Comparison of Human Normal, Full-Term, Fetal and Adult Plasminogen by Physical and Chemical Analyses

Abstract

Human fetal plasminogen was isolated from fetal cord blood obtained from full-term normal newborns. Two fetal plasminogen preparations were characterized by physical analyses and compared to adult human Glu-plasminogen. The protein concentration of plasminogen in each full-term fetal plasma was approximately 50% of the concentration found in adult plasma. The specific activity of the isolated plasminogen from both full-term fetal plasmas was 28.8 ± 1.5 IU/mg protein, approximately the same as that of adult Glu-plasminogen. No significant difference was observed in the rate at which plasmin was generated from the normal fetal plasminogen and the adult Glu-plasminogen using streptokinase, urokinase, and tissue plasminogen activator. Electrophoretic analyses in an acrylamide gel/sodium dodecyl sulfate dissociating system showed that the fetal plasminogens and the adult Glu-plasminogen were the same molecular size. Analyses in an acrylamide gel isoelectric focusing system indicated that fetal and adult plasminogen both contained the same twelve isoelectric forms, however, there was a slight difference in the distribution of the isoelectric forms. The fetal and adult plasminogens both contained 792 ± 1 amino acid residues, and there were no significant differences in amino acid composition between the fetal and adult preparations. These comparisons indicate that normal, full-term, fetal and adult Glu-plasminogen are identical.

Neonatal plasminogen displays altered cell surface binding and activation kinetics. Correlation with increased glycosylation of the protein.

“…These high values for both Km and k,,t may indicate that the transition state of neonatal plasminogen 2 is unstable: the high Km reflects the decreased probability of the molecule reaching the transition state, and the kept reflects the instability of the transition state as the plasminogen is converted to plasmin. Our data differ from those of Summaria (37), who showed similar activation for neonatal and adult plasminogen. However, because these studies used plasminogen from only two neonates, relative to the 60 in this study, it is likely that our data more closely reflect the neonatal plasminogen population.…”

“…Adult and neonatal plasminogen and plasmin exhibited similar migration on SDS-PAGE, respectively, providing evidence of the similarity between the adult and neonatal molecules. In addition, amino acid composition of the plasminogen glycoforms is virtually identical, as has been noted in a previous study by Summaria (37). Moreover, the amino acid sequences of neonatal and adult plasminogen glycoforms appear to be identical.…”

“…The increased sialic acid content is consistent with our observations of a much more acidic migration of the neonatal plasminogen by isoelectric focusing gels. An earlier study using plasminogen isolated from two full-term newborns showed little difference in migration between the neonatal and adult plasminogens (37). However, in these studies the two glycoforms were not separated, nor was carbohydrate analysis performed.…”

Microparticle-enhanced nephelometric immunoassay of human plasminogen

“…This range of calibration allows the determination of normal range of hPIg concentrations in 130 adult plasma (mean = 101 mg/L, k 2 SD range = 54-1 48 m a ) , and covers published values for healthy adults (means between 100 and 120 mg/L), new boms (about 50% lower), and pathological increased or decreased levels associated with hereditary disorders, inflammation, and hepatitis (29)(30)(31)(32)(33). Moreover, the risk of analyte underevaluation in Table 1.…”

Bleeding and Thrombosis Issues in Pediatric Patients: Current Approach to Diagnosis and Treatment

“…Furthermore, the capacity of newborns to generate thrombin, dependent upon plasma concentrations of procoagulants, is reduced [5,6] . These facts, theoretically increasing the risk of severe bleeding, are balanced by the protective effects of physiological defi ciencies of the inhibitors of coagulation, as well as by the decreased fi brinolytic capacity in infants [4,7] .…”