Cysteine disulfide

After exposure to an oxidant, the potential types of oxidation products in proteins and peptides can be extensive (Stadtman and Fevine, 2000). Cysteine and methionine undergo a variety of sulfur oxidation reactions to yield cysteine disulfides, methionine sulfoxide, methionine... 

Physiologists had postulated for a long time about the existence of a sodium excreting hormone to prevent Na overload and consequent deleterious effects of high blood pressure on the heart and vascular system. At least two such natriuretic factors have been described atrial or A-type and brain or B-type natriuretic factors. Structurally, the natriuretic factors are peptides with a cysteine-cysteine disulfide bridge creating a characteristic loop , this is illustrated by Figure 8.8. 

Cysteine disulfide formation is one of the most important posttranslational modifications involved in protein structure. Disulfides play a crucial role in maintaining the structure of many proteins including insulin, keratin, and many other structurally important proteins. While the cytoplasm and nucleus are reducing microenvironments, the Golgi and other organelles can have oxidizing environments and process proteins to contain disulfide bonds (Scheme 5). 

Protein thermostability may be related to glycosylation and compactness but not cysteine disulfide bonds. 

Calcitonin is a single-chain polypeptide composed of 32 amino acid residues having a molecular weight of approximately 3600. A cysteine disulfide bridge at the 1-7 position of the amino terminal end of the peptide is essential for biological activity however, the entire amino acid sequence is required for optimal activity. 

Methionine Homocitrulline Alloisoleucine Penicillamine-cysteine disulfide... 

Ceftiofiir is absorbed poorly after oral administration but rapidly after intramuscular injection. In all species, ceftiofur was rapidly metabolized to desfuroyl-ceftioftir and fiiroic acid. Desfiiroylceftiofur occurred in the free form in the plasma of treated cattle but was covalently bound to plasma proteins in rats (82). Maximum blood concentrations of ceftiofiir-related residues were achieved within 0.5 and 2 h of dosing. Unmetabolized ceftiofur was generally undetectable in blood within 2-4 h of dosing (83). More than 90% of the administered dose was excreted within 24 h of administration, mostly in urine. Residues in urine and feces were composed primarily of desfiiroylceftiofur and desfiiroylceftiofur cysteine disulfide, with small amounts of unmetabolized ceftiofur. 

FIGURE 3-7 Reversible formation of a disulfide bond by the oxidation of two molecules of cysteine. Disulfide bonds between Cys residues stabilize the structures of many proteins. 

V-iodoacetyl-V -(5-sulfo- l-naphthyl)ethylenediamine (IAEDANS or 1,5-I-AEDANS) is used for fluorescent labeling of electroblotted proteins on blot transfer membranes. Because IAEDANS reacts with free cysteines, disulfides in the sample must first be reduced with dithiothreitol (DTT). Transferred protein bands are visualized under UV light. 

Disulfide bond exchange. Disulfide linkages are important in determining protein tertiary structure. Disulfide bond formation and/or exchange may occur during metal-catalyzed oxidation of the cysteine residue. This may lead to protein aggregation due to the formation of intermo-lecular disulfide bonds. In addition to cysteine disulfide bond formation, cysteine is susceptible to oxidation (Fig. 134) (200) (See also discussion on thiol chemistry earlier in this chapter). 

Fig. 19.2. Amino acid sequence of the enzyme ribonuclease Tj. Cysteine disulfide bridges which cross-link the linear polypeptide chain are indicated by heavy lines [593 a]...

SYNS CYSTEINE DISULFIDE CYSTIN (-)-CYSTINE CYSTINE ACID DICYSTEINE P,P -DITHIODIALANINE GELUCYSTINE OXIDIZED 1-CYSTEINE... 

Q.26.6 Proteins with subunit chains linked by cysteine-cysteine disulfide bonds (RS-SR) can be reduced to sulfhydryl (R-SH HS-R) containing unlinked chains by the addition of 3-mercaptoethanol or dithiothreitol. These reduced proteins will then run independently according to their molecular... 

The individual chains were then broken down into smaller components Acid was used to cleave the polypeptide backbone, performic acid was used to break the cysteine disulfide bonds, and proteolytic enzymes were used to hydrolyze the polypeptide at specific sites on the chain. The reaction products were separated from each other and their sequence determined. 

Captopril (capoten) Captopiil is a potent ACE inhibitor (K -1.7 nM). Given orally, captopril is absorbed rapidly and has a bioavailabihty of -75%. Peak concentrations in plasma occur within an hour, and the drug is cleared with a tj of 2 hours. Most of the drug is eliminated in urine, 40-50% as captopril and the rest as captopril disulfide dimers and captopril-cysteine disulfide. The oral dose of captopril ranges from 6.25 to 150 mg two to three times daily, with 6.25 mg three times daily or 25 mg twice daily being appropriate for the initiation of therapy for heart failure or hypertension, respectively. Most patients should not receive daily doses in excess of 150 mg. Since food reduces the oral bioavailabiUty of captopril by 25-30%, the drug should be given 1 hour before meals. 

---