Hydrolase biosynthesis

Hydrolase biosynthesis is a multi-step biological process involving the transcription, translation, and post-translational maturation of enzymes belonging to the hydrolase class (EC 3). This process is particularly specialized for lysosomal acid hydrolases, which undergo unique modifications such as the addition of mannose 6-phosphate (M6P) tags in the Golgi apparatus to facilitate their targeting to lysosomes via specific M6P receptors [11, 12]. In the small intestine, the biosynthesis of hydrolases like lactase-phlorizin hydrolase (LPH) is a critical marker of enterocyte differentiation and is tightly regulated by transcription factors such as GATA-4 and HNF-1α [2, 9, 12]. Dysregulation or defects in the biosynthetic pathway of specific hydrolases can lead to severe pathological conditions, most notably lysosomal storage diseases (LSDs) where enzymes are either not produced, misfolded, or fail to be correctly targeted [8, 11]. Therapeutic interventions often target this process using pharmacological chaperones that stabilize nascent proteins to ensure they reach their functional cellular compartments, or gene-directed enzyme prodrug therapies (GDEPT) that introduce the biosynthetic machinery for specific hydrolases into diseased tissues [5, 6, 8]. While specific proteins within these pathways are therapeutic targets, "Hydrolase biosynthesis" refers to the overarching physiological process rather than a single molecular target.

Other names

Lysosomal hydrolase biosynthesisIntestinal hydrolase biosynthesisAcid hydrolase synthesisGlycoside hydrolase production

Pharmacological chaperones (e.g., Migalastat) bind to misfolded or unstable nascent hydrolases in the endoplasmic reticulum, stabilizing their conformation to prevent degradation and promoting their maturation and trafficking to lysosomes [8, 11]. Transcriptional regulators and epigenetic modifiers like histone methyltransferases (e.g., Dot1) or HDAC inhibitors can also modulate the expression levels of hydrolase-encoding genes [3, 4, 14].