Harpers

582 / CHAPTER 50AC+ –Albumin α 1 α 2 β γBD+ –Albumin α 1 α 2 β γFigure 50–2. Technique of cellulose acetate zone electrophoresis. A: A small amount of serum or otherfluid is applied to a cellulose acetate strip. B: Electrophoresis of sample in electrolyte buffer is performed.C: Separated protein bands are visualized in characteristic positions after being stained. D: Densitometerscanning from cellulose acetate strip converts bands to characteristic peaks of albumin, α 1 -globulin, α 2 -globulin,β-globulin, and γ-globulin. (Reproduced, with permission, from Parslow TG et al [editors]: Medical Immunology,10th ed. McGraw-Hill, 2001.)residues from certain plasma proteins (eg, ceruloplasmin)by exposure to neuraminidase can markedlyshorten their half-lives in plasma (Chapter 47).D. MANY PLASMA PROTEINS EXHIBIT POLYMORPHISMA polymorphism is a mendelian or monogenic trait thatexists in the population in at least two phenotypes, neitherof which is rare (ie, neither of which occurs withfrequency of less than 1–2%). The ABO blood groupsubstances (Chapter 52) are the best-known examplesof human polymorphisms. Human plasma proteinsthat exhibit polymorphism include α 1 -antitrypsin, haptoglobin,transferrin, ceruloplasmin, and immunoglobulins.The polymorphic forms of these proteins can bedistinguished by different procedures (eg, various typesof electrophoresis or isoelectric focusing), in which eachform may show a characteristic migration. Analyses ofthese human polymorphisms have proved to be of genetic,anthropologic, and clinical interest.E. EACH PLASMA PROTEIN HAS A CHARACTERISTICHALF-LIFE IN THE CIRCULATIONThe half-life of a plasma protein can be determined bylabeling the isolated pure protein with 131 I under mild,nondenaturing conditions. This isotope unites covalentlywith tyrosine residues in the protein. The labeled proteinis freed of unbound 131 I and its specific activity (disintegrationsper minute per milligram of protein) determined.A known amount of the radioactive protein isthen injected into a normal adult subject, and samples ofblood are taken at various time intervals for determinationsof radioactivity. The values for radioactivity areplotted against time, and the half-life of the protein (thetime for the radioactivity to decline from its peak valueto one-half of its peak value) can be calculated from theresulting graph, discounting the times for the injectedprotein to equilibrate (mix) in the blood and in the extravascularspaces. The half-lives obtained for albuminand haptoglobin in normal healthy adults are approximately20 and 5 days, respectively. In certain diseases,the half-life of a protein may be markedly altered. For instance,in some gastrointestinal diseases such as regionalileitis (Crohn disease), considerable amounts of plasmaproteins, including albumin, may be lost into the bowelthrough the inflamed intestinal mucosa. Patients withthis condition have a protein-losing gastroenteropathy,and the half-life of injected iodinated albumin in thesesubjects may be reduced to as little as 1 day.