Albumin turnover: FcRn-mediated recycling saves as much albumin from degradation as the liver produces.
Algorithms, Animals, Electrophoresis-Polyacrylamide-Gel, Enzyme-Linked-Immunosorbent-Assay, Leucine, Liver, Mice-Inbred-C57BL, Mice-Knockout, Proteins, Receptors-Fc, Research-Support-N, I, H, -Extramural, Research-Support-Non-U, S, -Gov't, Serum-Amyloid-P-Component, Transferrin
Am J Physiol Gastrointest Liver Physiol 2006 Feb; 290(2):G352-60.
It is now understood that the nonclassical major histocompatibility complex-I molecule FcRn binds albumin and retrieves it from an intracellular degradative fate. Whether FcRn in the liver modulates albumin turnover through effects on biosynthesis and production is not known. Thus we quantified the appearance of biosynthetically labeled albumin in plasma after an intravenous bolus injection of [(3)H]leucine in FcRn-deficient mice. The production rates for both albumin (FcRn substrate) and transferrin (nonsubstrate) are increased by approximately 20% in FcRn-deficient mice compared with normal mice, likely compensating for the lowered plasma oncotic pressure caused by hypoalbuminemia in FcRn-deficient mice. Determining the magnitude of FcRn-mediated effects on albumin turnover, we then measured the steady-state plasma concentrations of biosynthetically labeled albumin and transferrin during [(3)H]leucine infusion. The concentration of albumin was approximately 40% lower in FcRn-deficient mice compared with normal mice. Furthermore, the approximately 40% lower plasma albumin concentration in FcRn-deficient mice along with the approximately 20% increase in albumin production indicate, by the mass-balance equation, that albumin degradation in FcRn-deficient mice is twice that of normal mice. These studies of biosynthetically labeled, and thus native, albumin support our previous finding that FcRn protects albumin from degradation. Permitting quantification of the magnitude of FcRn-mediated recycling, they further indicate that FcRn has extraordinary capacity: the amount of albumin saved from degradation by FcRn-mediated recycling is the same as that produced by the liver.
Kim, J; Bronson, C L.; Hayton, W L.; Radmacher, M D.; Roopenian, D C.; Robinson, J M.; and Anderson, C L., "Albumin turnover: FcRn-mediated recycling saves as much albumin from degradation as the liver produces." (2006). Faculty Research 2000 - 2009. 1355.