Lysosomal acid hydrolases (LAH)

Lysosomal acid hydrolases represent a large group of approximately 60 enzymes sequestered within the lysosome that are responsible for the controlled degradation of biological polymers such as proteins, nucleic acids, lipids, and complex carbohydrates. These enzymes exhibit optimal catalytic activity at the acidic pH (4.5–5.0) maintained within the lysosomal lumen, a feature that protects the rest of the cell from accidental degradation should the enzymes leak into the neutral cytosol (NIH, 2023). They play a critical role in cellular recycling and waste management, facilitating processes like autophagy and the breakdown of materials internalized via endocytosis (UniProt, 2024). Genetic deficiencies in specific acid hydrolases lead to Lysosomal Storage Diseases (LSDs), such as Gaucher, Fabry, and Pompe diseases, where undigested substrates accumulate to toxic levels in various organs (StatPearls, 2023). Therapeutic interventions primarily involve enzyme replacement therapy (ERT), which supplies recombinant versions of the missing enzyme, or small molecule chaperones that assist in the proper folding of mutant enzymes. Beyond rare genetic disorders, the dysfunction of these hydrolases is increasingly implicated in the pathogenesis of common neurodegenerative conditions like Parkinson's disease and in the metabolic reprogramming of cancer cells (Nature Reviews Molecular Cell Biology, 2022). This entry is marked as incorrect because it refers to a broad functional class of enzymes rather than a single, specific molecular target.

Other names

Acid hydrolasesLysosomal enzymesVacuolar hydrolasesLysosomal hydrolases

Enzyme replacement therapy (ERT) provides exogenous functional enzymes to degrade accumulated substrates; pharmacological chaperones stabilize misfolded endogenous enzymes to improve trafficking to the lysosome; substrate reduction therapy (SRT) decreases the biosynthetic workload of the hydrolases.