Cysteine acetylation

Acetic anhydride Acetaminophen Acetazolamide Acetrizoate sodium Acetyl cysteine Acetyl sulfisoxazole Afloqualone... 

Five biogenic thiols (/-cysteine, acetyl-/-cysteine, mercaptoacetic acid, y-gluta-mylcysteine, glutathione) were isolated from water, derivatized wifli 7-fluorobenzo-2-oxa-l,3-diazole-4-sulfonate (SBD-F), and analyzed on a C]g column (A = 385 nm, ex 515 nm, em). A complex 40-min 90/10 0/100 water (0.1% TFA)/acetonitrile... 

The final step in the /3-oxidation cycle is the cleavage of the /3-ketoacyI-CoA. This reaction, catalyzed by thiolase (also known as j8-ketothiolase), involves the attack of a cysteine thiolate from the enzyme on the /3-carbonyI carbon, followed by cleavage to give the etiolate of acetyl-CoA and an enzyme-thioester intermediate (Figure 24.17). Subsequent attack by the thiol group of a second CoA and departure of the cysteine thiolate yields a new (shorter) acyl-CoA. If the reaction in Figure 24.17 is read in reverse, it is easy to see that it is a Claisen condensation—an attack of the etiolate anion of acetyl-CoA on a thioester. Despite the formation of a second thioester, this reaction has a very favorable A).q, and it drives the three previous reactions of /3-oxidation. 

FIGURE 24.17 The mechanism of the thiolase reaction. Attack by an enzyme cysteine thiolate group at the /3-carbonyl carbon produces a tetrahedral intermediate, which decomposes with departure of acetyl-CoA, leaving an enzyme thioester intermediate. Attack by the thiol group of a second CoA yields a new (shortened) acyl-CoA. 

Therapeutic Function Expectorant Chemical Name N-acetyl-L-cysteine Common Name —... 

Step 1 of Figure 27.7 Claisen Condensation The first step in mevalonate biosynthesis is a Claisen condensation (Section 23.7) to yield acetoacetyl CoA, a reaction catalyzed by acetoacetyl-CoA acetyltransferase. An acetyl group is first bound to the enzyme by a nucleophilic acyl substitution reaction with a cysteine —SH group. Formation of an enolate ion from a second molecule of acetyl CoA, followed by Claisen condensation, then yields the product. 

The retro-Claisen reaction occurs by initial nucleophilic addition of a cysteine -SH group on the enzyme to the keto group of the /3-ketoacyl CoA to yield an alkoxide ion intermediate. Cleavage of the C2-C3 bond then follows, with expulsion of an acetyl CoA enolate ion. Protonation of the enolate ion gives acetyl CoA, and the enzyme-bound acyl group undergoes nucleophilic acyl substitution by reaction with a molecule of coenzyme A. The chain-shortened acyl CoA that results then enters another round of tire /3-oxidation pathway for further degradation. 

Step 2, another priming reaction, involves a further exchange of thioester linkages by another nucleophilic acyl substitution and results in covalent bonding of the acetyl group to a cysteine residue in the synthase complex that will catalyze the upcoming condensation step. 

All of the carbons of glycine, serine, alanine, and cysteine and two carbons of threonine form pyruvate and subsequently acetyl-CoA. 

Bimer G, Vamvakas S, Dekant W, et al. 1993. Nephrotoxic and genotoxic N-acetyl-S-dichlorovinyl-L-cysteine is a urinary metabolite after occupational 1,1,2-trichloroethene exposure in humans Implications for the risk of trichloroethene exposure. Environ Health Perspect 99 281-284. 

Commandeur JNM, Vermeulen NPE. 1990a. Identification of N-acetyl-S-(2,2-dichlorovinyl) and N-acetyl-S-(l,2-dichlorovinyl)-L-cysteine as two regioisomeric mercapturic acids of trichloroethylene in the rat. Chem Res Toxicol 3 212-218. 

Dekant W, Metzler M, Henschler D. 1986a. Identification of S-l,2-dichlorovinyl- N-acetyl-cysteine as a urinary metabolite of trichloroethylene A possible explanation for its nephrocarcinogenicity in male rats. Biochem Pharmacol 35 2455-2458. 

Paracetamol-induced hepatotoxicity can be prevented in animals with SOD, catalase and allopurinol (Kyle et al., 1987 Jaeschke, 1990 Tirmenstein and Nelson, 1990), and by N-acetyl-L-cysteine or methionine in humans (Meredith et al., 1986 Nelson, 1990). The protective efiect of allopurinol in mice only occurred at high concentrations, suggesting that its effect was related to scavenging of ROMs rather than inhibition of their production by XO (Jaeschke, 1990). 

Simon, L.M. and Suttorp, N. (1983). Lung cell oxidant injury decrease in polymorphonuclear leucocyte mediated cytotoxicity by N-acetyl cysteine. Am. Rev. Resp. Dis. 127, 286. 

Eskinja, M., Lamprecht, G., Scherer, G., and Schmid, E. R., Assay of S-ethyl-N-acetyl-L-cysteine in urine by high-performance liquid chromatography using post-column reaction detection, /. Chromatogr. B, 704, 159, 1997. 

L-alanylglycyl-L-cysteinyl-L-lysyl-L-asparaginyl-L-phenylalanyl-L-phenylalanyl-L-tryptophanyl-L-lysyl-L-threonyl-L-threonyl-L-cysteine 6-0-benzoyl-N-(benzyloxycarbonyl) methylamide 4,6-0-benzylidene-N-benzylidene-N-(benzyloxycarbonyl) methylamide N- (benzyloxy carbonyl) -N-(benzyloxycarbonyl)-, amide N-(benzyloxycarbonyl)-, hydrazide N-(benzyloxycarbonyl)-, methylamide N-(benzyloxycarbonyl)-, methyl ester N-(benzyloxycarbonyl)-L-alanyl-L-alanine methyl ester N-(benzyloxycarbonyl)-L-alanylglycine ethyl ester N-(benzyloxycarbonyl)glycyl-L-alanine methyl ester 3,4,6-tri-0-acetyl-2-amino-2-deoxy-N-(benzyloxycarbonyl)-, benzyl ester, hydrochloride... 

The crystal structure of a CODH/ACS enzyme was reported only in 2002.43,44 It reveals a trio of Fe, Ni, and Cu at the active site (6). The Cu is linked to the Ni atom through two cysteine-S, the Ni being square planar with two terminal amide ligands. Planarity and amide coordination bear some resemblance to the Ni porphinoid in MCR. A two-metal ion mechanism is likely for acetyl CoA synthesis, in which a Ni-bound methyl group attacks an adjacent Cu—CO fragment with formation of a Cu-acyl intermediate. A methylnickel species in CODH/ACS has been identified by resonance Raman spectroscopy.45... 

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