Guanylate cyclase GudangMovies21 Rebahinxxi LK21

      Guanylate cyclase (EC 4.6.1.2, also known as guanyl cyclase, guanylyl cyclase, or GC; systematic name GTP diphosphate-lyase (cyclizing; 3′,5′-cyclic-GMP-forming)) is a lyase enzyme that converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) and pyrophosphate:

      GTP = 3′,5′-cyclic GMP + diphosphate
      It is often part of the G protein signaling cascade that is activated by low intracellular calcium levels and inhibited by high intracellular calcium levels. In response to calcium levels, guanylate cyclase synthesizes cGMP from GTP. cGMP keeps cGMP-gated channels open, allowing for the entry of calcium into the cell.
      Like cAMP, cGMP is an important second messenger that internalizes the message carried by intercellular messengers such as peptide hormones and nitric oxide and can also function as an autocrine signal. Depending on cell type, it can drive adaptive/developmental changes requiring protein synthesis. In smooth muscle, cGMP is the signal for relaxation, and is coupled to many homeostatic mechanisms including regulation of vasodilation, vocal tone, insulin secretion, and peristalsis. Once formed, cGMP can be degraded by phosphodiesterases, which themselves are under different forms of regulation, depending on the tissue.


      Reaction


      Guanylate cyclase catalyzes the reaction of guanosine triphosphate (GTP) to 3',5'-cyclic guanosine monophosphate (cGMP) and pyrophosphate:











      Effects


      Guanylate cyclase is found in the retina (RETGC) and modulates visual phototransduction in rods and cones. It is part of the calcium negative feedback system that is activated in response to the hyperpolarization of the photoreceptors by light. This causes less intracellular calcium, which stimulates guanylate cyclase-activating proteins (GCAPs). Studies have shown that cGMP synthesis in cones is about 5-10 times higher than it is in rods, which may play an important role in modulating cone adaption to light. In addition, studies have shown that zebrafish express a higher number of GCAPs than mammals, and that zebrafish GCAPs can bind at least three calcium ions.
      Guanylate cyclase 2C (GC-C) is an enzyme expressed mainly in intestinal neurons. Activation of GC-C amplifies the excitatory cell response that is modulated by glutamate and acetylcholine receptors. GC-C, while known mainly for its secretory regulation in the intestinal epithelium, is also expressed in the brain. To be specific, it is found in the somata and dendrites of dopaminergic neurons in the ventral tegmental area (VTA) and the substantia nigra. Some studies implicate this pathway as having a role in attention deficiency and hyperactive behavior.
      Soluble guanylate cyclase contains a molecule of heme, and is activated primarily by the binding of nitric oxide (NO) to that heme. sGC is primary receptor for NO a gaseous, membrane-soluble neurotransmitter. sGC expression has been shown to be highest in the striatum compared to other brain regions and has been explored as a possible candidate for restoring striatal dysfunction in Parkinson's disease. sGC acts as an intracellular intermediary for regulating dopamine and glutamate. Upregulation, which creates neuronal sensitivity, of the cGMP in a dopamine-depleted striatum has been associated with the symptoms of Parkinson's. Increased intracellular cGMP has been shown to contribute to excessive neuron excitability and locomotor activity. Activation of this pathway can also stimulate presynaptic glutamate release and cause an upregulation of AMPA receptors postsynaptically.


      Types


      There are membrane-bound (type 1, guanylate cyclase-coupled receptor) and soluble (type 2, soluble guanylate cyclase) forms of guanylate cyclases.
      Membrane bound guanylate cyclases include an external ligand-binding domain (e.g., for peptide hormones such as BNP and ANP), a transmembrane domain, and an internal catalytic domain homologous to adenylyl cyclases. Recently, a directly light-gated guanylate cyclase has been discovered in an aquatic fungus.
      In the mammalian retina, two forms of guanylate cyclase have been identified, each encoded by separate genes; RETGC-1 and RETGC-2. RETGC-1 has been found to be expressed in higher levels in cones compared to rod cells. Studies have also shown that mutations in the RETGC-1 gene can lead to cone-rod dystrophy by disrupting the phototransduction processes.


      Mutations


      Cone dystrophy (COD) is a retinal degradation of photoreceptor function wherein cone function is lost at the onset of the dystrophy but rod function is preserved until almost the end. COD has been linked to several genetic mutations including mutations in the guanylate cyclase activator 1A (GUCA1A) and guanylate cyclase 2D (GUY2D) among other enzymes. To be specific, GUY2D codes for RETGC-1, which is involved in cone adaptation and photoreceptor sensitivity by synthesizing cGMP. Low concentrations of calcium cause the dimerization of RETGC-1 proteins through stimulation from guanylate cyclase-activating proteins (GCAP). This process happens at amino acids 817-857, and mutations in this region increase RETGC-1 affinity for GCAP. This works to alter the calcium sensitivity of the neuron by allowing mutant RETGC-1 to be activated by GCAP at higher calcium levels than the wild-type. Because RETGC-1 produces cGMP, which keeps cyclic nucleotide-gated channels open allowing the influx of calcium, this mutation causes extremely high intracellular calcium levels. Calcium, which plays many roles in the cell and is tightly regulated, disrupts the membrane when it appears in excess. Also, calcium is linked to apoptosis by causing the release of cytochrome c. Therefore, mutations in the RETGC-1 can cause COD by increasing intracellular calcium levels and stimulating cone photoreceptor death.


      See also


      Adenylyl cyclase
      Cyclic guanosine monophosphate
      Guanylyl cyclase activator (protein)


      References




      External links


      Guanylate+Cyclase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

    Kata Kunci Pencarian:

    guanylate cyclase enzymeguanylate cyclase stimulatorguanylate cyclase stimulatorsguanylate cyclase cgmpguanylate cyclaseguanylate cyclase c agonistsguanylate cyclase activatorsguanylate cyclase functionguanylate cyclase receptorguanylate cyclase inhibitor drugs
    Soluble Guanylate Cyclase

    Soluble Guanylate Cyclase

    Guanylate Cyclase - Others - BioCrick

    Guanylate Cyclase - Others - BioCrick

    Guanylate Cyclase | Semantic Scholar

    Guanylate Cyclase | Semantic Scholar

    Guanylate Cyclase | Semantic Scholar

    Guanylate Cyclase | Semantic Scholar

    APExBIO - Guanylate Cyclase - Others - Signaling Pathways

    APExBIO - Guanylate Cyclase - Others - Signaling Pathways

    Guanylate cyclase-IN-1 | Guanylate Cyclase Inhibitor | MedChemExpress

    Guanylate cyclase-IN-1 | Guanylate Cyclase Inhibitor | MedChemExpress

    Guanylate cyclase; Guanyl Cyclase

    Guanylate cyclase; Guanyl Cyclase

    Medicowesome: Soluble Guanylate Cyclase Stimulators notes and mnemonic

    Medicowesome: Soluble Guanylate Cyclase Stimulators notes and mnemonic

    Medicowesome: Soluble Guanylate Cyclase Stimulators notes and mnemonic

    Medicowesome: Soluble Guanylate Cyclase Stimulators notes and mnemonic

    Structure of soluble guanylate cyclase | Download Scientific Diagram

    Structure of soluble guanylate cyclase | Download Scientific Diagram

    Guanylate Cyclase and Cyclic GMP: Buy Guanylate Cyclase and Cyclic GMP ...

    Guanylate Cyclase and Cyclic GMP: Buy Guanylate Cyclase and Cyclic GMP ...

    Synthesis of guanylate cyclase activator 8 | Download Scientific Diagram

    Synthesis of guanylate cyclase activator 8 | Download Scientific Diagram

    Search Results

    guanylate cyclase

    Daftar Isi

    Guanylate cyclase - Wikipedia

    Guanylate cyclase (EC 4.6.1.2, also known as guanyl cyclase, guanylyl cyclase, or GC; systematic name GTP diphosphate-lyase (cyclizing; 3′,5′-cyclic-GMP-forming)) is a lyase enzyme that converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) and pyrophosphate: [1] GTP = 3′,5′-cyclic GMP + diphosphate

    Biochemistry, Guanylate Cyclase - StatPearls - NCBI Bookshelf

    Jul 30, 2023 · Guanylyl cyclase (also known as guanylate cyclase) is an enzyme that catalyzes the synthesis of cyclic guanosine 3′,5′-monophosphate (cGMP) from guanosine 5' triphosphate (GTP). Guanylyl cyclase exists in both a membrane-bound and soluble form in the cell.

    List of Guanylate cyclase-C agonists - Drugs.com

    Guanylate cyclase-C agonists are used to treat irritable bowel syndrome with constipation and chronic constipation of unknown cause (idiopathic constipation). They work by increasing intestinal fluid secretion, which can soften stools and stimulate bowel movements.

    Guanylate Cyclase - an overview | ScienceDirect Topics

    Guanylate cyclase-C (GC-C) is a transmembrane receptor activated by bacterial heat-stable enterotoxins and by the endogenous hormones guanylin and uroguanylin. GC-C plays key roles in the regulation of intestinal fluid and electrolyte homeostasis.

    Guanylyl cyclase structure, function and regulation - PMC

    Nitric oxide, bicarbonate, natriuretic peptides (ANP, BNP and CNP), guanylins, uroguanylins and guanylyl cyclase activating proteins (GCAPs) activate a family of enzymes variously called guanyl, guanylyl or guanylate cyclases that catalyze the ...

    Guanylate Cyclase C: A Current Hot Target, from Physiology to ... - PubMed

    Background: Guanylate cyclase C (GC-C) receptor is a transmembrane receptor, predominantly expressed in intestinal epithelial cells, which is considered to play a main role in homeostasis and function of the digestive tract. The endogenous ligands for this receptor are the paracrine hormones uroguanylin and guanylin.

    Guanylyl Cyclase - Basic Neurochemistry - NCBI Bookshelf

    Guanylyl cyclase, also termed guanylate cyclase, catalyzes the synthesis of cGMP from GTP in a reaction analogous to that shown in Figure 22-2 for adenylyl cyclase. Two major classes of guanylyl cyclase are known to exist, identified originally on the basis of their subcellular distribution: membrane-bound and soluble [24–27].

    Structural insights into the mechanism of human soluble guanylate cyclase

    Sep 12, 2019 · Soluble guanylate cyclase (sGC) is the primary sensor of nitric oxide. It has a central role in nitric oxide signalling and has been implicated in many essential physiological processes and ...

    Current Modulation of Guanylate Cyclase Pathway …

    In mammals, there are two key types of guanylate cyclases (GC), classified according to localization of enzymes in the cell. The first is called guanylate cyclase-coupled receptor or membrane-bound guanylate cyclase (mGC). The second is …

    Guanylate Cyclase - an overview | ScienceDirect Topics

    Soluble guanylate cyclase is a nitric-oxide (NO) regulated heme-based sensor involved in a variety of important biological processes, including smooth muscle relaxation, platelet aggregation, and neurotransmission. This heterodimeric protein contains a larger α-subunit and a smaller β-subunit.