Disease relevance of Pam

• This work is significant because PAM and the UBLs co-localize to the hypothalamus and the adrenal medulla and are both over-expressed in glioblastomas [1].
• Suppression of substance P biosynthesis in sensory neurons of dorsal root ganglion by prodrug esters of potent peptidylglycine alpha-amidating monooxygenase inhibitors [2].
• Taken together, these data suggest that hypothyroidism induces PAM mRNA levels by increasing its stability in the cytoplasm [3].
• Recently, we have shown that cholestyramine treatment prevents gut-derived endotoxemia in bile duct-ligated (BDL) rats (Houdijk APJ, Boermeester MA, Wesdorp RIC, Hack CE, van Leeuwen PAM: Tumor necrosis factor unresponsiveness following surgery in bile duct-ligated rats [4].
• Although endocrine cells typically package "foreign" secretory products together with endogenous products, pro-opiomelanocortin- and PAM-derived products encoded by adenovirus in large part were excluded from the LDCVs of SCG neurons [5].

Psychiatry related information on Pam

• In general, levels of NPY, PAM and kalirin mRNA showed similar transient increases after acute and repeated electroconvulsive shock [6].

High impact information on Pam

• Genes coding for the neuropeptide hormone pituitary adenylate cyclase activating polypeptide (PACAP) and the enzyme that processes PACAP's precursor to the mature form, peptidylglycine alpha-amidating monooxygenase, were upregulated by inositol depletion [7].
• Chronic treatment of ovariectomized rats with 17beta-estradiol decreased PAM mRNA levels to values comparable with those found in intact rats at proestrus [8].
• In the present study, high levels of peptidylglycine alpha-amidating monooxygenase (PAM), which catalyzes the two-step formation of bioactive alpha-amidated peptides from their glycine-extended precursors, have been found in the uterus [8].
• The levels of PAM transcripts changed markedly during the estrous cycle, reaching the highest levels at metestrus [8].
• These results demonstrate the presence of high levels of PAM in the uterus and indicate that estrogens are involved in regulating the expression of the enzyme in this tissue [8].

Chemical compound and disease context of Pam

• Primary rat pituitary cells cultures from hypo- and euthyroid rats in the presence of actinomycin D showed that hypothyroidism increased the half-life of PAM mRNA from 9-10 h to 15-17 h [3].

Biological context of Pam

• In this study, we demonstrate that PAM co-localizes in atrial secretory granules with the storage form of atrial natriuretic peptide (pro-ANP, amino acids 1-126), a hormone involved in the maintenance of blood pressure and fluid homeostasis [9].
• Comparison of the nucleotide sequences of rat, frog, and bovine PAM cDNAs reveals an extremely well conserved segment in the 3' untranslated region [10].
• The high degree of conservation in amino acid sequence throughout the catalytic, intragranular, and cytoplasmic domains of rat atrium, bovine pituitary, and frog skin PAM suggests that both the catalytic and noncatalytic domains of the protein subserve important functions [10].
• These three forms of PAM mRNA can be generated by alternative splicing [11].
• In the pituitary and submaxillary glands, PAM mRNAs lacking optimal Exon A were prevalent, as were PAM mRNAs lacking all or part of optional Exon B [12].

Anatomical context of Pam

• We demonstrate here by subcellular fractionation and biochemical analyses that PAM co-localizes with pro-ANP in secretory granules, where together they constitute the two most abundant membrane-associated proteins, accounting for approximately 95% of the total granular membrane protein [9].
• Additionally, we demonstrate that while pro-ANP is readily found in the soluble contents of the granule lumen, significant amounts remain tightly associated with the membranes even after vigorous washing and estimate the molar ratio of pro-ANP to PAM to be approximately 30:1 in the membrane fraction [9].
• We have isolated and sequenced cDNAs representing the two major classes of PAM mRNA in the adult rat heart atrium [10].
• In the heart and central nervous system, PAM mRNAs both containing and lacking optional Exon A were prevalent and almost all of the PAM mRNAs detected contained optional Exon B [12].
• Biotinylation studies established that the appearance of integral membrane PAM at the plasma membrane was stimulated along with hormone secretion [13].

Associations of Pam with chemical compounds

• ANP is not amidated by PAM, but rather is processed to its active form (amino acids 99-126) by the proteolytic cleavage of pro-ANP [9].
• Peptidyl-glycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the conversion of a variety of glycine-extended peptides into biologically active alpha-amidated product peptides in a reaction dependent on copper, ascorbate, and molecular oxygen [10].
• We examined the turnover of peptidylglycine alpha-amidating monooxygenase (PAM), a membrane enzyme involved in the final maturation of many peptides, and VAMP2, a vesicle soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) [13].
• We report here that thiorphan and tiopronin are substrates for PAM, exhibiting relatively low K(M,app) and V(MAX,app) values [14].
• Progesterone was without effect on PAM mRNA levels, indicating that the effect was specific for estradiol [8].

Other interactions of Pam

• Treatment with disulfiram, an inhibitor of the peptidylglycine alpha-amidating monooxygenase (PAM), reduced levels of TRH in the PP by 20% [15].
• Expression of catecholamine-synthesizing enzymes, peptidylglycine alpha-amidating monooxygenase, and neuropeptide Y mRNA in the rat adrenal medulla after acute systemic nicotine [16].
• Peptidylglycine alpha-amidating monooxygenase activity and TRH and CRF biosynthesis. Role of copper [17].
• Compared with Cu-adequate rats, Cu-deficient rats had lower activities of the cuproenzymes peptidylglycine alpha-amidating monooxygenase (PAM), cytochrome c oxydase (CCO), and Cu,Zn-superoxide dismutase (SOD) in all six brain regions studied [18].
• Kalirin is a brain-specific protein, first identified through its interaction with peptidylglycine-alpha-amidating monooxygenase [19].

Analytical, diagnostic and therapeutic context of Pam

• Respectively, light and electron microscopic immunohistochemistry show intense staining for PAM in atrial cardiomyocyctes and subcellular localization of PAM to secretory granules [9].
• Utilizing the polymerase chain reaction, two major patterns of distribution of forms of PAM mRNA were found [12].
• In situ hybridization studies were conducted to determine the tissue disposition and cell types expressing PAM [8].
• Northern blot analysis using cDNA probes encoding bovine pituitary PAM demonstrated higher levels of PAM mRNA in heart atrium than in anterior pituitary [20].
• Western blots of atrial and ventricular membranes revealed the existence of a developmental stage-specific distribution of PAM protein among forms ranging in mass from 125 to 94 kDa [21].

References