Cytosolic beta-glucosidase (GBA3) (GBA3)

Cytosolic beta-glucosidase (GBA3) is a non-lysosomal enzyme predominantly expressed in the liver and kidney of rats, where it plays a significant role in the metabolism of various beta-D-glucosides (UniProt Q6AYK4) [1]. Unlike the lysosomal enzyme GBA1, GBA3 functions at a neutral pH and is involved in the hydrolysis of dietary flavonoids and xenobiotic glycosides, contributing to the detoxification and processing of plant-derived compounds (PubMed: 12522102) [2]. In pharmacological research, it is frequently characterized as an off-target for iminosugars and other small molecules designed to inhibit GBA1 for the treatment of Gaucher disease (PubMed: 15634793) [3]. Because GBA3 is highly active in the rat kidney, its unintended inhibition can lead to localized metabolic changes and is a key consideration in the safety assessment of glycosidase-targeting drugs (PubMed: 16150821) [4]. Understanding its interaction with potential therapeutics is crucial for predicting side effects and ensuring the selectivity of drugs intended for lysosomal targets [5]. The enzyme's broad substrate specificity allows it to process a variety of aryl- and alkyl-beta-D-glucosides, making it a versatile component of the cellular metabolic machinery [2].

Other names

Glucosylceramidase 3CBGKlotho-related proteinKLRPNeutral beta-glucosidase

Competitive inhibition of the enzyme's active site, preventing the hydrolysis of natural glucoside substrates.