Protoporphyrin IX activates the Mg dependent guanylate cyclase from rat liver plasma membranes.
In the presence of Mg-GTP, the rat liver guanylate cyclase, in either intact membranes or trypsin solubilized form, was stimulated by protoporphyrin IX 6 to 10-fold. However, when Mn-GTP was the substrate, protoporphyrin IX activated the membrane-bound guanylate cyclase only 50%, in contrast to the marked activation reported for the cytosolic enzyme. Meso- and deuteroporphyrin IX, hematoporphyrin and coproporphyrin III also activated membrane guanylate cyclase while uroporphyrin III, and hemin had no effect. Basal, Mg2+-dependent activity exhibited two classes of catalytic sites with apparent Km values of 2 mM and 0.12 mM. Activation by protoporphyrin resulted in the disappearance of the low affinity sites. The activated enzyme exhibited Michaelis-Menten kinetics and no alteration in its requirement for excess Mg2+. These data indicate that, in the presence of Mg2+, a heme-like structure can interact with the membrane-bound guanylate cyclase and regulate its activity.
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008274:Magnesium / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D012995:Solubility; D014357:Trypsin
D011166:Porphyrins; D011524:Protoporphyrins; D009569:Nitric Oxide; D014357:Trypsin; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D008274:Magnesium