Glycoconjugates as noninvasive probes of intrahepatic metabolism: II. Application to measurement of plasma α 1-acid glycoprotein turnover during inflammation

Abstract

We describe a new method for measuring plasma glycoprotein turnover in vivo using carbohydrate-moiety labeling compared with precursor UDP-sugar monitoring, which allows estimation of the specific activity of the precursor at the biosynthetic site of the glycoprotein. This method has been applied to plasma alpha 1-acid glycoprotein (AGP) kinetics, and has allowed direct quantitation of absolute synthesis rates of AGP in a non-steady state. Following turpentine-induced acute inflammation, AGP was found to undergo a maximum increase in plasma level of eight-fold with a 20- to 25-fold induction in absolute synthesis rate peaking at 25 to 50 h, and a concurrent 2.0 to 2.5-fold increase in fractional degradation rate. The changes in absolute synthesis rates were quite comparable both temporally and quantitatively to changes in hepatic AGP mRNA levels and gene transcription rates reported by others following turpentine inflammation, thus suggesting that AGP synthesis in vivo is predominantly regulated by the level of its mRNA. The carbohydrate moiety labeling method can be applied to other plasma glycoproteins to measure their kinetic parameters in the intact animal or human subject.