Disease relevance of CTH

• Also, the availability of a common non-synonymous SNP can allow for testing of association of the CTH gene with biochemical traits affected by trans-sulfuration, such as plasma concentrations of homocysteine or even cystathionine itself, in addition to more downstream clinical phenotypes, such as vascular disease [1].
• It was shown previously that 5B5 bound a glycolipid named CTH (CD77) and its Ag was expressed on HK23- PNA+ tonsillar lymphocytes and Burkitt's lymphoma cell lines [2].
• The ratio of CTH and Digal-Cer to hydroxy fatty acid glucosyl ceramide was increased and seemed to be characteristic of Fabry disease [3].
• On the contrary the LH response to LH-RH and the testosterone response to HCG of the boys with unilateral cryptorchidism and without CTH were, as expected, significantly lower than in the control ones [4].
• Maternal gamma-cystathionase deficiency: absence of both teratogenic effects and pregnancy complications [5].

High impact information on CTH

• Cystathionine is subsequently cleaved to cysteine and alpha-ketobutyrate by the pyridoxal phosphate-dependent enzyme gamma-cystathionase [6].
• A-T homozygote lymphoblasts contained about 2-fold more gamma-cystathionase activity over other cell lines tested suggesting increased flux through the transsulfuration pathway for cysteine production in response to reduced cysteine supply [7].
• Reduced gamma-cystathionase protein content in human malignant leukemia cell lines as measured by immunoassay with monoclonal antibody [8].
• A murine hybrid cell line has been produced which secretes immunoglobulin G2b with specificity for human gamma-cystathionase (EC 4.2.1.15) [8].
• Endogenous hydrogen sulfide (H(2)S), generated from homocysteine metabolism mainly catalyzed by cystathionine gamma-lyase (CSE), possesses important functions in the cardiovascular system [9].

Chemical compound and disease context of CTH

• These findings suggest that (1) endogenous H2S is produced by myocardial ischemia in sufficient amounts to limit myocardial injury and (2) the synthesis or formation of H2S by cystathionine-gamma-lyase may contribute to the second window of protection caused by endotoxin [10].

Biological context of CTH

• In specimens from 12 Fabry heterozygotes, the total glycolipid fraction was increased (10 to 100-fold) and trihexosyl ceramide (CTH) was 2- to 70-fold times normal [3].
• Kinetics and inhibition of recombinant human cystathionine gamma-lyase. Toward the rational control of transsulfuration [11].
• Cell growth using homocysteine as a source of cysteine-sulphur requires two enzymes, cystathionine synthase (CS) and gamma-cystathionase (CT) [12].
• Identification of the active-site residue of gamma-cystathionase labeled by the suicide inactivator beta, beta, beta-trifluoroalanine [13].
• Transfection with the longer isoform increased the CGL activity 1.5-fold, while the activity of the cells transfected with the shorter form did not differ from the basal activity [14].

Anatomical context of CTH

• Thymocytes and peripheral blood lymphocytes (PBL) contain only traces of CTH and globoside, and PBL contain more CMH and CDH per cell than tonsil lymphocytes [15].
• This deficiency leads to the progressive accumulation, in lysosomes of visceral tissues and in body fluids of hemizygotes, of the glycosphingolipids globotriaosylceramide (CTH, Gb(3) or GL-3) and galabiosylceramide (CDH) and to a lesser extent the blood group AB and B related glycolipids [16].
• In smooth muscle cells, H2S produced by cystathionine gamma-lyase enhances the outward flux of potassium by opening potassium channels, leading to hyperpolarization of membrane potential and smooth muscle relaxation [17].
• We further showed for the first time cystathionine-gamma-lyase protein localization in the myocardium of the infarct area by using immunohistochemical staining [18].
• Because fetal tissues lack gamma-cystathionase, presumably cystathionine accumulated abnormally in the fetus and was transferred in abnormal amounts back to the mother [19].

Associations of CTH with chemical compounds

• Hereditary cystathioninuria (MIM 219500) is presumed to be caused by deficiency of the activity of cystathionine gamma-lyase (cystathionase; CTH EC 4.4.1.1), which is normally required for the conversion of methionine into cysteine [1].
• Recently, we discovered that cystathioninuria was caused by mutations in the CTH gene encoding cystathionine gamma-lyase, an enzyme that converts cystathionine to cysteine in the trans-sulfuration pathway [20].
• Cystathionine gamma-lyase (CSE) is a key enzyme in the trans-sulfuration pathway, which uses L-cysteine to produce hydrogen sulfide (H2S) [21].
• High but normal peaks of plasma LH and FSH were observed after LH-RH in CTH boys who showed a significant increase of testosterone after HCG stimulation [4].
• The levels of CTH and CDH were related to both creatinine and sphingomyelin [16].

Other interactions of CTH

• H(2)S was produced by trout bladders, and its production was sensitive to inhibitors of cystathionine beta-synthase and cystathionine gamma-lyase [22].
• Each affected child was homozygous for the novel DGUOK p.D255Y mutation, but had no CTH mutation, indicating that the hepatocerebral form of MDS might be associated with secondary cystathioninuria [23].
• Interaction between hydrogen sulfide/cystathionine gamma-lyase and carbon monoxide/heme oxygenase pathways in aortic smooth muscle cells [24].

Analytical, diagnostic and therapeutic context of CTH

• Mutants T6 and T24, obtained by gene replacement, showed an inactive mecB gene by Southern blot analysis and no cystathionine-gamma-lyase activity [25].
• In another set of experiments, administration of DL-propargylglycine (inhibitor of cystathionine gamma-lyase) to rats resulted in significant reduction in cavernous nerve stimulation-evoked perfusion pressure [26].
• A mouse monoclonal antibody has been produced which recognizes human liver gamma-cystathionase, Radioiodination of the monoclonal antibody facilitated its use in combination with non-specific precipitating rabbit antisera in classical immunodiffusion assays [27].

References