Conversion of substance P to C-terminal fragments in human plasma.
Substance P is rapidly converted by enzyme(s) in human plasma to des-[Arg1Pro2]-substance P (fragment 3-11) and to des-[Arg1Pro2Lys3Pro4]-substance P (fragment 5-11). These metabolites were isolated by HPLC and partially sequenced. No evidence was obtained for deamidation of substance P in plasma or for the formation of the N-terminal tetrapeptide [Arg-Pro-Lys-Pro]. The data suggest that substance P is metabolized in human plasma by an enzyme with the specificity of dipeptidyl-aminopeptidase IV. Consistent with this hypothesis, the rate of degradation of substance P measured with an antibody directed against the N-terminal region is 2-3-fold greater than measured with a C-terminally directed antibody. The degrading activity of plasma was purified 522-fold and was eluted from a gel filtration column in the molecular weight zone 150 000-170 000 and from a chromatofocusing column in the pH range 4.5 to 5.5.
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000097:blood*; D010450:Endopeptidases / Q000097:blood*; D006801:Humans; D007525:Isoelectric Focusing; D008970:Molecular Weight; D010446:Peptide Fragments / Q000378:metabolism*; D011863:Radioimmunoassay; D013373:Substance P / Q000378:metabolism*
D010446:Peptide Fragments; D013373:Substance P; C031661:substance P (5-11); C038417:substance P (3-11); D010450:Endopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases