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. 2009 Apr 24;284(17):11601-12.
doi: 10.1074/jbc.M808026200. Epub 2009 Mar 4.

H2S biogenesis by human cystathionine gamma-lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia (V体育官网)

Taurai Chiku  1 , Dominique Padovani, Weidong Zhu, Sangita Singh, Victor Vitvitsky, Ruma Banerjee
Affiliations

H2S biogenesis by human cystathionine gamma-lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia

"VSports" Taurai Chiku et al. J Biol Chem. .

"V体育ios版" Abstract

Although there is a growing recognition of the significance of hydrogen sulfide (H(2)S) as a biological signaling molecule involved in vascular and nervous system functions, its biogenesis and regulation are poorly understood. It is widely assumed that desulfhydration of cysteine is the major source of H(2)S in mammals and is catalyzed by the transsulfuration pathway enzymes, cystathionine beta-synthase and cystathionine gamma-lyase (CSE). In this study, we demonstrate that the profligacy of human CSE results in a variety of reactions that generate H(2)S from cysteine and homocysteine. The gamma-replacement reaction, which condenses two molecules of homocysteine, yields H(2)S and a novel biomarker, homolanthionine, which has been reported in urine of homocystinuric patients, whereas a beta-replacement reaction, which condenses two molecules of cysteine, generates lanthionine VSports手机版. Kinetic simulations at physiologically relevant concentrations of cysteine and homocysteine, reveal that the alpha,beta-elimination of cysteine accounts for approximately 70% of H(2)S generation. However, the relative importance of homocysteine-derived H(2)S increases progressively with the grade of hyperhomocysteinemia, and under conditions of severely elevated homocysteine (200 microm), the alpha,gamma-elimination and gamma-replacement reactions of homocysteine together are predicted to account for approximately 90% of H(2)S generation by CSE. Excessive H(2)S production in hyperhomocysteinemia may contribute to the associated cardiovascular pathology. .

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V体育官网 - Figures

FIGURE 1.
FIGURE 1.
Cystathionine cleavage and H2S-generating reactions catalyzed by CSE.
FIGURE 2.
FIGURE 2.
Purification and characterization of recombinant human CSE. The UV-visible absorption spectrum of CSE (1.7 mg/ml in 70 mm Tris-HCl buffer, pH 8.1, containing 2 mm EDTA and 150 mm NaCl) exhibits a maximum at 428 nm due to PLP. Inset, purity of CSE (20 μg) detected on a 12% SDS-polyacrylamide gel by Coomassie Blue staining. The sizes of the molecular weight standards (M) are shown.
FIGURE 3.
FIGURE 3.
H2S generation by CSE. The reaction of H2S with lead acetate to form lead sulfide was monitored by the increase in absorbance at 390 nm under quasi-steady-state conditions, as described under “Experimental Procedures,” using as substrates 30 mm homocysteine (a), 30 mm homocysteine plus 10 mm cysteine (b), and 10 mm cysteine (c). Inset, in-gel activity staining of CSE. 40 μg of CSE was loaded in each lane and separated on a 4-15% native gradient gel, and H2S-producing activity was detected as described under “Experimental Procedures.” Although the major band corresponds to the native tetrameric form of CSE, a small proportion appear as high order oligomers. The molecular weight markers (M) were stained with Coomassie Blue.
FIGURE 4.
FIGURE 4.
Product analysis by MS of the CSE-catalyzed reactions in the presence of homocysteine plus cysteine (A), homocysteine alone (B), or cysteine alone (C). Parent ions with m/z values of 122 (cysteine), 136 (homocysteine), 209 (lanthionine), 223 (cystathionine), 237 (homolanthionine), 241 (cystine), and 269 (homocystine) are seen.
FIGURE 5.
FIGURE 5.
Kinetics of α-ketoacids and H2S generation by CSE in the presence of cysteine or homocysteine. Shown are the kinetics of pyruvate (A) (reaction 2) or α-ketobutyrate (C) (reaction 4) generation from cysteine or homocysteine, respectively. Also shown are kinetics of H2S generation from cysteine (B) (reactions 2 + 3) or from homocysteine (D) (reactions 4 + 5). The contributions of the component reactions (v2 and v3 in B and v4 and v5 in D) to the net rate of H2S generation are shown. Each data point represents the mean ± S.D. of at least three independent experiments. The data were analyzed as described under “Experimental Procedures,” and the kinetic parameters obtained from these plots are shown in Table 1.
FIGURE 6.
FIGURE 6.
The relative contributions of reactions 2-6 to H2S production at varying homocysteine concentrations. A, the rate of H2S production (○) observed in the presence of 10 mm cysteine and varying concentration of homocysteine in 0.1 m Hepes buffer, pH 7.4, at 37 °C. Each data point represents the mean ± S.D. of three independent experiments. The relative contributions of the individual reactions (v2-v6) to the net rate of H2S production (solid line) were simulated using the kinetic parameters reported in Table 1 and as described under “Experimental Procedures.” B, the contributions of the individual reactions (2-6) to H2S production by CSE were calculated at normal (10 μm), moderate (40 μm), and high (200 μm) concentrations of homocysteine and physiological concentrations of cystathionine and cysteine (5 and 100 μm, respectively) (Table 2). The reaction numbers are indicated above the bar graphs on the left. C, the relative proportions of CSE-derived H2S from cysteine versus homocysteine at three concentrations of homocysteine and physiological concentrations of cysteine and cystathionine (Table 3).
SCHEME 1.
SCHEME 1.
Postulated reaction mechanisms for CSE-catalyzed reactions with cysteine and homocysteine.
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References

    1. Wang, R. (2002) FASEB J. 16 1792-1798 - "VSports" PubMed
    1. Szabo, C. (2007) Nat. Rev. Drug Discov. 6 917-935 - "V体育ios版" PubMed
    1. Li, L., Bhatia, M., and Moore, P. K. (2006) Curr. Opin. Pharmacol. 6 125-129 - PubMed
    1. Goodwin, L. R., Francom, D., Dieken, F. P., Taylor, J. D., Warenycia, M. W., Reiffenstein, R. J., and Dowling, G. (1989) J. Anal. Toxicol. 13 105-109 - PubMed
    1. Abe, K., and Kimura, H. (1996) J. Neurosci. 16 1066-1071 - "VSports最新版本" PMC - PubMed

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