deficiency, a metabolite(s) other than hyperhomocyst(e)inemia also appears to be associated with its clinical manifestation in cerebrovascular disease. To elucidate the specific role of the TT genotype of MTHFR in the development of cerebral infarction with and without cognitive impairment, we determined the prevalence of hyperhomocyst(e)inemia and the C677T genotypes of MTHFR in 143 patients with vascular dementia, 122 patients with cerebral infarction, and 217 healthy subjects matched for age and sex. Prevalence of hyperhomocyst(e)inemia [homocyst(e)ine >/=15 micromol/L] was higher in cerebrovascular patients with or without dementia than in normal control subjects (42.6%, 20.5%, and 10.1%, respectively; P=0.001). In contrast, a higher frequency of MTHFR TT genotype was found only in demented patients compared with nondemented patients and healthy controls (25.2%, 9.8%, and 12.0%, respectively; P=0.01). When the study subjects were divided into normohomocyst(e)inemic and hyperhomocyst(e)inemic groups, the TT genotype was significantly associated with the risk for vascular dementia in the hyperhomocyst(e)inemic group (odds ratio 4.13, 95% CI 2.18 to 7.85; P=0.03) but not in the normohomocyst(e)inemic group. Demented patients with multiple infarcts had a higher frequency of TT genotype (odds ratio 3.13, 95% CI 2.23 to 4.39; P=0.0007), whereas those with a single infarct did not (odds ratio 2.03, P=0.15). In contrast, there was no significant association of the TT genotype with multiple infarcts in hyperhomocyst(e)inemic stroke patients. Taken together, these findings indicate a possible role of MTHFR TT genotype combined with hyperhomocyst(e)inemia in the pathogenesis of vascular dementia. Similar to the relationship between homocystinuria due to severe MTHFR deficiency and severe cystathionine beta-synthase deficiency, the TT genotype of MTHFR in hyperhomocyst(e)inemic subjects is differentiated from the cases of the TT genotype without hyperhomocyst(e)inemia or hyperhomocyst(e)inemia without the TT genotype in the development of cerebrovascular disease.
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PMID:Pathogenicity of thermolabile methylenetetrahydrofolate reductase for vascular dementia. 1093 12

In persons with Down's syndrome (DS) immunological abnormalities as well as hypothyroidism and Alzheimer type dementia are frequently observed. In addition, the activity of the enzyme cystathionine beta-synthase (CBS) is over-expressed which results in an altered homocysteine metabolism. In the present study, 48 older healthy DS persons without signs of dementia, psychiatric or somatic comorbidity and free of medication were analyzed for plasma levels of amino acids, neopterin and monoaminergic metabolites. Data were compared with those obtained from age and sex matched healthy controls. It was found that the spectrum of amino acids showed widespread differences in that levels of nearly all essential amino acids were lower in DS patients as compared to healthy controls. In addition, a significantly lower methionine and higher taurine concentration were observed which is in accordance with a disturbed homocysteine metabolism. With respect to the monoamine metabolites, the concentration of 5-hydroxyindoleacetic acid was not altered whereas that of homovanillic acid was significantly increased. Finally, the concentration of the immune activation marker neopterin was increased in persons with DS. It is concluded that healthy DS persons of older age show extensive biochemical abnormalities suggesting a compromised homocysteine metabolism, an activated cell-mediated immune response and an enhanced turnover of dopamine.
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PMID:Plasma amino acids and neopterin in healthy persons with Down's syndrome. 1740 39

The gaseous physiological modulator hydrogen sulfide (H2S) has recently been shown to exert a variety of neuroprotective effects. In particular, the treatment of transgenic mouse models of Alzheimer's disease (AD) with agents that release H2S aids preservation of cognitive function, suppresses brain production of amyloid beta, and decreases tau phosphorylation. The possible physiological relevance of these findings is suggested by the finding that brain and plasma levels of H2S are markedly lower in AD patients than matched controls. Hence, nutraceutical strategies which boost brain synthesis or levels of H2S may have potential for prevention of AD. The chief enzyme which synthesizes H2S in brain parenchyma, cystathionine beta-synthase (CBS), employs cysteine as its rate-limiting substrate, and is allosterically activated by S-adenosylmethionine (SAM). Supplemental taurine has been shown to boost expression of this enzyme, as well as that of another H2S source, cystathionine gamma-lyase, in vascular tissue, and to enhance plasma H2S levels; in rats subjected to hemorrhagic stroke, co-administration of taurine has been shown to blunt a marked reduction in brain CBS expression. Brain levels of SAM are about half as high in AD patients as in controls, and this is thought to explain the reduction of brain H2S in these patients. These considerations suggest that supplementation with cysteine, taurine, and agents which promote methyl group availability - such as SAM, folate, vitamin B12, and betaine - may have potential for boosting brain synthesis of H2S and thereby aiding AD prevention. Indeed, most of these agents have already demonstrated utility in mouse AD models - albeit the extent to which increased H2S synthesis contributes to this protection remains unclear. Moreover, prospective epidemiology has associated low dietary or plasma levels of folate, B12, and taurine with increased dementia risk. Rodent studies suggest that effective nutraceutical strategies for boosting brain H2S synthesis may in fact have broad neuroprotective utility, possibly aiding prevention and/or control not only of AD but also Parkinson's disease and glaucoma, while diminishing the neuronal damage associated with brain trauma or stroke.
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PMID:A diet rich in taurine, cysteine, folate, B12 and betaine may lessen risk for Alzheimer's disease by boosting brain synthesis of hydrogen sulfide. 3145 76