PROTEIN STRUCTURE 



disulfide linkages per molecule in both species (19) for 65,000 

 molecular weight, or 18 if the molecular weight is taken as 

 69,000 — and the evidence thus suggests that all of these serve 

 to cross-link different segments within a single peptide chain, 

 which must therefore be folded back and forth in many loops. 

 The number of proline residues — 29 for human, 32 for bovine 

 albumin, taking the molecular weight as 65,000 — is ample to 

 provide the necessary turning points for reversal of chain 

 direction in the loops; although we must emphasize again that 

 proline is not necessarily involved. This picture has received 

 further support from the work of McDuffie and Hunter (74), 

 who have reduced all the disulfide groups of human albumin to 

 sulfhydryls with thioglycolate, in the presence of a detergent 

 or of concentrated urea solution, and then blocked the sulf- 

 hydryls with iodoacetamide to prevent reoxidation: 



RSH + CH2I.CONH2 > R.S.CH2.CONH2 



The resulting molecule is insoluble in water but forms a soluble 

 complex with detergents such as dodecyl sulfate ; the composition 

 and molecular weight of the complex indicated that no break- 

 down of the albumin molecule into smaller units had occurred, 

 so that a single peptide chain of about 550 units was apparently 

 present. Thus the general pattern of the albumin molecule 

 appears to be not unlike that suggested above for ribonuclease 

 but on a much larger scale, with a peptide chain more than four 

 times as long as that of ribonuclease, and four times as many 

 disulfide cross links. 



Reichmann and Colvin (88) have oxidized the disulfide sulfur atoms of 

 bovine albumin to sulfonic acid groups with performic acid, and find a decrease 

 of molecular weight, by light scattering and osmotic pressure, to less than half 

 the original value. No increase in free end groups was observed, however. 

 If only disulfide bonds are broken by performic acid oxidation, these results 

 imply that bovine albumin consists of three or four peptide chains, bound 

 together by disulfide bonds. It is possible, however, that other reactions, 

 involving the breakage of peptide chains, may be produced by this reagent. 

 Final judgment as to whether serum albumin consists of one or of several pep- 

 tide chains must therefore be postponed. 



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