Meprin is predominantly involved in parathyroid hormone degradation by the microvillar membranes of rat kidney.
Hydrolysis of fragments of the C-terminal and mid-portions of parathyroid hormone (PTH) by a phosphoramidon-insensitive metallo-endopeptidase, previously purified by us from the microvillar membranes of rat kidney, and by the microvillar membranes of rat kidney themselves were investigated using a reverse-phase HPLC, and the amino acid sequences of each produced PTH metabolite were compared after their determination with an automated gas-phase protein sequencer. The results showed that both the purified microvillar endopeptidase and the microvillar membranes of rat kidney limited hydrolyzed human (h) PTH-(39-84) and hPTH-(39-68) mainly at peptide bonds flanked by a hydrophilic amino acid residue, where are characteristic for the purified microvillar endopeptidase but not for other known endopeptidase including endopeptidase 24.11. In addition, most of PTH metabolites generated by the microvillar membranes were insensitive to phosphoramidon and had amino acid sequences identical to those generated by the purified microvillar endopeptidase, indicating that these metabolites were produced by the enzyme integrated in the membranes. Since analysis of the N-terminal amino acid sequence of the purified microvillar endopeptidase revealed that it was structurally identical to rat meprin (EC 3.4.24.18), these results indicate that the purified microvillar endopeptidase or meprin is predominantly involved in PTH degradation by the microvillar membranes of rat kidney as an integral membrane protein.
Yamaguchi
T
T
Department of Medicine, Kobe University School of Medicine, Japan.
Fukase
M
M
Kido
H
H
Sugimoto
T
T
Katunuma
N
N
Chihara
K
K
D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D007668:Kidney / Q000201:enzymology* / Q000648:ultrastructure; D008666:Metalloendopeptidases / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D008871:Microvilli / Q000201:enzymology; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000032:analysis / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism; D051381:Rats
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D008666:Metalloendopeptidases; C053833:meprin A