Related Experiment Video
Updated: Apr 6, 2026
09:22
The Cell-based L-Glutathione Protection Assays to Study Endocytosis and Recycling of Plasma Membrane Proteins
Published on: December 13, 2013
11.0K
Membrane accessibility of glutathione
Alvaro Garcia1, Nasma D Eljack1, Marc-Antoine Sani2
1School of Chemistry, University of Sydney, Sydney, New South Wales 2006, Australia.
Biochimica Et Biophysica Acta
|August 2, 2015
Summary
Glutathione does not enter cell membranes to regulate the Na+,K+-ATPase (sodium-potassium pump). Instead, it accesses the enzyme's cysteine residue by creating a pathway between protein subunits, inhibiting its activity.
Area of Science:
- Biochemistry
- Cell Biology
- Structural Biology
Background:
- The Na+,K+-ATPase (sodium-potassium pump) is vital for animal cell survival, regulating ion transport.
- Evidence suggests glutathionylation of cysteine 45 on the β-subunit controls Na+,K+-ATPase activity.
- This cysteine residue is located within a transmembrane domain, posing questions about accessibility.
Purpose of the Study:
- To investigate the mechanism by which glutathione modifies the Na+,K+-ATPase.
- To determine if glutathione can penetrate lipid membranes to reach the target cysteine residue.
- To elucidate the structural basis for glutathione-mediated regulation of the enzyme's activity.
Main Methods:
- Fluorescence spectroscopy
- Nuclear Magnetic Resonance (NMR) spectroscopy
- Molecular dynamics simulations
Main Results:
- Glutathione was found to be unable to penetrate the interior of a lipid membrane.
- A proposed mechanism involves the loosening of the α-β subunit association.
- This loosening creates a hydrophilic passageway for glutathione access to cysteine 45.
Conclusions:
- Glutathionylation of Na+,K+-ATPase likely occurs via an inter-subunit hydrophilic channel, not direct membrane penetration.
- This modification may anchor the β-subunit, restricting motion and suppressing enzymatic activity.
- The findings suggest a structural mechanism for glutathione-mediated regulation of the Na+,K+-ATPase.
Related Concept Videos
01:22Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation
1.2K
Glutathione, a tripeptide made up of glutamate, cysteine, and glycine, is a critical player in the detoxification of drugs and xenobiotics via a process known as glutathione conjugation or mercapturic acid formation. This phase II biotransformation reaction involves the covalent binding of glutathione to a drug or its metabolite, enhancing the compound's water solubility and enabling its excretion.
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
1.2K
01:44The Significance of Membrane Transport
44.7K
The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
44.7K
01:20Sulfur Assimilation
506
Sulfur is an essential element in biological systems, contributing to synthesizing key biomolecules, including amino acids such as cysteine and methionine, and cofactors such as coenzyme A and biotin. Microorganisms primarily assimilate sulfur as sulfate (SO₄²⁻) from the environment, which must undergo a series of biochemical transformations before it can be incorporated into cellular components. As sulfate is highly oxidized, it must undergo assimilatory sulfate reduction to...
506
01:22Enlargement of the Plasma Membrane
2.7K
Cell division and enlargement are processes that require precise control. The control ensures that cell division cannot proceed unless the cell has grown to a specific size. A spherical, dividing cell requires an approximately 1.6X increase in its surface area to double its volume. The secretory pathway also has a significant role in cell membrane enlargement. Secretory vesicles that bud off from the Golgi apparatus and later fuse with the plasma membrane during exocytosis are a major source of...
2.7K
01:16Facilitated Diffusion
1.6K
The plasma membrane, a critical structure in cellular biology, houses an array of transporters, or carrier proteins, interspersed within its lipid bilayer. These proteins play a crucial role in solute transport through facilitated diffusion, a form of passive diffusion that uses transporters to move the molecules across the membrane.
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...
1.6K
01:30Membrane Proteins
31.5K
Plasma membranes have integral transmembrane proteins involved in facilitated transport. These proteins are collectively referred to as transport proteins, and they function as either channels for the material or as carriers themselves. Channel proteins have hydrophilic domains exposed to the intracellular and extracellular fluids and a hydrophilic channel through their core that provides a hydrated opening for solutes to pass through the membrane layers. Passage through the channel allows...
31.5K