Biomaterial Database

Effect of heme oxygenase inhibitors on soluble guanylyl cyclase activity. 1998

L Serfass, and J N Burstyn

Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin, 53706, USA.

NO is the physiological activator of soluble guanylyl cyclase (sGC) thereby acting as a signaling molecule in the nervous and cardiovascular systems. Despite its poor sGC-activating ability, CO, produced by the enzyme heme oxygenase (HO), has also been implicated as a physiological stimulator of sGC in neurotransmission and vasorelaxation. Zinc protoporphyrin IX (ZnPPIX) and tin protoporphyrin IX (SnPPIX) are competitive HO inhibitors and have been used in studies implicating a messenger role for CO in the brain and periphery; however, little is known about the specificity of these metalloporphyrins. In the present study, the effects of ZnPPIX and SnPPIX on sGC activity have been investigated in vitro. Interestingly, purified sGC is markedly activated by SnPPIX (20- to 30-fold) but has a very low affinity for this metalloporphyrin (Ka = 4.9 microM); high concentrations of SnPPIX (25 microM) still activated the enzyme. On the other hand, sGC has a high affinity for ZnPPIX (Ka = 16.1 nM). ZnPPIX activates heme-containing sGC weakly at low (nM) concentrations (3- to 4-fold) but at higher concentrations, ZnPPIX is a potent inhibitor; at 2.5 microM, it inhibits the basal activity of sGC by about 80%. These results imply that HO inhibitors may affect cGMP levels independently of HO activity.

UI	MeSH Term	Description	Entries
D008665	Metalloporphyrins	Porphyrins which are combined with a metal ion. The metal is bound equally to all four nitrogen atoms of the pyrrole rings. They possess characteristic absorption spectra which can be utilized for identification or quantitative estimation of porphyrins and porphyrin-bound compounds.	Metalloporphyrin
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011524	Protoporphyrins	Porphyrins with four methyl, two vinyl, and two propionic acid side chains attached to the pyrrole rings. Protoporphyrin IX occurs in hemoglobin, myoglobin, and most of the cytochromes.
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006160	Guanosine Triphosphate	Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.	GTP,Triphosphate, Guanosine
D006162	Guanylate Cyclase	An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.	Guanyl Cyclase,Deoxyguanylate Cyclase,Guanylyl Cyclase,Inosinate Cyclase,Cyclase, Deoxyguanylate,Cyclase, Guanyl,Cyclase, Guanylate,Cyclase, Guanylyl,Cyclase, Inosinate
D006418	Heme	The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.	Ferroprotoporphyrin,Protoheme,Haem,Heme b,Protoheme IX
D006419	Heme Oxygenase (Decyclizing)	A mixed function oxidase enzyme which during hemoglobin catabolism catalyzes the degradation of heme to ferrous iron, carbon monoxide and biliverdin in the presence of molecular oxygen and reduced NADPH. The enzyme is induced by metals, particularly cobalt.	Haem Oxygenase,Heme Oxygenase,Oxygenase, Haem,Oxygenase, Heme