Thioesters, oxidation

Now transported to the liver, fatty acids activate Giving CoA thioesters, oxidation is their fate Ketone bodies, Ketone bodies, because low glycerol-P Glucagon up, insulin down, stops reversal to TG. 

Polyhydric alcohol mercaptoalkanoate esters are prepared by reaction of the appropriate alcohols and thioester using -toluenesulfonic acid catalyst under nitrogen and subsequent heating (16,17). Organotin mercapto esters are similarly produced by reaction of the esters with dibutyltin oxide (18). Pentaerythritol can be oxidized to 2,2-bis(hydroxymethyl)hydracryhc acid [2831-90-5] C H qO, ... 

ATP Adenosine triphosphate. Chemical energy generated by substrate oxidations is conserved by formation of high-energy compounds such as adenosine diphosphate (ADP) and adenosine triphosphate (ATP) or compounds containing the thioester bond. 

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. 

Step 1 of Figure 29.3 Introduction of a Double Bond The /3-oxidation pathway begins when a fait)7 acid forms a thioester with coenzyme A to give a fatty acyl Co A. Two hydrogen atoms are then removed from C2 and C3 of the fatty acyl CoA by one of a family of acyl-CoA dehydrogenases to yield an a,/3-unsaturated acyl CoA. This kind of oxidation—the introduction of a conjugated double bond into a carbonyl compound—occurs frequently jn biochemical pathways and usually involves the coenzyme flavin adenine dinucleotide (FAD). Reduced FADH2 is the by-product. 

The four steps of the /3-oxidation pathway, resulting in the cleavage of an acetyl group from the end of the fatty-acid chain. The key chain-shortening step is a retro-Claisen reaction of a /3-keto thioester. Individual steps are explained in the text. 

Step 4 of Figure 29.3 Chain Cleavage Acetyl CoA is split off from the chain in the final step of /3-oxidation, leaving an acyl CoA that is two carbon atoms shorter than the original. The reaction is catalyzed by /3-ketoacyl-CoA thiolase and is mechanistically the reverse of a Claisen condensation reaction (Section 23.7). In the forward direction, a Claisen condensation joins two esters together to form a /3-keto ester product. In the reverse direction, a retro-Claisen reaction splits a /3-keto ester (or /3-keto thioester) apart to form two esters (or two thioesters). 

Step 5 of Figure 29.11 Acyl Transfer Acetyl dihydrolipoamide. a thioester, undergoes a nucleophilic acyl substitution reaction with coen/.yrne A to yield acetyl CoA plus dihydrolipoamide. The dihydrolipoamide is then oxidized back... 

Step 4 of Figure 29.12 Oxidative Decarboxylation The transformation of cr-ketoglutarate to succinyl CoA in step 4 is a multistep process just like the transformation of pyruvate to acetyl CoA that we saw in Figure 29.11. In both cases, an -keto acid loses C02 and is oxidized to a thioester in a series of steps catalyzed by a multienzynie dehydrogenase complex. As in the conversion of pyruvate to acetyl CoA, the reaction involves an initial nucleophilic addition reaction to a-ketoglutarate by thiamin diphosphate vlide, followed by decarboxylation, reaction with lipoamide, elimination of TPP vlide, and finally a transesterification of the dihydrolipoamide thioester with coenzyme A. 

In a synthesis of 2,3-di(hetero)arylpyrido[3,2 [l,4]thiazepines developed by Couture, 2-chloro-3-formylpyridine is reacted with arylmethylamines to form the imines. Deprotonation with LDA at -78 °C followed by treatment with non enolisable aryl thioesters gives the title compounds which may be further annulated by irradiation in benzene in the presence of iodine and propylene oxide <96S986> (Scheme 14). 

Polarographic studies are reported on thioesters, mainly of the type (140) and (141), and on trichloroethylphosphonites. In the field of nucleotides and nucleosides it is found that ATP has a very high surface activity at the mercury electrode, which is strongly dependent upon complex formation with transition metals. The polarographic behaviour of cobalt complexes with triphenylphosphine and its oxide has been studied in order to estimate extraction efficiencies. 

Rovis and co-workers have also shown that pre-catalyst 129 is competent with a wide range of Michael acceptors including oc,P-unsaturated aldehydes, amides, nitriles, esters, thioesters, vinylphosphonates and vinylphosphine oxides (Scheme 12.25) [58,60],... 

To my knowledge, the first transition metal-catalyzed reaction utilizing S-S bond activation was reported by Holmquist el al. in 1960 [14]. The reaction of (PhS)2 with CO (950 atm) in the presence of chromium oxide on AI2O3 at 275°C furnished thioester 57 in 31% yield (Eq. 7.42). 

The process outlined above led to the provision of the necessary quantities of hydrogen for the reduction of CO2, CO, N03 and other oxidized starting materials, which were in turn converted to biomolecules in further reaction steps. The question as to whether contemporary living cells contain relicts, in the form of thioesters or thio compounds, which indicate the great importance of this class of substances, can clearly be answered positively. 

From the oxidative synthesis of thioesters from aldehyde and thiol ... 

In the latter case, electron uptake occurs after decarboxylation of the ketoacid via Fe3+, which is able to take up electrons in strongly oxidized regions of the black-band iron sediments. Fe-ions act catalytically on the process of thioester formation, which can then occur without the help of enzymes. Thus, it was solar UV irradiation which carried the prebiotic thioesters across the energy threshold. 

Cysteine sulfhydryls and cystine disulfides may undergo a variety of reactions, including alkylation to form stable thioether derivatives, acylation to form relatively unstable thioesters, and a number of oxidation and reduction processes (Figure 1.10). Derivatization of the side chain sulfhydryl of cysteine is one of the most important reactions of modification and conjugation techniques for proteins. 

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