title: The renal handling of pepsinogen A isozymogens in man.
abstract: Pepsinogen A (PGA) isozymogens are low molecular weight proteins that are present in serum and urine. The differences in the molecular structure of PGA-isozymogens involve only 2-4 amino acid substitutions. In a previous study, performed in 13 subjects only, a remarkable difference between the fractional renal clearances of the main PGA-isozymogens (PGA-3, PGA-4 and PGA-5) has been demonstrated. The aim of the present study was to further investigate these differences in fractional clearance between PGA-isozymogens and to determine whether these differences are caused by differences in glomerular sieving. For this purpose the fractional clearances of PGA-isozymogens were measured in 57 subjects. In accordance with the previous study, the median fractional clearance of PGA-5 (13%) was lower than the median fractional clearance of PGA-4 (17%; p < 0.02) and the median fractional clearance of PGA-4 was lower than the median fractional clearance of PGA-3 (26%; p < 0.001). The glomerular sieving coefficients of PGA-isozymogens were measured in 11 subjects during an elective heart catheterization by means of the fractional renal extraction method. No significant difference between the glomerular sieving coefficients of PGA-isozymogens could be demonstrated, being 0.81 for PGA-3, 0.96 for PGA-4 and 0.84 for PGA-5. It is concluded that the differences in renal handling between PGA-isozymogens must be explained by differences in tubular reabsorption. These differences in tubular reabsorption between PGA-isozymogens support the hypothesis that positively charged amino acid residues of proteins are involved in the tubular protein reabsorption.
authors.affiliation: Department of Internal Medicine, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Zwiers
authors.forename: M A
authors.initials: MA
authors.lastname: ten Dam
authors.forename: J B
authors.initials: JB
authors.lastname: Crusius
authors.forename: C J
authors.initials: CJ
authors.lastname: Werter
authors.forename: G
authors.initials: G
authors.lastname: Pals
authors.forename: A J
authors.initials: AJ
authors.lastname: Donker
authors.forename: S G
authors.initials: SG
authors.lastname: Meuwissen
authors.forename: R W
authors.initials: RW
authors.lastname: ten Kate
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010435:Pepsinogens / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D010435:Pepsinogens