Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin I converting enzyme (ACE) and neutral endopeptidase ("enkephalinase"; NEP), were purified to homogeneity from human renal membranes. NEP hydrolyzed substance P (SP) at Gln6-Phe7, Phe7-Phe8, and Gly9-Leu10 and neurotensin (NT) at Pro10-Tyr11 and Tyr11-Ile12. ACE cleaved SP at Phe8-Gly9 and Gly9-Leu10 to release C-terminal tri- and dipeptide (ratio = 4:1). The hydrolysis was dependent on chloride ion and inhibited by captopril. Modification of arginine residues in ACE with cylcohexanedione or butanedione inhibited hydrolysis of SP, bradykinin and Bz-Gly-Phe-Arg (80-93%) indicating an active site arginine is required for hydrolysis of SP. ACE cleaved NT at Tyr11-Ile12 to release Ile12-Leu13. These studies indicate that ACE and NEP, two enzymes which are widely distributed in the body, may be involved in the metabolism of SP and NT.
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PMID:Characterization of the metabolism of substance P and neurotensin by human angiotensin I converting enzyme and "enkephalinase". 241 54

Angiotensin I converting enzyme (kininase II; ACE) has been described as a peptidyldipeptidase or dipeptidyl carboxypeptidase (EC 3.4.15.1) of the pulmonary endothelial cells, which liberates angiotensin II or inactivates kinins. However, ACE has a much wider distribution and substrate specifity; it is concentrated in human epithelial cells (e.g. brush border of the kidney, placenta, intestine and choroid plexus), neuroepithelial cells (subfornical organ, pallidonigral dendrites, median eminence) and male genital tract (testes, prostate, epididymides, seminal plasma). Its substrates include enkaphalins, the C-terminal extended proenkephalins and a protected chemotactic tripeptide. Recent, mostly in vitro studies with purified ACE, indicate that ACE also cleaves peptides by other than peptidyldipeptidase action. Homogeneous human ACE inactivated substance P in spite of its blocked C-terminus (Met11-NH2) primarily by releasing the C-terminal tripeptide. A blocked C-terminal tripeptide, Arg-Pro-Gly-NH2 was also released from the luteinizing hormone releasing hormone (LHRH). Although ACE shares many properties with carboxypeptidases, it surprisingly cleaves the N-terminal tripeptide greater than Glu1-His2-Trp3 from LHRH. Because human ACE hydrolyzes a variety of peptide hormones, actions of its inhibitors may go well beyond blocking the conversion of angiotensin I.
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PMID:The broad substrate specificity of human angiotensin I converting enzyme. 244 Jun 24

Angiotensin I converting enzyme (ACE) and neutral endopeptidase ("enkephalinase"; NEP), were purified to homogeneity from human kidney. NEP cleaved substance P (SP) at Gln6-Phe7,-Phe8, and Gly9-Leu10 and neurotensin (NT) at Pro10-Tyr11 and Tyr11-Ile12. NEP hydrolyzed 0.1 mM SP, NT and their C-terminal fragments at the following rates (mumol/min/mg): SP1-11 = 7.8, SP4-11 = 11.7, SP5-11 = 15.4, SP6-11 = 15.6, SP8-11 = 6.7, NT1-13 = 2.9, and NT8-13 = 4.0. Purified ACE rapidly inactivated SP as measured in bioassay. HPLC analysis showed that ACE cleaved SP at Phe8-Gly9 and Gly9-Leu10 to release C-terminal tri- and dipeptide (ratio = 4:1). The hydrolysis was Cl- dependent and inhibited by captopril. ACE released mainly C-terminal tripeptide from SP methyl ester, but only dipeptide from SP free acid. Modification of arginine residues in ACE with cyclohexanedione or butanedione similarly inhibited hydrolysis of SP, bradykinin and Bz-Gly-Phe-Arg (80-93%) indicating an active site arginine is required for hydrolysis of SP. ACE hydrolyzed NT at Tyr11-Ile12 to release Ile12-Leu13. SP, NT and their derivatives (0.1 mM) were cleaved by ACE at the following rates (mumol/min/mg): SP1-11 = 1.2, SP methyl ester = 0.7, SP free acid = 8.5, SP4-11 = 2.4, SP5-11 = 0.9, SP6-11 = 1.4, SP8-11 = 0, NT1-13 = 0.2, and NT8-13 = 1.3. Peptide substrates were used as inhibitors of ACE (substrate = FA-Phe-Gly-Gly) and NEP (substrate = Leu5-enkephalin).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hydrolysis of substance p and neurotensin by converting enzyme and neutral endopeptidase. 620 35