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At least 1,225 records · Page 68Linked to original sources
PubMed1986

K-Nutrition, Growth Bud Formation, and Amine and Hydroxycinnamic Acid Amide Contents in Leaf Explants of Nicotiana tabacum Variety Xanthi n.c. Cultivated in Vitro.

The effects of K-nutrition on growth (increase of fresh weight), bud formation (time of emergence, number of buds), and amine and hydroxycinnamic acid amide contents in foliar explants of Nicotiana tabacum cv Xanthi n.c. cultivated in vitro were examined. In K-deficient medium and in high K medium growth and bud formation were markedly inhibited. Marked changes of amine content (a diamine, putrescine; a phenolic amine, phenethylamine) were observed after a few days of culture. No apparent relationship was found between these amines and growth or bud differentiation. In contrast, changes in hydroxycinnamic acid levels were shown to correlate well with growth and bud formation. The greatest stimulation of budding and growth was correlated with the greatest accumulation of these amides. The highest contents of hydroxycinnamic acid amides were found during the first 15 days in culture when intensive cell division took place. Then they declined sharply after 26 days in culture as the rate of cell division decreased and differentiation occurred.

Journal Article↗
PubMed2005

Mapping protein energy landscapes with amide hydrogen exchange and mass spectrometry: I. A generalized model for a two-state protein and comparison with experiment.

Protein amide hydrogen exchange (HDX) is a convoluted process, whose kinetics is determined by both dynamics of the protein and the intrinsic exchange rate of labile hydrogen atoms fully exposed to solvent. Both processes are influenced by a variety of intrinsic and extrinsic factors. A mathematical formalism initially developed to rationalize exchange kinetics of individual amide hydrogen atoms is now often used to interpret global exchange kinetics (e.g., as measured in HDX MS experiments). One particularly important advantage of HDX MS is direct visualization of various protein states by observing distinct protein ion populations with different levels of isotope labeling under conditions favoring correlated exchange (the so-called EX1 exchange mechanism). However, mildly denaturing conditions often lead to a situation where the overall HDX kinetics cannot be clearly classified as either EX1 or EX2. The goal of this work is to develop a framework for a generalized exchange model that takes into account multiple processes leading to amide hydrogen exchange, and does not require that the exchange proceed strictly via EX1 or EX2 kinetics. To achieve this goal, we use a probabilistic approach that assigns a transition probability and a residual protection to each equilibrium state of the protein. When applied to a small protein chymotrypsin inhibitor 2, the algorithm allows complex HDX patterns observed experimentally to be modeled with remarkably good fidelity. On the basis of the model we are now in a position to begin to extract quantitative dynamic information from convoluted exchange kinetics.

Algorithms↗
PubMed1975

Polymorphic acetylation of procaine amide in healthy subjects.

The acetylation of procaine amide has been studied by means of gas liquid chromatography in 33 healthy human volunteers. The acetylator phenotype was determined by measuring unchanged and acetylated sulphapyridine in urine. Slow acetylators of sulphapyridine excreted significantly less procaine amide in acetylated from in the urine than rapid acetylators (9 plus or minus 1% against 19 plus or minus 4%). Hence, it is suggested that the acetylation of procaine amide is subject to the same genetic polymorphism as that of isoniazid and some sulfonamides.

Acetylation↗
PubMed1984

Potential uses of human pancreatic growth hormone-releasing factor 1-44 amide.

A family of growth hormone releasing peptides have been isolated and characterized from human pancreatic islet cell tumours. We have compared the growth hormone release in normal volunteers and patients with various hypothalamo-pituitary disorders, following direct stimulation of the pituitary using 50 micrograms of the most potent homologue, hp GRF 1-44 amide i.v. with that following indirect stimulation using oral clonidine 0.15 mg/m2, which depends on intact hypothalamic mechanisms. These tests both produced a wide variation in GH response in normal volunteers, considerable GH release following hp GRF 1-44 amide but little after clonidine in idiopathic GH deficiency, and indistinguishable, negligible responses in patients with craniopharyngiomas and pituitary tumours associated with GH deficiency. Two untreated acromegalics showed GH increments in the normal range despite elevated basal levels. It is concluded that hp GRF 1-44 amide is of limited diagnostic value by itself, but may be of considerable therapeutic use in patients with idiopathic GH deficiency.

Acromegaly↗
PubMed1990

Characterization of an alpha-amidating activity in a human pancreatic tumour secreting vasoactive intestinal peptide (VIP).

A case of watery diarrhoea hypokalaemia achlorhydria (WDHA) syndrome due to a pancreatic tumour and identified by VIP plasma level, VIP immunocytochemistry, and ultrastructural analysis of tumour sections, is reported. Since VIP is the mediator of the syndrome and is biologically active under its amidated form, the enzymatic alpha-amidating activity was investigated and characterized in tumour extract; using the synthetic substrate D-Tyr-Val-Gly, the enzyme displayed an optimal activity at pH 7.0, under aerobic conditions and with 35 microM CuSO4 and 3 mM ascorbate as co-factors. The Kmax and Vmax values of the enzymatic activity were 133.7 microM and 26.9 pmol/h/micrograms protein respectively. Its molecular weight, determined by molecular sieving, was close to 36 kDa. Other tumours of the human endocrine pancreas were also investigated for the enzymatic activity. The clinical interest of studying the regulation of the alpha-amidating activity in such tumours is discussed.

Female↗
PubMed1985

Synthesis and biological activity of linear and cyclic enkephalins modified at the Gly3-Phe4 amide bond.

As part of our continuing effort to define structure-activity relationships for enkephalin and design enzymatically resistant analogs, we report the synthesis and biological activities of linear and cyclic enkephalin analogs modified at the Gly3-Phe4 amide bond. The partial retro-inverso enkephalin analog Tyr-D-Ala-gGly-(R,S)-mPhe-Leu-NH2 and its cyclic counterpart, Tyr-cyclo[D-A2 bu-gGly-(R,S)-mPhe-Leu-], were synthesized as diastereomeric mixtures using solution methodology. The racemic benzylmalonate allowed the linear analog to be synthesized by fragment coupling at the reversed bond. Cyclization of the second analog was carried out at high concentration, eliminating formation of polymer by the use of an insoluble base. All gem-diaminoalkyl residues were prepared by conversion of peptidyl amides with benzene iodonium bis(trifluoroacetate). Diastereomers of both compounds were separable by reverse phase HPLC but those of the linear compound racemized rapidly under conditions of testing and were therefore tested together. All analogs tested had activities ranging from 6 to 14% of the activity of Leu enkephalin, indicating that the Gly3-Phe4 amide bond is important, though not crucial, for receptor binding.

Animals↗
PubMed1990

Peptide substrate specificity of the alpha-amidating enzyme isolated from rat medullary thyroid CA-77 cells.

The kinetic parameters were obtained for enzymatic alpha-amidation of peptides of the form N-dansyl-(Gly)4-X-Gly-OH, in which the amino acid at position X was substituted with each of the 20 natural amino acids. The enzyme used in these studies was a highly enriched preparation of alpha-amidating enzyme secreted by a clonal (CA-77) cell line which actively expresses mature alpha-amidated peptides. A 130-fold and 11-fold variation respectively in apparent Km and Vmax values was observed. The effect of the amino acid side chain at position X in stabilization of the enzyme-substrate complex decreased through the series X = planar aromatic or sulfur containing greater than neutral aliphatic greater than polar and basic greater than cyclic aliphatic or acidic.

Animals↗
PubMed1993

Identification and characterization of an amidating enzyme in ovine heart.

1. Levels of peptidylglycine alpha-amidating mono-oxygenase (PAM) activity were examined in sheep and rat heart. This enzyme is responsible for alpha-amidation of a large number of peptide hormones, a modification essential for the bioactivity of these peptides. 2. PAM activity was measured in membrane and soluble fractions of atrial and ventricular homogenates by monitoring the amidation of iodinated synthetic substrate ([125I]-Ac-Tyr-Val-Gly). 3. PAM activity in both species resided almost exclusively in the atria rather than the ventricles, and similar levels of activity were found in left and right atria. Membrane-associated activity was 50-to 100-fold greater than soluble activity in the sheep, yet was only five- to 10-fold greater in the rat, indicating a larger proportion of soluble enzyme in the rat atrium. 4. Similar apparent Km values were found for atrial membrane-associated activity in both species (15.6 and 17.4 mumol/L for rat right and left atria, 16.7 and 15.6 mumol/L for sheep right and left atria); however, the maximum velocity (Vmax) levels were higher in the rat (40.5 and 43.9 pmol/micrograms per h vs 12.8 and 15.1 pmol/micrograms per h). 5. Because expression of many peptides and processing enzymes can be regulated by steroid hormones, the possible effects of chronic glucocorticoid administration (1 mg dexamethasone i.m. twice daily for 10 days) on PAM levels were tested in four sheep, with four sheep receiving saline only as controls. There was no discernible effect of dexamethasone on either the distribution or the kinetics of PAM activity in the sheep heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Neurosecretory vesicles contain soluble and membrane-associated monofunctional and bifunctional peptidylglycine alpha-amidating monooxygenase proteins.

Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the COOH-terminal amidation of neuropeptides in a reaction requiring the sequential action of two enzymes contained within this bifunctional protein. The CNS contains primarily transcripts encoding rPAM-1 and rPAM-2, integral membrane proteins differing by the presence or absence of a noncatalytic domain separating the two enzymes. Subcellular fractionation of adult rat hypothalamus and hippocampus demonstrated the localization of both enzymatic activities to fractions enriched in neurosecretory vesicles. Upon separation of the soluble contents from the membranes of neurosecretory vesicles, 30-40% of both enzymatic activities was recovered in the soluble fraction. Over 40% of both enzymatic activities remained membrane-associated following removal of peripheral membrane proteins. Antisera specific to different regions of PAM were used to identify intact rPAM-1 and rPAM-2, a monofunctional integral membrane peptidyl-alpha-hydroxy-glycine alpha-amidating lyase protein generated from rPAM-1, and a noncatalytic COOH-terminal fragment as the major PAM proteins in carbonate-washed membranes. Endoproteolytic processing generated large amounts of soluble, monofunctional forms of both enzymes from rPAM-1 and smaller amounts of a soluble, bifunctional PAM protein from rPAM-2. A significant amount of both monofunctional enzymes lacking the transmembrane domain was tightly associated with membranes. Whereas soluble mono- and bifunctional enzymes may be released upon exocytosis of neurosecretory vesicles, membrane-associated PAM proteins may remain on the cell surface or be internalized.

Amidine-Lyases↗
PubMed2006

Siro(haem)amide in Allochromatium vinosum and relevance of DsrL and DsrN, a homolog of cobyrinic acid a,c-diamide synthase, for sulphur oxidation.

In the purple sulphur bacterium Allochromatium vinosum, the prosthetic group of dissimilatory sulphite reductase (DsrAB) was identified as siroamide, an amidated form of the classical sirohaem. The genes dsrAB are the first two of a large cluster of genes necessary for the oxidation of sulphur globules stored intracellularly during growth on sulphide and thiosulphate. DsrN is homologous to cobyrinic acid a,c diamide synthase and may therefore catalyze glutamine-dependent amidation of sirohaem. Indeed, an A. vinosumDeltadsrN in frame deletion mutant showed a significantly reduced sulphur oxidation rate that was fully restored upon complementation with dsrN in trans. Sulphite reductase was still present in the DeltadsrN mutant. DsrL is a homolog of the small subunits of bacterial glutamate synthases and was proposed to deliver glutamine for sirohaem amidation. However, recombinant DsrL does not exhibit glutamate synthase activity nor does the gene complement a glutamate synthase-deficient Escherichia coli strain. Deletion of dsrL showed that the encoded protein is absolutely essential for sulphur oxidation in A. vinosum.

Bacterial Proteins↗
PubMed1995

The NO synthase inhibitor L-NNA depresses neurohypophysial vasopressin but not its precursor amidating enzymes in salt-loaded rats.

The arginine vasopressin (AVP) producing hypothalamo-neurohypophysial system also has high activities of NO-synthase. Vasopressin production and secretion is drastically upregulated during salt intake and the NO-producing enzyme may be involved. We have studied the influence of the NO-synthase inhibitor NG-nitro-L-arginine (L-NNA) on neurohypophysial and hypothalamic AVP and its amidating enzymes in salt-loaded and control rats as well as on stimulated AVP release in vitro in such rats. Rats were given 2% NaCl solution as the only fluid for 4 days and then returned to tap water. The specific amount of AVP (microgram (mg protein)-1) and the activities of peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), components of its amidating processing enzyme in the supraoptic (SON) and paraventricular nuclear (PVN) regions, did not change during the salt-loading or the following recovery period. In contrast, the AVP and PHM and PAL in the neurohypophysis fell drastically during the salt loading. After that, PHM and PAL increased even more rapidly than AVP, the latter reaching control levels in about 10 days. Salt loading did not change the protein content of the neurohypophysis. When salt loading was performed after administration of L-NNA, the neurohypophysial AVP at the end of the salt loading and 3 days later was lower than in rats not receiving L-NNA, whereas PHM and PAL were not affected. Fractional AVP release from isolated neurohypophyses of salt loaded rats treated with L-NNA and stimulated with K+ was similar to that found in non-treated rats. It is suggested that L-NNA may affect translation or precursor processing of AVP.

Amidine-Lyases↗
PubMed1996

The failure of substrate pKa to influence the microsomal formation of amides from N-benzylamines: the microsomal metabolism of N-benzyl pyrrolidine, N-benzyl carbazole and N-acetyl-N-benzyl-4-methylaniline.

The in-vitro hepatic microsomal metabolism of N-benzylpyrrolidine (NBP), N-benzylcarbazole (NBC) and N-acetyl-N-benzyl-4-methylaniline (NANBMA) has been studied, using hamster microsomal preparations, to establish whether the corresponding amide is formed. Amide formation was not observed with any of the substrates utilized, although several metabolic products were detected by HPLC with UV detection. These included the oxidative debenzylation products (for all substrates), ring hydroxylated products (for NBC) and a lactam metabolite (for NBP). The results support the concept that the metabolic conversion of benzylic amines to the corresponding amide involves an N-oxidative step.

Aniline Compounds↗
PubMed1997

Amidation of bioactive peptides: the structure of peptidylglycine alpha-hydroxylating monooxygenase.

Many neuropeptides and peptide hormones require amidation at the carboxyl terminus for activity. Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the amidation of these diverse physiological regulators. The amino-terminal domain of the bifunctional PAM protein is a peptidylglycine alpha-hydroxylating monooxygenase (PHM) with two coppers that cycle through cupric and cuprous oxidation states. The anomalous signal of the endogenous coppers was used to determine the structure of the catalytic core of oxidized rat PHM with and without bound peptide substrate. These structures strongly suggest that the PHM reaction proceeds via activation of substrate by a copper-bound oxygen species. The mechanistic and structural insight gained from the PHM structures can be directly extended to dopamine beta-monooxygenase.

Animals↗
PubMed2006

Engineered biosynthesis of a novel amidated polyketide, using the malonamyl-specific initiation module from the oxytetracycline polyketide synthase.

Tetracyclines are aromatic polyketides biosynthesized by bacterial type II polyketide synthases (PKSs). Understanding the biochemistry of tetracycline PKSs is an important step toward the rational and combinatorial manipulation of tetracycline biosynthesis. To this end, we have sequenced the gene cluster of oxytetracycline (oxy and otc genes) PKS genes from Streptomyces rimosus. Sequence analysis revealed a total of 21 genes between the otrA and otrB resistance genes. We hypothesized that an amidotransferase, OxyD, synthesizes the malonamate starter unit that is a universal building block for tetracycline compounds. In vivo reconstitution using strain CH999 revealed that the minimal PKS and OxyD are necessary and sufficient for the biosynthesis of amidated polyketides. A novel alkaloid (WJ35, or compound 2) was synthesized as the major product when the oxy-encoded minimal PKS, the C-9 ketoreductase (OxyJ), and OxyD were coexpressed in CH999. WJ35 is an isoquinolone compound derived from an amidated decaketide backbone and cyclized with novel regioselectivity. The expression of OxyD with a heterologous minimal PKS did not afford similarly amidated polyketides, suggesting that the oxy-encoded minimal PKS possesses novel starter unit specificity.

Genetic Engineering↗
PubMed2005

Mammalian peptidylglycine alpha-amidating monooxygenase mRNA expression can be modulated by the La autoantigen.

Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the COOH-terminal alpha-amidation of peptidylglycine substrates, yielding amidated products. We have previously reported a putative regulatory RNA binding protein (PAM mRNA-BP) that binds specifically to the 3' untranslated region (UTR) of PAM-mRNA. Here, the PAM mRNA-BP was isolated and revealed to be La protein using affinity purification onto a 3' UTR PAM RNA, followed by tandem mass spectrometry identification. We determined that the core binding sequence is approximately 15-nucleotides (nt) long and is located 471 nt downstream of the stop codon. Moreover, we identified the La autoantigen as a protein that specifically binds the 3' UTR of PAM mRNA in vivo and in vitro. Furthermore, La protein overexpression caused a nuclear retention of PAM mRNAs and resulted in the down-regulation of endogenous PAM activity. Most interestingly, the nuclear retention of PAM mRNA is lost upon expressing the La proteins that lack a conserved nuclear retention element, suggesting a direct association between PAM mRNA and La protein in vivo. Reporter assays using a chimeric mRNA that combined luciferase and the 3' UTR of PAM mRNA demonstrated a decrease of the reporter activity due to an increase in the nuclear localization of reporter mRNAs, while the deletion of the 15-nt La binding site led to their clear-cut cytoplasmic relocalization. The results suggest an important role for the La protein in the modulation of PAM expression, possibly by mechanisms that involve a nuclear retention and perhaps a processing of pre-PAM mRNA molecules.

Amino Acid Sequence↗
PubMed1987

Growth hormone responses to hp GRF 1-44 amide, bromocriptine and stress in acromegaly are correlated.

The results of testing growth hormone (GH) reserve using human pancreatic growth hormone-releasing factor 1-44 amide (hp GRF 1-44 amide) have been compared with the GH responses in a variety of other dynamic tests in seven acromegalic patients. The GH release following hp GRF 1-44 amide correlated with the GH suppression following bromocriptine, but showed an inverse correlation with the GH release following stress tests (insulin-induced hypoglycaemia/glucagon). There was no correlation between the GH responses in these three tests and any of the other tests: TRH, GnRH and glucose. A hypothesis is proposed to explain these findings on the basis of varying degrees of GH secretion from adenomatous and normal pituitary somatotrophs in acromegaly.

Acromegaly↗
PubMed1975

Subcellular and functional effects of quinidine, procaine amide, and lidocaine on rat myocardium.

Different antiarrhythmic agents such as quinidine, procaine amide, and lodocaine at 1 mM concentrations were found to depress the ability of an isolated perfused rat heart to generate contractile force. Quinidine, but not procaine amide or lidocaine, decreased calcium uptake by both mitochondrial and microsomal fractions at different concentrations of calcium. The mitochondrial phosphorylation rate, respiratory control index, and state 3 oxygen consumption, but not ADP:O ratio and state 4 oxygen consumption, were depressed by only quinidine. None of these agents had any effect on myofibrillar Mg2+-ATPase or Ca2+-stimulated ATPase activities. On the other hand, sarcolemmal Mg2+-ATPase and Ca2+-ATPase activities, but not Na+-K+-ATPase activity, were increased by all these drugs. The sarcolemmal adenylate cyclase (EC 4.6.1.1) activity was decreased by quinidine only. These results suggest some similarities and differences in the sites of action of quinidine, procaine amide, and lidocaine within the myocardium.

Adenosine Triphosphatases↗
PubMed1996

Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats.

Glucagon-like peptide (GLP)-1-(7-36) amide and its pancreatic receptors are important for control of blood glucose levels. However, rat GLP-1 receptors are also localized in the brain, in hypothalamus, and in areas without a blood-brain barrier. When rats were kept on a food restriction schedule, intracerebroventricular injection of GLP-1 just before food was offered inhibited food intake. However, peripheral GLP-1 administration by intraperitoneal injection had little effect. GLP-1 effects on water intake and output were also investigated. Intracerebroventricular GLP-1 profoundly inhibited angiotensin II-induced drinking behavior in rats, and water intake was suppressed by exogenous GLP-1 in rats habituated to a water restriction schedule. These effects were reproduced by intraperitoneal administration of GLP-1. Furthermore, intracerebroventricular GLP-1 stimulated urinary excretion of water and sodium. The centrally elicited effects were blocked by the GLP-1 antagonist exendin-(9-39) amide, whereas the N-terminally extended and inactive GLP-1-(1-36) amide had no effect on feeding and drinking. GLP-1 had no effect in behavioral assays measuring exploratory locomotor activity and conditioned taste aversion. In conclusion, GLP-1 may play a physiological role in regulation of both ingestion and the water and salt homeostasis.

Animals↗