Sulfhydryl groups Replacement

Lead (soft, Pb2+) Injuries to peripheral nervous system, disturbs heme synthesis and affects kidneys Pb2+ may replace Ca2+ with loss of functional and structural integrity. Reacts with sulfhydryl groups, replaces Zn2+ in 8-aminolevulinic acid dehydratase. 

Cysteine is derived from serine by replacing the hydroxyl group with the sulfhydryl group. It is the second protein amino acid that contains sulfur. 

The oxidation and reduction steps are coupled through the binding of G3P to a sulfhydryl group on an enzyme that already has bound a NAD+ molecule. The enzyme facilitates a H (hydride ion) shift from G3P to reduce the NAD+ to NADH. The oxidation of G3P results in the formation of a high-energy thioester bond that is subsequently replaced by an orthophosphate group to yield the 1,3-BGP. 

The P. chlororaphis B23 NHase is the ferric enzyme [50], which has been characterized in detail [51,52]. (i) The NHase is the first known nonheme iron enzyme containing a typical low-spin Fe(III) site, (ii) the axial position of the Fe(III) site in the enzyme may be occupied by aquo and sulfhydryl groups, and (iii) aliphatic nitrile substrates directly bind to the Fe(III)-active center through H20-substrate replacement. The NHase also seems to contain pyrroloquinoline quinone (PQQ) or a PQQ-like compound [53]. 

B Elimination has been used to show differences among the disulfide bonds in various proteins including the ovomucoids (54). The e-elimination reaction has also been used to replace the hydroxyl group of the essential serine residue of subtilisin with a sulfhydryl group (55). The thiolsubtilisin had a small fraction of the activity of subtilisin but it has been quite useful in mechanistic studies of the serine and sulfhydryl proteases. 

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. 

The last reaction, oxidation of 1,2,4-triazole-3-thiol to 1,2,4-triazole, requires comment. The replacement of the sulfhydryl group by hydrogen by oxidation with dilute nitric acid was discovered by Marckwald in the imidazole series ... 

Compounds that contain the sulfhydryl group (—SH) are called thiols. They are similar to alcohols in structure, but the sulfur atom replaces the oxygen atom. 

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