Sulfhydryl group coenzyme

All the individual steps are catalyzed by enzymes NAD" (Section 15 11) is required as an oxidizing agent and coenzyme A (Figure 26 16) is the acetyl group acceptor Coen zyme A is a thiol its chain terminates m a sulfhydryl (—SH) group Acetylation of the sulfhydryl group of coenzyme A gives acetyl coenzyme A... 

We can descnbe the major elements of fatty acid biosynthesis by considering the for mation of butanoic acid from two molecules of acetyl coenzyme A The machinery responsible for accomplishing this conversion is a complex of enzymes known as fatty acid synthetase Certain portions of this complex referred to as acyl carrier protein (ACP), bear a side chain that is structurally similar to coenzyme A An important early step m fatty acid biosynthesis is the transfer of the acetyl group from a molecule of acetyl coenzyme A to the sulfhydryl group of acyl carrier protein... 

An acyl-transfer and redox coenzyme containing two sulfhydryl groups that form a dithiolane ring in the oxidized (disulfide) form. The redox potential at pH 7 is -0.29 volts. Lipoic acid is attached to the e-amino group of lysyl residues of transacetylases (subunit of a-ketoacid dehydrogenase complexes), thereby permitting acyl... 

Arsenic can react Irreversibly with the critical sulfhydryl groups of the coenzyme Tipolc acid, which Inactivates the coenzyme and thus Inhibits the PDH complex and the a-ketoglutarate dehydrogenase complex. 

Figure 8-2. Pathway for synthesis of palmitate by the fatty acid synthase (FAS) complex. Schematic representation of a single cycle adding two carbons to the growing acyl chain. Formation of the initial acetyl thioester with a cysteine residue of the enzyme preceded the first step shown. Acyl carrier protein (ACP) is a component of the FAS complex that carries the malonate covalently attached to a sulfhydryl group on its phosphopantatheine coenzyme (-SH in the scheme).

Regeneration of reduced enzyme In order for ribonucleotide reductase to continue to produce deoxyribonucleotides, the disulfide bond created during the production of the 2 -deoxy carbon must be reduced. The source of the reducing equivalents is thioredoxin—a peptide coenzyme of ribonucleotide reductase. Thioredoxin contains two cysteine residues separated by two amino acids in the peptide chain. The two sulfhydryl groups of thioredoxin donate their hydrogen atoms to ribonucleotide reductase, in the process forming a disulfide bond (see p. 19). 

Examination of the three-dimensional structure of papain (Lab Quip) indicated that because of the extended groove present in the vicinity of the active site residue Cys-25, it should be feasible to alkylate the sulfhydryl group with a coenzyme analog, still permitting the binding of potential substrates. 

However, this reaction is in fact the sum of five reactions catalyzed by three enzymes and requiring five cofactors coenzyme A (CoA), NAD+, FAD, thiamine pyrophosphate (TPP), and lipoic acid (an 8-carbon acid with sulfhydryl groups at positions 6 and 8). The detailed steps of these reactions are shown in Fig. 12-7. 

Let us consider the mechanism of glyceraldehyde 3-phosphate dehydrogenase in detail (Figure 16.8). In step 1, the aldehyde substrate reacts with the sulfhydryl group of cysteine 149 on the enzyme to form a hemithioacetal. Step 2 is the transfer of a hydride ion to a molecule of NAD + that is tightly bound to the enzyme and is adjacent to the cysteine residue. This reaction is favored by the deprotonation of the hemithioacetal by histidine 176. The products of this reaction are the reduced coenzyme NADH and a thioester intermediate. This thioester intermediate has a free energy close to that of the reactants. In step 3, orthophosphate attacks the thioester to form 1,3-BPG and free the cysteine residue. This displacement occurs only after the NADH formed from the aldehyde oxidation has left the enzyme and been replaced by a second NAD+. The positive charge on the NAD+ may help polarize the thioester intermediate to facilitate the attack by orthophosphate. 

Intermediates in fatty acid synthesis are covalently linked to the sulfhydryl groups of an acyl carrier protein (ACP), whereas intermediates in fatty acid breakdovm are covalently attached to the sulfhydryl group of coenzyme A. 

The thiol ester linkage has been mentioned at various points in this text, most frequently in the material on energy metabolism. This bond occurs when a carboxylic acid is conjugated with a sulfhydryl group, such as the one on coenzyme A. The thiol ester linkage is an important concern to those studying the mechanisms of action of acetyi-CoA carboxylase, citrate synthase, piopionyl-CoA carboxylase, and HMG-CoA synthase. 

The final step in fatt acid synthesis is the dischar ge of the fatty acid from the sulfhydryl group of fatty acid synthase. This discharge involves the attack of a molecule of coenzyme A, resulting in the release of the fatly acid as fatty acyl-CoA, as shown in Figure 5.14. 

Important thiols (sulfhydryls) of the cell, such as the sulfhydryl groups of proteins and coenzyme A, are maintained in the reduced form by thioltransferase... 

Coenzyme A (CoASH) contains a sulfhydryl group that reacts with carboxylic acids to form thioesters such as acetyl CoA, succinyl CoA, and palmitoyl CoA (Figure 4-7). 

Coenzyme A. The terminal sulfhydryl group is the reactive group of the molecule. 

Acetylation is a very common metabolic reaction, which occurs with amino, hydroxyl or sulfhydryl groups. The acetyl group is transferred from acetyl-Coenzyme A, and the reaction is catalyzed by acetyltransferases. An important aspect of this kind of substitution is the genetic polymorphism of one acetyltrans-ferase in humans, who are divided into fast and slow acetyla-tors. In a few cases, the conjugates are further metabolized to toxic compounds, as is seen with isoniazid. Some evidence exists that acetylation of the antitubercular isoniazid leads to enhanced hepatotoxicity of the drug. " Acetylation followed by hydrolysis and CYP-dependent oxidation yields free acetyl... 

Pantothenic acid is needed for coenzyme A (CoA) (Fig. 7.17). Deficiencies of CoA are not known. It is a widespread coenzyme which serves as a carrier of acyl groups (acetyl-CoA) by linking acetyl to the sulfhydryl group of CoA. 

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