Disease relevance of XPNPEP1

• Our results provide evidence that the primary defect conferring ileitis in SAMP mice originates from a nonhematopoietic source [1].
• Quercus ilex L. subsp. ballota (Desf.) Samp., a Mediterranean evergreen species growing in a continental Mediterranean climate, did not experience water stress and showed greater sensitivity to winter stress than to summer stress over a 12-month period [2].
• These results indicate that further work is warranted to determine the effectiveness of SAMP lyase as an indicator of breast and prostatic cancers [3].
• The high activity of adenylosuccinate (SAMP) lyase found in rat breast tumor, and its relative absence from normal rat breast tissue, suggests that it may serve as an indicator for human breast malignancy [3].

High impact information on XPNPEP1

• These mutant proteins lack most of the seven 20-amino-acid repeats and all SAMP motifs that have been associated with down-regulation of intracellular beta-catenin levels [4].
• WT lymphocytes from reconstituted SAMP mice resembled native SAMP populations in regard to surface phenotype and cytokine production [1].
• We used bone marrow chimeras to determine if SAMP ileitis results from a primary immunological defect or from dysregulated mucosal immunity secondary to intrinsic, nonhematopoietic (e.g., epithelial) dysfunction [1].
• Decreased barrier function suggests that defects in the epithelium may represent the primary source of SAMP ileitis susceptibility [1].
• 5-Amino-4-imidazolecarboxamide ribotide (AICAR) and AMP were competitive with SAICAR and SAMP (Ki[AICAR] = 11.3 microM; Ki[AMP] = 9.2 microM), whereas fumarate inhibited noncompetitively (Kii = 2.3 mM, Kis = 2.8 mM) [5].

Biological context of XPNPEP1

• Cloning, chromosomal sublocalization of the human soluble aminopeptidase P gene (XPNPEP1) to 10q25.3 and conservation of the putative proton shuttle and metal ligand binding sites with XPNPEP2 [6].
• A novel human cDNA (XPNPEPL) encoding a protein of 623 amino acids exhibiting 44% sequence identity and 62% sequence similarity to pig kidney X-prolyl aminopeptidase (aminopeptidase P; EC 3.4.11.9) was obtained by reverse transcription/polymerase chain reaction of phytohemagglutinin-stimulated lymphocyte mRNA [7].
• Senescence acceleration-prone (SAMP) mice are a group of inbred strains that provide animal models of aging and of various age-related disease processes in the brain and peripheral tissues [8].
• For the second intermediate 4 the asymmetric alpha-alkylation of an O-protected derivative of 4-hydroxybutanal was performed exploiting the SAMP/RAMP hydrazone alkylation methodology, and followed by a highly Z-selective Horner-Wadsworth-Emmons reaction under modified conditions [9].
• Recent studies revealed that SAMP strains have dysfunctional hyperactive mitochondria and are under a higher oxidative stress status from a young age [10].

Anatomical context of XPNPEP1

• Cytosolic aminopeptidase P was obtained in highly purified form from human leukocytes by a four-step procedure [11].

Associations of XPNPEP1 with chemical compounds

• The competitive inhibition by AICAR and AMP suggests a single active site that binds both SAICAR and SAMP [5].
• The kcat for adenylosuccinate (SAMP) cleavage was 97 s-1 with a Km of 1.79 microM [5].
• The key steps generating the stereogenic centers rely on the asymmetric alpha-alkylation of aldehydes or ketones exploiting the SAMP/RAMP hydrazone alkylation methodology, as well as an enzymatic enantioselective reduction of a 3,5-dioxocarboxylate [12].
• The key step of establishing the chiral center was achieved through stereoselective alkylation with benzyl chloromethyl ether using Enders' RAMP/SAMP chiral auxiliary method [13].
• Work using classical paper chromatographic techniques for detecting free amino acids indicated that the octapeptide, des-(Arg9)-bradykinin, enters these cells and its amino-terminal arginine residue is released by cytosolic aminopeptidase-P [14].

Other interactions of XPNPEP1

• The translocation disrupts XPNPEP2, which encodes an Xaa-Pro aminopeptidase that hydrolyzes N-terminal Xaa-Pro bonds [15].
• Whole blood, plasma Mn levels and expression of MnSOD and cAP-P did not differ between the groups [16].

Analytical, diagnostic and therapeutic context of XPNPEP1

• Northern blot analysis indicates an ubiquitous expression of the human XPNPEPL sequence [7].
• Isolation and sequence analysis of a human cDNA clone (XPNPEPL) homologous to X-prolyl aminopeptidase (aminopeptidase P) [7].
• Plasminogen activator inhibitor-1 (PAI-1) antigen levels were significantly higher in SAFP compared with SAMP (18.2 vs. 13.3 U/ml, P = 0.04) even after adjustment for known covariates, but there was no difference in PAI-1 antigen levels between males and females in the control group [17].

References