Analysis of active renin heterogeneity.
Active renin is a heterogeneous enzyme that can be separated into multiple forms with high-resolution isoelectric focusing. The isoelectric heterogeneity may result from differences in glycosylation between the different forms. In order to determine the relationship between active renin heterogeneity and differences in composition or attachment of oligosaccharides, two separate experiments were performed: (i) Tunicamycin, which interferes with normal glycosylation processing, increased the proportion of relatively basic renin forms secreted into the incubation media by rat renal cortical slices. (ii) Endoglycosidase F, which enzymatically removes carbohydrate from some classes of glycoprotein, similarly increased the proportion of relatively basic forms when incubated with active human recombinant renin. In addition, further studies with inhibitors of human renin activity revealed that the heterogeneous renin forms were similarly inhibited by two separate renin inhibitors. These results are consistent with the hypothesis that renin isoelectric heterogeneity is due in part to differences in carbohydrate moiety attachment and that the heterogeneity of renin does not influence access of direct renin inhibitors to the active site of renin.
Katz
S A
SA
Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis 55415.
Malvin
R L
RL
Lee
J
J
Kim
S H
SH
Murray
R D
RD
Opsahl
J A
JA
Abraham
P A
PA
D000818:Animals; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D004151:Dipeptides; D006026:Glycoside Hydrolases / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D007525:Isoelectric Focusing; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D011743:Pyrimidines; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D012083:Renin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology; D000092502:Renin Inhibitors; D009930:Organic Chemicals
D004151:Dipeptides; D006026:Glycoside Hydrolases; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D011743:Pyrimidines; D011994:Recombinant Proteins; D012083:Renin; D014415:Tunicamycin; D000092502:Renin Inhibitors; C070403:EMD 52859; D009930:Organic Chemicals; C070401:EMD 51921