Cyclase

About: Cyclase is a research topic. Over the lifetime, 10162 publications have been published within this topic receiving 388566 citations.

Selective stimulation of adenyl cyclase of rat pineal gland by pharmacologically active catecholamines

Abstract: Adenyl cyclase activity of rat pineal gland homogenates was assayed in vitro by measuring the rate of formation of radioactive cyclic 39, 59-adenosine monophosphate (cyclic 39, 59-AMP) from its C 14 -labeled precursor, adenosine triphosphate. Enzyme activity was increased up to 3-fold by the addition of l -norepinephrine. Cyclic 39, 59-AMP formation was also enhanced by l -epinephrine and l -isoproterenol, but not by d -norepinephrine, dl -dihydroxymandelic acid, dl -normetanephrine, dopamine, tyramine, d -amphetamine or l -phenylephrine. Serotonin and histamine, which are present in the pineal gland and have been shown to increase cyclic 39, 59-AMP formation in other tissues, did not stimulate pineal adenyl cyclase. Similarly, the polypeptides, glucagon, adrenocorticotropic hormone and luteinizing hormone, which enhance the accumulation of the cyclic nucleotide in liver, adrenal cortex and corpus luteum, respectively, failed to stimulate adenyl cyclase of the pineal. Drugs such as guanethidine, cocaine and desmethylimipramine, which alter sympathetic responses by an action at adrenergic nerve endings, also failed to influence pineal adenyl cyclase activity. On the other hand, the beta adrenergic blocking agents, propranolol and dichloroisoproterenol, which affect beta adrenergic receptors, antagonized the norepinephrine-induced stimulation of enzyme activity. The alpha blockers, phenoxybenzamine and phentolamine, were considerably less effective in this regard. Thus, the results of these studies indicate that adenyl cyclase of rat pineal responds to specific adrenergic and adrenolytic drugs in a manner similar to that of a postjunctional beta adrenergic receptor.

The fumagillin biosynthetic gene cluster in Aspergillus fumigatus encodes a cryptic terpene cyclase involved in the formation of β-trans-bergamotene.

Abstract: Fumagillin 1 is a meroterpenoid from Aspergillus fumigatus that is known for its anti-angiogenic activity by binding to human methionine aminopeptidase 2 The genetic and molecular basis for biosynthesis of 1 had been an enigma despite the availability of the A fumigatus genome sequence Here, we report the identification and verification of the fma gene cluster, followed by characterization of the polyketide synthase and acyltransferase involved in biosynthesis of the dioic acid portion of 1 More significantly, we uncovered the elusive β-trans-bergamotene synthase in A fumigatus as a membrane-bound terpene cyclase

Isolation of an avian erythrocyte protein possessing ADP-ribosyltransferase activity and capable of activating adenylate cyclase

Abstract: An ADP-ribosyltransferase was purified ∼500-fold from the supernatant fraction of turkey erythrocytes. The enzyme hydrolyzed [carbonyl-14C]NAD to ADP-ribose and [carbonyl-14C]nicotinamide at a low rate. Nicotinamide formation from NAD was enhanced by arginine methyl ester > D-arginine ∼ L-arginine > guanidine; lysine, histidine, and citrulline were ineffective. Incubation of [adenine-U-14C]NAD and arginine methyl ester or arginine with the purified enzyme resulted in the formation of new compounds that contained 14C, reacted with ninhydrin, and quenched background fluorescence of thin-layer plates viewed in ultraviolet light. Their mobilities on thin-layer chromatograms were indistinguishable from those of ADP-ribosylarginine methyl ester and ADP-ribosylarginine formed during incubation of choleragen with NAD and arginine methyl ester or arginine, respectively [Moss, J. & Vaughan, M. (1977) J. Biol. Chem. 252, 2455-2457]. The purified transferase also catalyzed the incorporation of label from [adenine-14C]-NAD into lysozyme, histones and polyarginine. When the 14C-labeled lysozyme was incubated with snake venom phosphodiesterase, the radioactivity was released and, on thin-layer chromatograms, exhibited a mobility indistinguishable from that of 5′-AMP, as would be expected of an ADP-ribosylated protein, but not of a poly(ADP-ribosylated) product. The purified transferase activated rat brain adenylate cyclase and, as is the case with choleragen, activation was absolutely dependent on NAD. The presence in the avian erythrocyte of a protein that, like choleragen and Escherichia coli heat-labile enterotoxin, apparently activates adenylate cyclase and possesses ADP-ribosyl transferase activity is consistent with the view that the mechanisms through which the bacterial toxins produce pathology are not entirely foreign to vertebrate cells, at least some of which may possess and employ an analogous mechanism for activation of adenylate cyclase.

Effects of calcium on ACTH stimulation of the adrenal: separation of hormone binding from adenyl cyclase activation.

Abstract: CALCIUM is thought to be required for the binding of adrenal corticotrophic hormone (ACTH) to its cellular receptor1–5: in its absence, ACTH fails to stimulate steroidogenesis in the adrenal or lipolysis in adipose tissue1,2,6,7. The actions of other lipolytic hormones such as adrenaline and glucagon do not require calcium1–3. On the other hand, high calcium concentrations (>1 mM) inhibit the activation of adenyl cyclase by ACTH in subcellular particles from adipose and adrenal tissue8,9. The sites of these effects of calcium have not been unequivocally located.