Renal tubular uptake of protein: effect of molecular charge.
The effect of molecular charge of proteins on proximal tubular reabsorption was evaluated in the rat. Native and two cationized forms of albumin, native and anionized lysozyme, and native and anionized cytochrome c were iodinated with 125I. The different forms of each type of protein were alternately microinfused into the same site of proximal convoluted tubules in vivo. Tubular reabsorption was determined as the difference between the amounts of TCA-precipitable radioactivity infused and recovered in the urine. At low concentration of albumin 5 times more cationized than anionic albumin and 2.7 times more cationic than anionized lysozyme were reabsorbed by the proximal tubule. At two of four concentrations, proximal tubular uptake of cationic cytochrome c exceeded that of anionized cytochrome c. Uptake of cationic cytochrome c exceeded that of cationic lysozyme; however, the difference in uptake between native cationic and anionized species of the two proteins was much greater for lysozyme than for cytochrome c. The data reveal that a higher isoelectric point significantly enhances proximal tubular reabsorption of albumin, lysozyme, and cytochrome c and that proteins with similar molecular weight and isoelectric point are not necessarily reabsorbed to the same degree. This suggests that in addition to total molecular charge the molecular configuration and/or distribution of electrical charges on teh protein surface determine protein binding by the luminal membrane and subsequent endocytosis by the proximal tubule.
D000818:Animals; D001692:Biological Transport; D003574:Cytochrome c Group / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009113:Muramidase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000378:metabolism
D003574:Cytochrome c Group; D011506:Proteins; D012710:Serum Albumin, Bovine; D009113:Muramidase