Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peptidylglycine alpha-amidating monooxygenase (PAM) is a regulating enzyme to synthesize the biologically active hormones having carboxy-terminal amide. In the present study we investigated secretion of the enzyme from rat saliva. Property of PAM in the saliva was similar to that in the submandibular gland. Both enzymes showed similar pH optimum at 5.0 and optimal ascorbic acid concentration at 2.5 mM. But molecular size of PAM in the saliva was 75 kDa in the gel permeation chromatography on Superose 12 column, while the size in the submandibular gland was 25 kDa. After the treatment with trypsin, PAM in the saliva was converted to a small size molecule, which is similar to the size in rat submandibular gland. These and other data indicate that a native molecular size of PAM is secreted into saliva and plays some physiological roles.
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PMID:Secretion of peptidylglycine alpha-amidating monooxygenase (PAM) from rat salivary glands. 130 47

Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is a granule-associated enzyme that catalyzes the production of alpha-amidated peptides from their glycine-extended precursors, a posttranslational modification often required for full biological activity. PAM activity in crude homogenates of bovine neurointermediate pituitary has an acidic pH optimum for the peptide substrate alpha-N-Ac-Tyr-Val-Gly. During purification, the pH optimum shifts, so that purified bovine (b)PAM exhibits an alkaline pH optimum for this substrate with virtually no activity below pH 6.5. A factor that restores the ability of purified bPAM to produce alpha-amidated products at pH 6 was identified. In rat anterior pituitary this factor (denoted SPAM for stimulator of PAM activity) was a soluble protein with a mol wt of 44 K by gel filtration; its stimulatory activity could be reduced or eliminated by trypsin digestion or boiling. SPAM stimulated PAM activity at acidic pH by increasing the apparent Vmax and decreasing the apparent Michaelis-Menten constant (Km) for the peptide substrate. Like PAM, SPAM activity is localized to the secretory granule. Levels of SPAM activity in various rat tissues correlated closely with levels of PAM activity, with the greatest amount of SPAM activity in atrium, anterior pituitary, and neurointermediate pituitary. The distribution of PAM and SPAM between soluble and membrane fractions also correlated closely. In AtT-20 cell lines transfected with a complementary DNA (cDNA) encoding the full-length bPAM precursor, both SPAM and PAM activities were increased compared to wild type cells; both activities were decreased in a cell line expressing an antisense rat (r)PAM mRNA. In marked contrast, an AtT-20 cell line transfected with a cDNA encoding a truncated, soluble form of bPAM had elevated levels of PAM activity, but levels of SPAM activity were not increased compared to wild-type cells. These results suggest that SPAM activity is closely linked to the expression of full-length PAM. The interaction of PAM and SPAM may represent a site for regulation of the synthesis of bioactive peptides, particularly at low intragranular pH.
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PMID:pH-dependent stimulation of peptidylglycine alpha-amidating monooxygenase activity by a granule-associated factor. 224 28