POSTTRANSLATIONAL MODIFICATION OF TRANSTHYRETIN IN PLASMA

To determine the behavior of transthyretin (TTR) in blood circulation, TTR purified from normal subjects' plasma was injected to rats, and b lood and urine were collected time dependently. Although TTR in plasma was proven to be a predominantly cysteine (Cys) conjugated form by el ectrospray ionization mass spectrometry (ESI-MS) analysis, it was grad ually converted into free, 32 Da (dihydroxylation), 80 Da (phosphoryla tion), and 306 Da (glutathionylation), increased forms in molecular we ight of TTR. The plasma levels of TTR were decreased in a time-depende nt manner with the half life of 72.4 min. No secretion of TTR into the urine was observed by ESI-MS. In conclusion, this method can be simpl y performed without loading a radioactive molecule to the targeted pro tein. It offers a possibility to determine natural protein behaviors i n the bloodstream. (C) 1998 Academic Press.