Disease relevance of cystathionine

• Premature arteriosclerosis and thromboembolic events are well-known complications of homozygous homocystinuria due to cystathionine synthase deficiency [1].
• Of 11 transplantable and 7,12-dimethylbenz[a]anthracene-induced adenocarcinomas of the rat, all nonmetastasizing tumors could be distinguished from metastasizing tumors by the accumulation of high glutamine pools and significant-to-high cystathionine pools [2].
• Transcriptional regulation of the cystathionine-beta -synthase gene in Down syndrome and non-Down syndrome megakaryocytic leukemia cell lines [3].
• Characterization of cystathionine synthase as a selectable, liver-specific trait in rat hepatomas [4].
• In homozygous homocystinuria due to cystathionine synthase deficiency, characterized by severe hyperhomocysteinemia, there is a high incidence of vascular complications [5].

Psychiatry related information on cystathionine

• ABSTRACT : BACKGROUND : Cystathionine beta-synthase (CBS) mediates conversion of homocysteine to cystathionine and deficiency in enzyme activity may lead to hyperhomocysteinemia/homocystinuria, which are often associated with mental retardation (MR) [6].

High impact information on cystathionine

• In seven patients in each of the first two groups but in none of the patients in the third group, heterozygosity for homocystinuria was established on the basis of pathological homocysteinemia after methionine loading and cystathionine synthase deficiency in skin fibroblast cultures [1].
• Plasma levels of cystathionine and cysteine were significantly increased, consistent with an increase in CBS activity [7].
• Recent evidence suggested that mild homocyst(e)inemia, such as is present in heterozygotes for homocystinuria due to cystathionine synthase deficiency, may cause a marked excess in early ischemic heart disease [8].
• Effect of chronologic age on induction of cystathionine synthase, uroporphyrinogen I synthase, and glucose-6-phosphate dehydrogenase activities in lymphocytes [9].
• We have generated double knock-out mice with targeted deletions of the genes for apolipoprotein E (apoE) and cystathionine beta-synthase (CBS), which converts Hcy to cystathionine [10].

Chemical compound and disease context of cystathionine

• Cystathionine beta-synthase catalyzes the condensation of serine and homocysteine to yield cystathionine and is the single most common locus of mutations associated with homocystinuria [11].
• Onset of renal insufficiency was indicated by increasing values for 3-methylhistidine and cystathionine; multiple organ failure, by increased concentrations of methionine and phenylalanine in plasma [12].
• Mechanistic studies with vinylglycine and beta-haloaminobutyrates as substrates for cystathionine gamma-synthetase from Salmonella typhimurium [13].
• A cell extract of an extremely thermophilic bacterium, Thermus thermophilus HB8, cultured in a synthetic medium catalyzed cystathionine gamma-synthesis with O-acetyl-L-homoserine and L-cysteine as substrates but not beta-synthesis with DL-homocysteine and L-serine (or O-acetyl-L-serine) [14].
• Patients with homocystinuria due to cystathionine synthase deficiency do not have free homocystine in the liver when it is present in high concentrations in the plasma and the urine [15].

Biological context of cystathionine

• We used SSCP to survey reverse transcribed-PCR amplified cystathionine synthase cDNAs from patients with homocystinuria [16].
• Pyridoxal phosphate binding sites are similar in human heme-dependent and yeast heme-independent cystathionine beta-synthases. Evidence from 31P NMR and pulsed EPR spectroscopy that heme and PLP cofactors are not proximal in the human enzyme [17].
• 5. The appearance of an absorbance at 296 nm and quantitation of the products of oxidation in the presence of catalase indicate formation in the solutions of a seven-membered ketimine ring produced by cyclization of the monoamino monoketo derivative of cystathionine [18].
• BWTG3 hepatoma cells can acquire phenylalanine hydroxylase, cystathionine synthase and CPS-I without genetic manipulation, but activation of the silent OTC gene requires cell fusion with hepatocytes [19].
• These complexes support the proposed ping-pong mechanism for catalysis and illustrate the dissimilar substrate specificities of bacterial and plant cystathionine gamma-synthases on a molecular level [20].

Anatomical context of cystathionine

• Amino acid analysis confirmed the defect in SAA metabolism: homocystine, cysteine, cystathionine and serine were significantly decreased in frataxin-deficient cell extracts and mitochondria [21].
• Two specific inhibitors of carrier-mediated GSH extrusion, methionine or cystathionine, are able to decrease apoptotic GSH efflux across the intact plasma membrane, demonstrating that in these cell systems GSH extrusion occurs via a specific mechanism [22].
• Cystathionine beta-synthase is a soluble enzyme with a significant component occluded within the nerve endings [23].
• The content of cystathionine in each cerebellar region and pineal body increased gradually when the dose of DL-propargylglycine was increased from 10 mg to 30 mg per 200 g body weight [24].
• The subcellular distributions of the enzymes associated with the methylation and cystathionine-synthesizing portion of the sulfur amino acid metabolic pathway have been determined in the occipital lobe of the rhesus monkey [23].

Associations of cystathionine with other chemical compounds

• The five cystathionine synthase-deficient patients who had low residual activities of this enzyme detected in fibroblast and/or liver extracts did not lose more nitrogen or sulfur on diets virtually devoid of cystine than did the normal subjects [25].
• Homocysteine can also condense with serine to form cystathionine in a pyridoxal phosphate-dependent reaction catalyzed by cystathionine beta-synthase [26].
• Vitamin B12 and/or folate are significant predictors of tHcy, cystathionine, MMA, and AdoMet [27].
• Vitamin B12 was a significant determinant of concentrations of AdoMet, tHcy, methylmalonic acid (MMA), and cystathionine [27].
• We measured HCY, methylmalonic acid (MMA), and cystathionine by gas chromatography-mass spectrometry; S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) by liquid chromatography-tandem mass spectrometry; and the B-vitamins by HPLC or immunoassays [28].

Gene context of cystathionine

• The introduction of genes from Sac. cerevisiae constituting the cystathionine pathway (CYS4 and CYS3) into Sch. pombe Deltamet26 cells restored growth in the absence of adenine [29].
• CBS deficiency was ruled out by the presence of slightly elevated concentrations of plasma cystathionine [30].
• When the phylogeny was extended beyond the SNF4 gene family, SNF4 shares sequence similarity with other cystathionine-beta-synthase domain-containing proteins, including IMP dehydrogenase and a variety of uncharacterized Methanococcus proteins [31].
• These findings indicated that at least one reason of the high content of cystathionine in the 3 weeks rat cerebellum was due to the low level of cystathionine gamma-lyase [32].
• Conserved protein TTHA1554 from Thermus thermophilus HB8 binds to glutamine synthetase and cystathionine beta-lyase [33].

Analytical, diagnostic and therapeutic context of cystathionine

• A new sulfur-containing cyclic imino acid, cystathionine ketimine, has been detected in bovine cerebellum by gas chromatography, gas chromatography-mass spectrometry, and high pressure liquid chromatography procedures [34].
• After force-feeding the amino acid mixture, hepatic methionine, cystathionine and taurine were unaffected, and glutathione increased only at hours 3 and 4; glycine and threonine were elevated by 1.5 hours [35].
• Immobilization of Saccharomyces cerevisiae cystathionine gamma-lyase and application of the product to cystathionine synthesis [36].
• When EHDQ was measured in a mobile phase of pH 2.1 using high-performance liquid chromatography with ultraviolet detection, 250 pmol of L-cystathionine in 250 microliters of the reaction mixture could be determined [37].
• Determination of cystathionine in rat tissues using isotachophoresis [38].

References