Disease relevance of Oplah

• Thus, administration of L-2-oxothiazolidine-4-carboxylate protected against acetaminophen toxicity in mice; the thiazolidine, which is converted to L-cysteine by the enzyme 5-oxo-L-prolinase (present in many animal tissues and in plants) promotes the synthesis of glutathione, which is the actual protectant [1].

High impact information on Oplah

• Stimulation of hepatic glutathione formation by administration of L-2-oxothiazolidine-4-carboxylate, a 5-oxo-L-prolinase substrate [2].
• 5-Oxo-L-prolinase, the enzyme that catalyzes the conversion of 5-oxo-L-proline to L-glutamate coupled to the cleavage of ATP to ADP and Pi, also acts on L-2-oxothiazolidine-4-carboxylate (an analog of 5-oxoproline in which the 4-methylene moiety is replaced by sulfur) and ATP to yield cysteine and ADP [2].
• The function of the gamma-glutamyl cycle was explored in in vivo studies in which amino acids and specific inhibitors of cycle enzymes (gamma-glutamyl transpeptidase, gamma-glutamyl cyclotransferase, gamma-glutamylcysteine synthetase, and 5-oxoprolinase) were administered to mice [3].
• It is converted intracellularly by the action of 5-oxoprolinase into L-cysteine [4].
• Localization of 5-oxo-L-prolinase mRNA in the murine choroid plexus by in situ hybridization [5].

Anatomical context of Oplah

• Expression of 5-OPase mRNA was found in epithelial cells of the proximal tubules in kidney as well as in the epithelium and vascular endothelial cells of the choroid plexus but not in periventricular capillaries [5].

Associations of Oplah with chemical compounds

• L-2-oxothiazolidine-4-carboxylate thus serves as a potent inhibitor of the gamma-glutamyl cycle at the step of 5-oxoprolinase [2].

Analytical, diagnostic and therapeutic context of Oplah

• In the present study we investigated the expression of 5-oxo-L-prolinase, an enzyme of this pathway, in mouse brain and kidney by in situ hybridization using digoxygenin-labeled RNA probes [5].

References