O-Acetylserine

In a series of papers, Cook et al.60-63 presented results of the 31P NMR studies of pyridoxal 5 -phosphate dependent enzyme. O-acetylserine sulf-hydrylase is the enzyme which catalyses the final step of biosynthesis of l-cysteine, the replacement of p-acetoxy group of O-acetyl-L-serine by thiol [30] in bacteria and plants. 

This enzyme [EC 4.2.99.10], also referred to as O-acetyl-homoserine sulfhydrylase, catalyzes the reaction of O-acetylhomoserine with methanethiol to generate methionine and acetate. The enzyme can also act on other thiols or H2S, producing homocysteine or thioethers. The enzyme isolated from baker s yeast will also catalyze the reaction exhibited by O-acetylserine (thiol)-lyase [EC 4.2.99.8], albeit more slowly. 

This enzyme [EC 4.2.99.8], also known as cysteine synthase and O-acetylserine sulfhydrylase, catalyzes the pyr-idoxal-phosphate-dependent reaction of H2S with O -acetylserine to produce cysteine and acetate. Some alkyl thiols, cyanide, pyrazole, and some other heterocyclic compounds can also act as acceptors. 

PHOSPHATE ACETYLTRANSFERASE PYRUVATE OXIDASE O-Acetylserine sulfhydralase,... 

ACETYLSERINE (THIOL)-LYASE O-ACETYLSERINE (THIOL)-LYASE Acetylserotonin methyltransferase. 

Cystathionine (3-lyase (cystathionase) O-Acetylserine sulfhydrylase (cysteine synthase)... 

Beta replacement is catalyzed by such enzymes of amino acid biosynthesis as tryptophan synthase (Chapter 25),184 O-acetylserine sulfhydrylase (cysteine synthase),185 186a and cystathionine (3-synthase (Chapter 24).187 188c In both elimination and (3 replacement an unsaturated Schiff base, usually of aminoacrylate or aminocrotonate, is a probable intermediate (Eq. 14-29). Conversion to the final products is usually assumed to be via hydrolysis to free aminoacrylate, tautomerization to an imino acid, and hydrolysis of the latter, e.g., to pyruvate and ammonium ion (Eq. 14-29). However, the observed stereospecific addition of a... 

Cysteine is formed in plants and in bacteria from sulfide and serine after the latter has been acetylated by transfer of an acetyl group from acetyl-CoA (Fig. 24-25, step f). This standard PLP-dependent (3 replacement (Chapter 14) is catalyzed by cysteine synthase (O-acetylserine sulfhydrase).446 447 A similar enzyme is used by some cells to introduce sulfide ion directly into homocysteine, via either O-succinyl homoserine or O-acetyl homoserine (Fig. 24-13). In E. coli cysteine can be converted to methionine, as outlined in Eq. lb-22 and as indicated on the right side of Fig. 24-13 by the green arrows. In animals the converse process, the conversion of methionine to cysteine (gray arrows in Fig. 24-13, also Fig. 24-16), is important. Animals are unable to incorporate sulfide directly into cysteine, and this amino acid must be either provided in the diet or formed from dietary methionine. The latter process is limited, and cysteine is an essential dietary constituent for infants. The formation of cysteine from methionine occurs via the same transsulfuration pathway as in methionine synthesis in autotrophic organisms. However, the latter use cystathionine y-synthase and P-lyase while cysteine synthesis in animals uses cystathionine P-synthase and y-lyase. 

Fig. 24-25), another component of nervous tissue. Cysteic acid can arise in an alternative way from O-acetylserine and sulfite (reaction 1, Fig. 24-25), and taurine can also be formed by decarboxylation of cysteine sulfinic acid to hypotaurine and oxidation of the latter (reaction m). Cysteic acid can be converted to the sulfolipid of chloroplasts (p. 387 Eq. 20-12). 

The biosynthesis of L-cysteine entails the sulfhydryl transfer to an activated form of serine. This pathway to L-cysteine has been most thoroughly studied in E. coli. In the first step an acetyl group is transferred from acetyl-CoA to serine to yield (9-acetylserine (fig. 21.8a). The reaction is catalyzed by serine transacetylase. The formation of cysteine itself is catalyzed by O-acetylserine sulfhydrylase. 

N-Acetyl-L-phenylalanylsarcosine amide, 348 O-Acetylserine, 148 N-0 Acyl migrations, 157 Acyl-enzyme, 342-350 Z-0-Acylisoamide, 295 1,4-Addition, 221-242 1,6-Addition, 231 L-Ala-L-Ala-pNA,350 f-Ala-T-Pro-pNA, 350 AicohoT dehydrogenase, 340-341 Aldehydes, 209-211 Aldol condensation, 304-306 2-Alkoxytetrahydrofuran, 86 2-Alkoxytetrahydropyran, 18, 85-90 Alkylation of enamine, 282 Alkylation of enolate, 280 C and 0-Alkylation, 240 O-Alkylbenzohydroximoyl chloride, 155... 

The serine proteases act by forming and hydrolyzing an ester on a serine residue. This was initially established using the nerve gas diisopropyl fluorophosphate, which inactivates serine proteases as well as acetylcholinesterase. It is a very potent inhibitor (it essentially binds in a 1 1 stoichiometry and thus can be used to titrate the active sites) and is extremely toxic in even low amounts. Careful acid or enzymatic hydrolysis (see Section 9.3.6.) of the inactivated enzyme yielded O-phosphoserine, and the serine was identified as residue 195 in the sequence. Chy-motrypsin acts on the compound cinnamoylimidazole, producing an acyl intermediate called cinnamoyl-enzyme which hydrolyzes slowly. This fact was exploited in an active-site titration (see Section 9.2.5.). Cinnamoyl-CT features a spectrum similar to that of the model compound O-cinnamoylserine, on denaturation of the enzyme in urea the spectrum was identical to that of O-acetylserine. Serine proteases act on both esters and amides. 

When cucurbit cells are fed O-acetylserine or its metabolic precursors the rate of hydrogen sulfide emission in response to sulfate declines, and the incorporation of labeled sulfur from 35S-sulfate into cysteine increases (18). Inhibition of the synthesis of the O-acetylserine precursor acetyl coenzyme A by 3-fluoropyruvate (22) enhances hydrogen sulfide emission, but inhibits cysteine synthesis (1 ). These observations indicate that the availability of O-acetylserine is the rate limiting factor in cysteine synthesis. Hydrogen sulfide may be emitted to the extent the amount of sulfate reduced exceeds the synthesis of O-acetylserine. Therefore, direct release of sulfide from carrier-bound sulfide appears to be responsible for the emission of hydrogen sulfide in response to sulfate (Figure 1, pathway 1). 

Figure 3.1. The biosynthesis of azidoalanine (8) from inorganic azide and O-acetylserine in S.

Beta replacement is catalyzed by such enzymes of amino acid bios5mthesis as tryptophan synthase (Chapter 25), O-acetylserine sulfhydrylase (cysteine synihase), and cystathionine 3-synthase (Chapter In both elimination and (I replace-... 

S. L. (2005) The active site of O-acetylserine sulfhydrylase is the anchor point for bienzyme complex formation with serine acetyl-transferase./. Bacteriol. 187, 3201-3205. 

Cook, P.F., Tai, C.H., Hwang, C.C., Woehl, E.U., Dunn, M.F., and Schnackerz, K.D. (1996) Substitution of pyridoxal 5 -phosphate in the O-acetylserine sulfhydrylase from Salmonella typhimurium by cofactor analogs provides a test of the mechanism proposed for formation of the alpha-aminoacrylate intermediate. J. Biol. Chem. 271, 25842-25849. 

Pyridoxal 5 -phosphate-dependent a, -elimination reactions of O-acetylserine sulfhydrylase 01ACR49. 

Some bacteria link serine to H2S (see here) to make cysteine (Cys). However, plants and most bacteria react / -O-acetylserine with H2S to make cysteine, as shown here. 

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