Heme b inhibits class III adenylyl cyclases.

Acidic lipid extracts from mouse liver, kidney, heart, brain, and lung inhibited human pseudoheterodimeric adenylyl cyclases (hACs) expressed in HEK293 cells. Using an acidic lipid extract from bovine lung, a combined MS- and bioassay-guided fractionation identified heme b as inhibitor of membrane-bound ACs. IC50 concentrations were 8-12 μM for the hAC isoforms. Hemopexin and bacterial hemophore attenuated heme b inhibition of hAC5. Structurally related compounds, such as hematin, protoporphyrin IX, and biliverdin, were significantly less effective. Monomeric bacterial class III ACs (mycobacterial ACs Rv1625c; Rv3645; Rv1264; cyanobacterial AC CyaG) were inhibited by heme b with similar efficiency. Surprisingly, structurally related chlorophyll a similarly inhibited hAC5. Heme b inhibited isoproterenol-stimulated cAMP accumulation in HEK293 cells. Using cortical membranes from mouse brain hemin efficiently and reversibly inhibited basal and Gsα-stimulated AC activity. The physiological relevance of heme b inhibition of the cAMP generating system in certain pathologies is discussed. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Sherif Elsabbagh, Marius Landau, Harald Gross, Anita Schultz, Joachim E Schultz. Heme b inhibits class III adenylyl cyclases. Cellular signalling. 2023 Mar;103:110568

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PMID: 36565898

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