Reduced Catalase Enzymatic Activity in Prostate Cancer Independent of L299F and A333T Variants

Background/Objectives: Catalase (CAT) plays a pivotal role in cellular redox homeostasis by catalyzing the decomposition of hydrogen peroxide, thereby mitigating oxidative damage. Impaired CAT function has been linked to chronic inflammation, deregulated cell proliferation, and oncogenesis. While numerous CAT variants have been reported, their functional relevance in prostate cancer (PCa) remains unclear. This study investi-gated CAT genetic variants, enzymatic activity, and potential pathogenic significance in PCa. Methods: Peripheral blood samples from 17 patients with prostate cancer (PCa) and 17 patients with benign prostatic hyperplasia (BPH) were processed for genomic DNA extraction and quantification. Reported missense variants were screened using pub-lic genomic databases. Pathogenicity was predicted with SNPs&GO, PolyPhen-2, and I-Mutant 2.0. Protein modeling was performed with UCSF Chimera, and structural quality was assessed via Ramachandran plots. Two selected variants (L299F, A333T) were geno-typed using the rhAmp™ SNP assay. Serum CAT activity was quantified spectrophoto-metrically (240 nm) following Aebi’s protocol. Results: CAT activity was significantly re-duced in PCa compared to BPH (1.44 ± 0.24 vs. 1.91 ± 0.25 U/mg protein, p = 0.033), with no association to age, PSA levels, or comorbidities. In silico predictions identified variants K177T, G216V, and L351P as potentially deleterious, while N452S appeared benign. Gen-otyping revealed that all participants were wild-type homozygous for L299F and A333T. Conclusions: PCa is characterized by diminished CAT activity independent of the inves-tigated variants, suggesting an alternative regulatory mechanism, such as epigenetic reg-ulation or post-translational modifications, may drive CAT downregulation. These find-ings support further investigation into CAT as a potential biomarker and therapeutic tar-get in oxidative stress–mediated prostate carcinogenesis.