4-Hydroxy-2-oxoglutarate aldolase inactivity in primary hyperoxaluria type 3 and glyoxylate reductase inhibition.

摘要: Mutations in the gene encoding for 4-hydroxy-2-oxoglutarate aldolase (HOGA) are associated with an excessive production of oxalate Primary Hyperoxaluria type 3 (PH3). This enzyme is final step hydroxyproline degradation pathway within mitochondria and catalyzes cleavage (HOG) to pyruvate glyoxylate. No analyses have been performed assess consequences mutations identified, particularly those variants that produce either full-length or nearly proteins. In this study, expression, stability, activity nine PH3 human HOGA were examined. Using recombinant protein produced Escherichia coli as well transfected Chinese hamster ovary (CHO) cells, it was found all quite unstable, a tendency aggregate, retain no measurable activity. A buildup HOG confirmed urine, sera liver samples from patients. To determine how cleaved absence activity, ability N-acetylneuraminate (NAL) cleave evaluated. NAL showed minimal towards HOG. Whether expected could inhibit glyoxylate reductase (GR), mutated PH2, also GR inhibited by but not 2-hydroxyglutarate 2-oxoglutarate. Thus, one hypothetical component molecular basis appears be inhibition HOG, resulting phenotype similar PH2.