guanylatecyklázok

Guanylatecyclases (GCs) are enzymes that catalyze the formation of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). cGMP is a crucial second messenger in various cellular signaling pathways, influencing a wide range of physiological processes including smooth muscle relaxation, neurotransmission, platelet aggregation, and photoreception. There are two main types of guanylate cyclases: membrane-bound guanylate cyclases (mGCs) and soluble guanylate cyclases (sGCs).

Membrane-bound guanylate cyclases are typically transmembrane proteins that possess an extracellular ligand-binding domain and an intracellular catalytic domain. They are activated by peptide hormones such as natriuretic peptides (atrial natriuretic peptide, brain natriuretic peptide, C-type natriuretic peptide). Upon binding of these peptides, the enzyme undergoes a conformational change, leading to the production of cGMP within the cell.

Soluble guanylate cyclases are heme-containing enzymes found in the cytoplasm. They are primarily activated by nitric oxide (NO). NO, upon its production by nitric oxide synthases, diffuses into cells and binds to the heme prosthetic group of sGC, relieving an inhibitory effect and activating the enzyme. This activation leads to a significant increase in intracellular cGMP levels. Additionally, sGC can also be activated by other stimuli, including carbon monoxide and oxidative stress.

The cGMP produced by guanylate cyclases acts on various downstream targets, most notably protein kinase G (PKG). PKG then phosphorylates a multitude of cellular proteins, leading to the diverse cellular responses mediated by cGMP. Dysfunction of guanylate cyclases or the downstream signaling pathway is implicated in various diseases, making them targets for therapeutic intervention.