Nucleotide Inhibition of Glyoxalase II

Nucleotide Inhibition of Glyoxalase II

Date: May 1999
Creator: Gillis, Glen S
Description: The glyoxalase system mediates the conversion of methylglyoxal, a toxic ketoaldehyde, to D-lactic acid. The system is composed of two enzymes, glyoxalase I (Glo-I) and glyoxalase II (Glo-II), and exhibits an absolute requirement for a catalytic quantity of glutathione (GSH). Glo-I catalyzes the isomerization of a hemithioacetal, formed non-enzymatically from methylglyoxal and GSH, to the corresponding a -D-hydroxyacid thioester, s-D-lactoylglutathione (SLG). Glo-II catalyzes the irreversible breakdown of SLG to D-lactate and GSH. We have observed that ATP or GTP significantly inhibits the Glo-II activity of tissue homogenates from various sources. We have developed a rapid, one step chromatography procedure to purify Glo-II such that the purified enzyme remains "sensitive" to inhibition by ATP or GTP (Glo-II-s). Studies indicate that inhibition of Glo-II-s by nucleotides is restricted to ATP, GTP, ADP, and GDP, with ATP appearing most effective. Kinetics studies have shown that ATP acts as a partial non-competitive inhibitor of Glo-II-s activity, and further suggest that two kinetically distinguishable forms of the enzyme exist. The sensitivity of pure Glo-II-s to nucleotide inhibition is slowly lost on storage even at -80° C. This loss is accelerated at higher temperatures or in the presence of ATP. Kinetics studies on the resultant "insensitive" ...
Contributing Partner: UNT Libraries
Valine 44 and Valine 45 of Human Glutiathione Sythetase are Key for Subunit Stability and Negative Cooperativity

Valine 44 and Valine 45 of Human Glutiathione Sythetase are Key for Subunit Stability and Negative Cooperativity

Date: July 8, 2011
Creator: Slavens, Kerri D.; Brown, Teresa R.; Barakat, Khaldoon A.; Cundari, Thomas R., 1964- & Anderson, Mary E.
Description: Article discussing Valine 44 and Valine 45 of human glutathione synthetase as the key for subunit stability and negative cooperativity.
Contributing Partner: UNT College of Arts and Sciences
ASPARTATE 458 of Human Glutathione Synthetase is Important for Cooperativity and Active Site Structure

ASPARTATE 458 of Human Glutathione Synthetase is Important for Cooperativity and Active Site Structure

Date: August 5, 2011
Creator: Brown, Teresa R.; Drummond, Michael L.; Barelier, Sarah; Crutchfield, Amanda S.; Dinescu, Adriana; Slavens, Kerri D. et al.
Description: Article discussing ASPARTATE 458 of human glutathione synthetase.
Contributing Partner: UNT College of Arts and Sciences
The Role of the Glycine Triad in Human Glutathione Synthetase

The Role of the Glycine Triad in Human Glutathione Synthetase

Date: October 1, 2010
Creator: Dinescu, Adriana; Brown, Teresa R.; Barelier, Sarah; Cundari, Thomas R., 1964- & Anderson, Mary E.
Description: Article discussing the role of the glycine triad in human glutathione synthetase.
Contributing Partner: UNT College of Arts and Sciences