5-oxoprolinase

5-oxoprolinase (OPLAH) is a cytoplasmic enzyme that catalyzes the ATP-dependent cleavage of 5-oxo-L-proline to L-glutamate, a reaction involved in amino acid metabolism and glutathione homeostasis (UniProt: O14841). The enzyme is expressed broadly across tissues and plays a housekeeping role in preventing accumulation of 5-oxoproline, a byproduct of γ-glutamyl cycle activity. Pathogenic variants cause 5-oxoprolinase deficiency (OPLAHD), characterized by urolithiasis and gastrointestinal dysfunction due to excessive urinary 5-oxoproline.

In Alzheimer's Disease, OPLAH protein abundance is increased in post-mortem human AD brain tissue compared to age-matched controls (mean log2 fold-change: +0.8488, Chaparral AD proteomics). This upregulation was detected in TMT-labeled quantitative proteomic analysis of multiple subcellular fractions from affected brain regions. The elevation may reflect altered glutamate metabolism or compensatory responses to excitotoxic stress characteristic of neurodegeneration, though the functional consequence of increased 5-oxoprolinase in AD pathology requires further investigation.