CHARACTERIZATION OF 2 POSTTRANSLATIONALLY PROCESSED FORMS OF HUMAN SERUM RETINOL-BINDING PROTEIN - ALTERED RATIOS IN CHRONIC-RENAL-FAILURE

Retinol-binding protein (RBP) is the specific blood carrier for the tr ansport of retinol (vitamin A) to target tissues. As the kidney is inv olved in RBP metabolism, the analysis of RBP species in the serum of p atients with chronic renal failure (CRF) was used as a model to study possible RBP alterations. SDS-PAGE-immunoblotting analysis of normal a nd CRF sera shows a doublet of REP bands (band A and band B) near 21 k Da. Mass spectrometric analysis of purified RBPs from CRF and normal s era revealed the presence not only of full-length RBP (183 residues, m igrating in band A) but also two forms of RBP differing from the nativ e form by the loss of C-terminal Leu (i.e., RBP(1) (residues 1-182), m igrating in band A also) and the loss of C-terminal Leu-Leu (i.e., RBP (2) (residues 1-181), migrating in band B). Interestingly, RBP(2) was considerably increased in the serum of CRF, whereas it was low in norm al sera, In healthy retinol target-tissues and in cultured HepG2 cells , RBP(2) levels were significantly and variably present compared to RB P and RBP(1). We propose that these posttranslationally modified forms of RBP occur in cells and that after their release into the blood cir culation RBP(2) is cleared by the kidney in healthy individuals but ac cumulates in the serum of CRF patients. RBP(2) may have an important p hysiological role in retinol transport and/or recycling.