Thiolytic cleavage

Scheme 2 Drug-PEG conjugate via a benzyl carbamate linkage and its thiolytic cleavage...

Klehr argued against this thiolytic cleavage of sulfenamides, as he did not observe accelerated aniline formation from Ph—NH—SR in the presence of 1-thioglycerol24,38. However,... 

These data, e.g. predominant thiolytic cleavage of the semimercaptal at physiological GSH concentrations, is in line with the expected behavior in considering the positive Hammett constant of the sulfonamide substituent (op = +0.5855). It is to be expected that cells with lowered GSH content or impaired enzymic capacity to reduce GSSG will be... 

McGraw, G.W., Steynberg, J.P., and Hemingway, R.W., Condensed tannins a novel rearrangement of procyanidins and prodelphinidins in thiolytic cleavage. Tetrahedron Lett., 34, 987, 1993. 

In peroxisomes, membrane-enclosed organelles of animal and plant cells, the intermediates for /3 oxidation of fatty acids are coenzyme A derivatives, and the process consists of four steps, as in mitochondrial /3 oxidation (Fig. 17-13) (1) dehydrogenation, (2) addition of water to the resulting double bond, (3) oxidation of the /3-hydroxyacyl-CoA to a ketone, and (4) thiolytic cleavage by coenzyme A (The identical reactions also occur in glyoxysomes, as discussed below.)... 

Another related reaction that goes through a ketimine is the conversion of the amino acid kynurenine to alanine and anthranilic add.225 It presumably depends upon hydration of the carbonyl group prior to P cleavage (Eq. 14-35). An analogous thiolytic cleavage utilizes CoA to convert 2-amino-4-ketopentanoate to acetyl-CoA and alanine.226... 

At the end of this sequence, the P-oxoacyl-CoA derivative is cleaved (Fig. 17-1, step e) by a thiolase (see also Eq. 13-35). One of the products is acetyl-CoA, which can be catabolized to C02 through the citric acid cycle. The other product of the thiolytic cleavage is an acyl-CoA derivative that is two carbon atoms shorter than the original acyl-CoA. This molecule is recycled through the P oxidation process, a two-carbon acetyl unit being removed as acetyl-CoA during each turn of the cycle (Fig. 17-1). The process continues until the fatty acid chain is completely degraded. 

The final step in the removal of two carbons from the fatty acid is the thiolytic cleavage to release acetyl-CoA. The term thiolytic refers to the use of Coenzyme A to bond with the carbonyl carbon of the P-keto acid. 

The preceding reactions have oxidized the methylene group at C-3 to a keto group. The final step is the cleavage of 3-ketoacyl CoA by the thiol group of a second molecule of CoA, which yields acetyl CoA and an acyl CoA shortened by two carbon atoms. This thiolytic cleavage is catalyzed by -ketothiolase. 

Figure 19.11. A redox-triggered PEG containing lipid (24) and its thiolytic cleavage.

Ketoacyl-CoA thiolase (/6-ketothiolase) catalyzes a thiolytic cleavage, has broad specificity, and yields acetyl-CoA and acyl-CoA shortened by two carbon atoms. The reaction is highly exergonic... 

In this reaction, sometimes called a thiolytic cleavage, an acetyl-CoA molecule is released. The other product, an acyl-CoA, now contains two fewer C atoms. 

Zn(SH)(Tp Bu>Me)] does not react with esters, phosphates, or CO2, e.g., for thiolytic cleavage reactions, whereas acidic organic X-OH compounds (carboxylic acids, trinitrophenol, hexafluoroacetylace-tone) replace the SH groups with the formation of [Zn(OX)-(Tp Bu Me)].103 The reaction of [Zn(OH)(Tp,Bu Me)] with alcohols has been followed by combined experimental and computational investigations in order to determine the factors influencing the formation of tetrahedral alkoxide complexes. The [Zn(OR)(Tp Bu,Me)l derivatives have been found unstable toward hydrolysis.104... 

Conjugation of the carboxylic group in cholic acid involves participation of a cholic acid CoA ligase and a cholyl-CoA glycine (taurine) acyltransferase [153-158]. Since the primary product of the thiolytic cleavage of the CoA ester of 3a,7a,12a-tri-hydroxy-24-oxo-5/8-cholestanoic acid is the CoA ester of cholic acid, it is probable that only the transferase may be involved in the primary formation of cholic acid in the liver. A description of the properties of the CoA synthetase and the transferase is given in Chapter 11. 

The products of the reaction are acetyl-CoA and an acyl-CoA shortened by two carbon atoms. The equilibrium of the reaction is more to the side of the thiolytic cleavage products thereby driving P-oxidation to completion. All thiolases that have been studied in detail contain an essential sulfhydryl group, which participates directly in the carbon-carbon bond cleavage as outlined in the following equations where E-SH represents thiolase [4]. 

Inside of the mitochondrion, fatty acyl-CoAs are oxidized in a series of steps that each release a two-carbon fragment, in the form of acetyl-CoA. Each step involves four reactions-dehydrogenation, hydration, dehydrogenation, and thiolytic cleavage (Figure 18.16). The individual reactions are summarized as follows ... 

Propionyl-CoA is produced as an intermediate of odd chain fatty acid oxidation. Propionyl-CoA is produced by thiolytic cleavage of the five-carbon homolog of acetoacetyl-CoA (see here). 

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