Related Experiment Video

Updated: Aug 19, 2026

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
09:39

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications

Published on: January 27, 2014

Mechanism of molybdate activation of adenylate cyclase

J M Richards, N I Swislocki

    Biochimica Et Biophysica Acta
    |December 4, 1981
    PubMed

    Insights

    Molybdate and fluoride activate rat liver adenylate cyclase through a mechanism distinct from glucagon or guanyl nucleotides. Their stimulatory effects are additive and do not require guanyl nucleotide for activation.

    Area of Science:

    • Biochemistry
    • Enzymology
    • Molecular Pharmacology

    Background:

    • Adenylate cyclase is a key enzyme in cellular signal transduction.
    • Understanding its activation mechanisms is crucial for drug development.
    • Previous studies have identified various activators, including hormones and nucleotides.

    Purpose of the Study:

    • To investigate the activation mechanism of rat liver plasma membrane adenylate cyclase by molybdate.
    • To compare molybdate's effects with known activators like glucagon, Gpp(NH)p, and fluoride.
    • To elucidate the distinct pathways involved in adenylate cyclase activation.

    Main Methods:

    • Enzyme activity assays on rat liver plasma membranes.
    • Solubilization of adenylate cyclase using detergents.
    • Stimulation experiments using molybdate, fluoride, glucagon, Gpp(NH)p, and GTP.
    • Analysis of additive effects and requirement for guanyl nucleotides.
    • pH profile analysis and cholera toxin treatment.

    Main Results:

    • Molybdate and fluoride effectively stimulate detergent-solubilized adenylate cyclase, unlike glucagon.
    • The stimulatory effects of molybdate and fluoride are additive with GTP and do not require guanyl nucleotides.
    • Molybdate and fluoride activation mechanisms are distinct from glucagon and guanyl nucleotides.
    • pH profiles and cholera toxin sensitivity indicate similar activation mechanisms for molybdate and fluoride.

    Conclusions:

    • Molybdate and fluoride activate adenylate cyclase via a mechanism independent of guanyl nucleotides and distinct from hormonal activation.
    • Fluoride and molybdate likely share a similar activation pathway.
    • These findings provide insights into the complex regulation of adenylate cyclase.

    More Related Videos

    Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess07:35

    Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess

    Published on: June 1, 2022

    Cholinergic Ligand–dependent Modulation of Oxidative Phosphorylation Coupling in Digitonin-permeabilized BE(2)-C Neuroblastoma Cells14:39

    Cholinergic Ligand–dependent Modulation of Oxidative Phosphorylation Coupling in Digitonin-permeabilized BE(2)-C Neuroblastoma Cells

    Published on: April 28, 2026

    Related Concept Videos

    ATP Synthase: Mechanism01:48

    ATP Synthase: Mechanism

    In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
    Introduction to Mechanisms of Enzyme Catalysis01:13

    Introduction to Mechanisms of Enzyme Catalysis

    For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild...
    Activation and Inactivation of G Proteins01:22

    Activation and Inactivation of G Proteins

    Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
    GPCRs Regulate Adenylyl Cylase Activity01:09

    GPCRs Regulate Adenylyl Cylase Activity

    Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
    Two...
    cAMP-dependent Protein Kinase Pathways01:25

    cAMP-dependent Protein Kinase Pathways

    Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
    Calmodulin-dependent Signaling01:16

    Calmodulin-dependent Signaling

    Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
    The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...