Effect of desialylation of human chorionic gonadotropin on its metabolic clearance rate in humans.

We determined the MCR and other kinetic parameters of desialylated hCG (as-hCG) in eight subjects (four men and four women), aged 20-47, using a single injection of 1 mg of a highly purified preparation. The plasma disappearance curve was fitted to a single exponential equation, with a half-time of disappearance of 3.56 +/- 0.62 min (mean +/- SD) and an initial volume of distribution of 1790 +/- 582 ml/m2. The mean MCR of as-hCG was 349 +/- 96 ml/min X m2. The mean transit time of as-hCG was 373 times shorter than that of hCG. The rapid plasma disappearance of as-hCG could not be accounted for by renal clearance into urine, since less than 0.05% of the as-hCG injected was excreted in the urine, nor could it be explained by degradation by plasma proteases, since as-hCG was not appreciably degraded during incubation in human serum at 37 C for 3 h. These data show that desialylation markedly accelerates the MCR of hCG in the human in spite of reduced renal excretion and, therefore, indicate the presence of a highly active pathway for uptake of desialylated glycoproteins.