Desulfhydrases desulfhydrase

L-cysteine (derivatives) /5-chloro-DL-alanine + Na2S Cys desulfhydrase Enterobactor cloacae 193... 

Nagasawa T, T Ishii, H Kumagai, H Yamada (1985) D-Cysteine desulfhydrase of Escherichia coli. Eur J Biochem 153 541-551. 

The enantiomers of this drug differ in their efficacy and activity, with (D)-penicilla-mine being the enantiomer required for pharmaceutical preparations. The (l)-enantiomer is toxic, and its absorption by the human body is more than the (D)-enantiomer. While both enantiomers of penicillamine are desulfhydrated by (r.)-cysteine desulfhydrase, only the (l)-isomer inhibits the action of this enzyme [2], The reported optical rotation values for (D)-penicillamine are ... 

Peak concentrations in the blood are obtained between 1 and 3 h after administration. Unlike cysteine (its nonmethylated parent compound), penicillamine is somewhat resistant to attack by cysteine desulfhydrase or L-amino acid oxidase. As a result, penicillamine is relatively stable in vivo [7,2],... 

Hydrogen sulfide is a well known general metabolite produced on sulfate reduction by certain bacteria. Moreover, organic forms of sulfur can give rise to HS , hence H2S in certain bacteria. Thus, cysteine desulfhydrase (EC 4.4.1.1, cystathionine y-lyase) converts L-cysteine to H2S, pyruvate, and NH3. This enzyme shows a requirement for pyridoxal phosphate and the unstable ami-noacrylic acid is an intermediate (Equation 1) in the reaction ... 

This pyridoxal-phosphate-dependent enzyme [EC 4.4.1.1] (also referred to as homoserine deaminase, homoserine dehydratase, y-cystathionase, cystine desulfhy-drase, cysteine desulfhydrase, and cystathionase) catalyzes the hydrolysis of cystathionine to produce cysteine, ammonia, and a-ketobutanoate (or, 2-oxobutanoate). 

L-/D-cvsteine. Hydrogen sulfide is produced from L-cysteine in a light-independent process that can be inhibited in vivo and in vitro by aminooxy acetic acid, an inhibitor of pyridoxal phosphate-dependent enzymes the hydrogen sulfide emitted in response to L-cysteine is directly derived from die L-cysteine fed ( 2 ). Therefore, hydrogen sulfide appears to be produced from L-cysteine by a pyridoxal phosphate-dependent, L-cysteine specific cysteine desulfhydrase. This conclusion is supported by the finding that in cucurbit... 

L-Cysteine desulfhydrase in leaves of cucurbit plants is a constitutive enzyme whose activity can be enhanced by preincubation of leaf discs with L-cysteine, D-cysteine, or structural analogs of L-cysteine at millimolar concentrations preincubation with cystine does not affect the activity of the enzyme (20.261. Although the stimulation of L-cysteine desulfhydrase activity is... 

S-Substituted L-cysteines Cysteine desulfhydrase Tryptophan synthase... 

This reaction is readily reversible. Another means of metabolizing serine, which accounts for its glucogenic character, as well as that of glycine, is the conversion of serine to pyruvate, as indicated in Figure 20.12. This reaction is catalyzed by serine dehydratase. A similar enzyme, threonine dehydratase, converts threonine to a-ketobutyrate, and the latter is then converted to propionyl-CoA, as indicated in Figure 20.13. Another similar enzyme, cysteine desulfhydrase, con-... 

There is a general requirement for pyridoxal-5-phosphate (24, 25, 27, 44) although not all of the activity lost on dialysis is restored by adding the cofactor. This requirement explains the inhibition by hydroxylamine and hydrazine (24, 25). The reaction is a typical pyridoxal-5-phosphate catalyzed a,/ -elimination with a mechanism similar to serine dehydrase and cysteine desulfhydrase (45). The coenzyme is probably bound as a Schiff base with an amino group of the enzyme since there is an absorption maximum at 415 nm in solutions of the purified garlic enzyme (40). The inhibition by L-cysteine is presumably caused by formation of a thiazolidine with the coenzyme (46). Added pyridoxal-5-phosphate also combines directly with the substrate. The dissociation constant for the complex is about 5 X lO M. When this is taken into account, the dissociation constant of the holoenzyme can be shown to be about 5 X 10 M (47). The higher enzyme activity in pyrophosphate buflFer than in Tris or phosphate may be explained by pyrophosphate chelation of metal ions which otherwise form tighter complexes with the substrate and coenzyme (47). This decreases the availability of added coenzyme. 

Other examples of PLP-requiring enzymes are the amino acid decarboxylases that lead to formation of amines, including several that are functional in nervous tissue (e.g., epinephrine, norepinephrine, serotonin, and y-aminobutyrate) cysteine desulfhydrase and serine hydroxymethyltransferase, which use PLP to effect the loss or transfer of amino acid side chains phosphorylase, which catalyzes phosphorolysis of the a-1,4-linkages of glycogen and cystathione beta-synthase in the transsulfiiration pathway of homocysteine. Additionally the biosynthesis of heme depends on the early... 

Wang, C. L., Lum, A. M., Ozuna, S. C., Clark, D. S., and Keasling, J. D. (2001). Aerobic sulfide production and cadmium precipitation by Escherichia coli expressing the Treponema denticola cysteine desulfhydrase gene. Appl. Microbiol. Biotechnol. 56, 425-430. 

Kredich, N.M., L.J. Foote, and B.S. Keenan. 1973. The stoichiometry and kinetics of the inducible cysteine desulfhydrase from Salmonella typhimurium.. Biol. Chem. 248 6187-6196. 

Degradation of L-cysteine by cysteine desulfhydrase or other PLP enzymes present in the cells was successfully prevented by addition of hydroxylamine or semi-carbazide to the incubation mixture. A mutant strain of Ps. thiazolinophilum lacking cysteine desulfhydrase was isolated and used to produce L-cysteine from d,l-ATC in a molar yield of 95% and at a product concentration of 31.4 g L 1[12S. Pseudomonas desmolytica A] 3872, one of the L-cysteine producers isolated was found to lack the ability to convert d-ATC into L-cysteine it is an ATC racemase-deficient strain 129l. However, little is known about the enzymological properties and function of the racemase. 

Cysteine has a number of potential metabolic pathways. With low cysteine intake, cysteine desulfhydrase may be of major importance. Cysteine desulfhydrase requires pyridoxal phosphate as a coenzyme and catalyzes the loss of H2S, similar to the loss of H20 with serine dehydratase. Thus, the final products are pyruvate, ammonia, and H2S. This pathway will produce pyruvate, a glucogenic precursor. However, the pathway, particularly with excess cysteine, must be limited, owing to the production of H2S, which is extremely toxic (Fig. 18.3). 

Enzymes that possess the same catalytic activity but are evolutionarily unrelated and play very diverse biological functions can be found, for example, in a group of PLP-dependent enzymes with desulfhydrase activity, that is, enzymes that release H2S from thiol amino acids. Bacteria employ desulfhydrases not only in the metabolism of sulfurated amino acids and in the adaptation to new nutrient sources, but also, sometimes, as virulence factors. An E. coli enzyme with desulfhydrase activity is even known to act as a modulator of gene expression, although this function seems to be unrelated to catalysis. Sulfide production by PLP-dependent enzymes is also important in vertebrates, where H2S has been shown to act as a neuromodulator. " ... 

PLP-dependent desulfhydrases necessarily show very similar mechanisms, but often come from independent evolutionary lineages. For example, although most bacterial L-cysteine desulfhydrases are fold-type I enzymes belonging to the same evolutionary branch as cystathionine f3- and 7-lyases, L-cysteine desulfhydrase from Fusobacterium nucleatum is a member of the fold-type II group and its closest sequence homologue is a cysteine synthase. D-cysteine desulfhydrase from E. coli is also a fold-type II enzyme not strictly related to other desulfhydrases but resembling instead an ACC deaminase. ... 

CICH2CH(NH2)C00H + Na2S cysteine desulfhydrase HSCH2CH(NH2)COOH... 

Reaction 3 is the cysteine desulfhydrase reaction which by -elimination produces HjS, pyruvate, and NH3. This reaction is catalyzed by cystathionine-y-lyase, the B protein of tryptophan synthetase (E.C. 4.2.1.20), or crystalline tryptophanase (E.C. 4.1.99.1) (Meister, 1965). According to Meister cysteine desulfhydrase reactions are probably catalyzed by other enzymes. Cystathionine-y-lyase has not been found in higher plants (Giovanelli et al., this volume. Chapter 12). 

Since even a slightly elevated L-cysteine concentration is inhibitory or possibly toxic for the cells E. coli possesses another mechanism for detoxification of this compound in addition to excretion degradation of L-cysteine. Five enzymes with L-cysteine desulfhydrase activity have been identified so far in this organism L-tryptophanase (TnaA), L-cystathionine p-lyase (MetC),... 

O-acetyl-L-serine (thiol)-lyase A (CysK), O-acetyl-L-serine (thiol)-lyase B (CysM) and MalY. Thus in order to engineer a potent L-cysteine over-producer excessive degradation of the amino acid must be prevented by inactivation of the genes encoding the major L-cysteine desulfhydrase activities. 

In all reactions, the first stage is formation of SchifTs base a by condensation of PalP and the amino acid. Schiff s bases a and b represent part of transamination, but for the complete mechanism see Transamination. Racemization a- b, followed by b-ia-iamino acid-1-PalP, with addition of the proton in the opposite configuration. Amino acid decarboxylation a -> d- c - amine + PalP. Serine hydroxymethyltransferase (EC 2.1.2.1) X = OH L-serine + PalP a f- g glycine + PalP reversal of these reactions leads to L-serine synthesis from glycine the hydroxymethyl group is carried by te-trahydrofolic acid. Cysteine desulfhydrase (EC 4.4.1.1) X = SH cy eine + PalP a b-> c-y hydro-... 

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