Degradation of porcine relaxin by glutathione-insulin transhydrogenase and a neutral peptidase.
The susceptibility of porcine relaxin and 125I-polytyrosyl-porcine relaxin to degradation by 3 purified enzymes involved in the degradation of insulin and proinsulin was examined. Rat liver glutathione-insulin transhydrogenase (GIT), which cleaves disulfide bonds in insulin, catalyzed a time- and concentration-dependent increase in trichloroacetic acid (TCA)-soluble radioactivity of relaxin. The Sephadex G-50 profile of the reaction products revealed conversion to the A- and B-chains. Relaxin competitively inhibited the degradation of insulin by GIT; however, kinetic analysis revealed insulin to be preferred over relaxin as a substrate. Rat liver cytosol neutral thiol peptidase (NTP) catalyzed a time- and concentration-dependent increase in the TCA solubility of relaxin and a shift in the Sephadex G-50 radioactivity profile to low molecular weight products. Kinetic analysis revealed that insulin and B-chain are preferred over relaxin as substrates for NTP. A third enzyme, rat kidney neutral metalloendopeptidase, which degrades proinsulin and insulin C-peptide but not insulin, also did not degrade porcine relaxin.
D000818:Animals; D001667:Binding, Competitive; D002850:Chromatography, Gel; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008666:Metalloendopeptidases; D008970:Molecular Weight; D015260:Neprilysin; D010088:Oxidoreductases / Q000378:metabolism*; D011490:Protein Disulfide Reductase (Glutathione) / Q000378:metabolism*; D051381:Rats; D012065:Relaxin / Q000378:metabolism*; D013379:Substrate Specificity
D007328:Insulin; D012065:Relaxin; D010088:Oxidoreductases; D011490:Protein Disulfide Reductase (Glutathione); D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D008666:Metalloendopeptidases; D015260:Neprilysin