Reactions catalysed by serine sulfhydrase from chicken liver

Braunstein, A. E.; Goryachenkova, E.V.; Định, Nguyễn Văn

doi:10.1016/0005-2744(69)90173-9

Cited by 50 publications

(28 citation statements)

References 3 publications

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“…As with yCBS, reaction 4 is a much more significant contributor to H 2 S production being ϳ41-and ϳ23-fold more efficient than reactions 2 and 3, respectively. The observed increase in the specific activity of hCBS with cysteine versus cysteine and homocysteine as substrates is similar to the 30-fold difference reported by Braunstein et al (27). The turnover number of H 2 S generation from reaction 4 is ϳ2.8-fold higher for yeast versus human CBS (Table 1).…”

Section: Initial Analysis Of H 2 S Production By Hcbs and Ycbs-supporting

confidence: 73%

Relative Contributions of Cystathionine β-Synthase and γ-Cystathionase to H2S Biogenesis via Alternative Trans-sulfuration Reactions

Singh

Padovani

Leslie

et al. 2009

Journal of Biological Chemistry

569

507

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In mammals, the two enzymes in the trans-sulfuration pathway, cystathionine ␤-synthase (CBS) and cystathionine ␥-lyase (CSE), are believed to be chiefly responsible for hydrogen sulfide (H 2 S) biogenesis. In this study, we report a detailed kinetic analysis of the human and yeast CBS-catalyzed reactions that result in H 2 S generation. CBS from both organisms shows a marked preference for H 2 S generation by ␤-replacement of cysteine by homocysteine. The alternative H 2 S-generating reactions, i.e. ␤-elimination of cysteine to generate serine or condensation of 2 mol of cysteine to generate lanthionine, are quantitatively less significant. The kinetic data were employed to simulate the turnover numbers of the various CBS-catalyzed reactions at physiologically relevant substrate concentrations. At equimolar concentrations of CBS and CSE, the simulations predict that H 2 S production by CBS would account for ϳ25-70% of the total H 2 S generated via the trans-sulfuration pathway depending on the extent of allosteric activation of CBS by S-adenosylmethionine. The relative contribution of CBS to H 2 S genesis is expected to decrease under hyperhomocysteinemic conditions. CBS is predicted to be virtually the sole source of lanthionine, and CSE, but not CBS, efficiently cleaves lanthionine. The insensitivity of the CBS-catalyzed H 2 S-generating reactions to the grade of hyperhomocysteinemia is in stark contrast to the responsiveness of CSE and suggests a previously unrecognized role for CSE in intracellular homocysteine management. Finally, our studies reveal that the profligacy of the trans-sulfuration pathway results not only in a multiplicity of H 2 S-yielding reactions but also yields novel thioether metabolites, thus increasing the complexity of the sulfur metabolome.

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Section: Initial Analysis Of H 2 S Production By Hcbs and Ycbs-supporting

confidence: 73%

Relative Contributions of Cystathionine β-Synthase and γ-Cystathionase to H2S Biogenesis via Alternative Trans-sulfuration Reactions

Singh

Padovani

Leslie

et al. 2009

Journal of Biological Chemistry

569

507

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“…The mechanism by which 33 S-cystathionine is formed from 35 S-cysteine is not clear. Cysteine, in place of serine, can serve as cosubstrate with homocysteine in the synthesis of cystathionine by serine sulfhydrase, which may be identical with cystathionine synthase [1], but in this reaction the sulfur atom of cystathionine is derived from homocysteine and nonradioactive cystathionine would be formed from 30 S-cysteine. In the presence of homoserine, the sulfur atom from cysteine is incorporated into cystathionine by cystathionase acting in the reverse direction [9], and, indeed, a crude extract of liver from a premature infant was able to synthesize cystathionine in vitro [9], but cystathionase is lacking in fetal liver.…”

Section: Radioactive Studiesmentioning

confidence: 99%

“…Another possibility would be to invoke the presence of a separate "homoserine sulfhydrase" (cf. [1]) which would form 35 S-cystathionine from 35 Scysteine and either homocysteine or homoserine by y cleavage.…”

Section: Radioactive Studiesmentioning

confidence: 99%

Development of Mammalian Sulfur Metabolism: Absence of Cystathionase in Human Fetal Tissues

1972

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ExtractCystathionase activity was absent from human fetal liver and brain as early as 6 weeks of gestation. Hepatic methionine-activating enzyme (26 ± 3 nmoles/mg protein/hr) and hepatic cystathionine synthase (21 ± 4 nmoles/mg protein/hr) were present (cf. 86 ±16 and 98 ± 19 nmoles/mg protein/hr, respectively, in mature human liver). All three activities were absent from the placenta. Human fetal liver contained higher concentrations of cystathionine (14 ± 2 /xmoles/100 g wet weight) than mature human liver (0) and human fetal brain (4.0 ± 0.6 ,umoles/100 g wet weight). Methionineactivating enzyme of human fetal brain, but not liver, showed a tendency to increase with development (coefficient of correlation was 0.62; 0.01 < P < 0.05).35 S-L-methionine injected into the umbilical vein of six human fetuses was incorporated into free methionine in liver and brain, but not into free cyst(e)ine, homocyst(e)ine, taurine or, except for the smallest fetus, cystathionine. 35S-L-cysteine similarly injected was incorporated into free cysteine in liver and brain to a greater extent than in plasma, whereas it was incorporated into cystine in plasma to a greater extent than in either liver or brain. Incorporation of S-L-cysteine incubated with minced liver from four human fetuses showed more active incorporation of methionine (11,836-15,045 dpm/mg protein) than cysteine (7,044-9,856 dpm/mg protein). SpeculationThese studies suggest that cysteine is an essential amino acid in human fetuses and in infants for some time after birth, especially if they were born prematurely. Introductionknown about the early development of these pathways. Although there is considerable information on controlIn normal adult humans, about 90% of ingested meof the metabolism of sulfur-containing amino acids thionine is converted to cyst(e)ine [21], a nonessential and transsulfuration in mature humans, little is amino acid, via the transsulfuration pathway (Fig. 1).

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“…Cyanoalanine synthase catalyzes slow isotopic a-H exchange in cysteine and in end-product amino acids; the rates of a-H exchange in nonreacted (excess) cysteine are markedly increased in the presence of an adequate cosubstrate; no exchange is observed of H atoms in f3-position. In recent years we made comparative studies of some vitamin-B6-dependent lyases exclusively catalyzing replacement reactions of l-substituent in cysteine, serine, and related analogs (8,9,18,19,25). As a rule, these lyases, e.g., cysteine lyase (EC 4.4.1.10), serine sulfhydrase, and the identical or closely similar cystathionine j3-synthase (EC 4.2.1.22), use aliphatic thiols as cosubstrates (replacing agents).…”

mentioning

confidence: 99%

Beta-cyanoalanine synthase: purification and characterization.

Akopyan¹,

Braunstein²,

Goryachenkova³

1975

Proc. Natl. Acad. Sci. U.S.A.

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Beta-cyano-L~alanine synthase iL-cysteine hydrogen-sulfide-lyase (adding HCN), EC 4.4.1.91 was purified about 4000-fold from blue lupine seedlings. The enzyme was homogeneous on gel electrophoresis and free of contamination by other pyridoxal-P-dependent lyases. The enzyme has a molecular weight of 52,000 and contains 1 mole of pyridoxal-P per mole of protein; its isoelectric point is situated at pH 4.7. Its absorption spectrum has two maxima, at 280 and 410 nm. L-Cysteine is the natural primary (amino acid) substrate; jB-chloro-and ,3-thiocyano-L-alanine can substitute for it. Some small aliphatic thiols can serve (with considerably lower affinity) instead of cyanide as cosubstrates for cyanoalanine synthase. The synthase is refractory to DL-cycloserine and D-penicillamine, potent inhibitors of many pyridoxal-P-dependent enzymes. Cyanoalanine synthase catalyzes slow isotopic a-H exchange in cysteine and in end-product amino acids; the rates of a-H exchange in nonreacted (excess) cysteine are markedly increased in the presence of an adequate cosubstrate; no exchange is observed of H atoms in f3-position. In recent years we made comparative studies of some vitamin-B6-dependent lyases exclusively catalyzing replacement reactions of l-substituent in cysteine, serine, and related analogs (8,9,18,19,25). As a rule, these lyases, e.g., cysteine lyase (EC 4.4.1.10), serine sulfhydrase, and the identical or closely similar cystathionine j3-synthase (EC 4.2.1.22), use aliphatic thiols as cosubstrates (replacing agents). It seemed of particular interest to extend our studies to (CN)Ala synthase, a jB-lyase utilizing cyanide as the preferred cosubstrate.Abbreviations: Pyridoxal-P, pyridoxal-5'-phosphate; (CN)Ala, fl-cyano-L-alanine; (Cl)Ala, B-chloroalanine; (CNS)Ala, fl-thiocyano-i>alanine; HS-EtOH, 2-mercaptoethanol; r.s.r., relative specific radioactivity. 1617 In this paper, we present an improved purification procedure for (CN)Ala synthase, and report on some general and catalytic properties of the enzyme. MATERIALS AND METHODSReagents and Instruments. All chemicals were preparations of highest purity available, namely: DEAE-Sephadex A-50 and Sephadex G-100 (Pharmacia, Uppsala); hydroxylapatite from Bio-Rad; pyridoxal-P (Reanal, Budapest); dansyl chloride (Merck); reference dansylamino acids (from "Serva"); 3H20 (61 mCi/ml), made in USSR. Aluminum hydroxide C.) was prepared according to Willstatter and Kraut (27). We thank Dr. Drell (Calbiochem) for the gift of a sample of ,B-cyanoalanine.Reagents and apparatus for analytical gel electrophoresis were supplied by Reanal; Ampholine buffers and equipment for isoelectrofocusing, by LKB Producter (Stockholm).Chromatographic and electrophoretic separations were performed on papers FN-4 and FN-16 ("Filtrak", German Democratic Republic). All buffer solutions used were Tris HC1 of pH 8.8, in the concentrations indicated.Enzyme Activity Assays. (CN)Ala synthase activity assays were based on the rates of formation of end-products-H2S, (CN

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Reactions catalysed by serine sulfhydrase from chicken liver

Cited by 50 publications

References 3 publications

Relative Contributions of Cystathionine β-Synthase and γ-Cystathionase to H2S Biogenesis via Alternative Trans-sulfuration Reactions

Relative Contributions of Cystathionine β-Synthase and γ-Cystathionase to H2S Biogenesis via Alternative Trans-sulfuration Reactions

Development of Mammalian Sulfur Metabolism: Absence of Cystathionase in Human Fetal Tissues

Beta-cyanoalanine synthase: purification and characterization.

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