Keratinocyte ceramide biosynthesis pathway

The keratinocyte ceramide biosynthesis pathway is a critical metabolic process in the epidermis responsible for the production of ceramides, the primary lipid constituents of the stratum corneum's extracellular matrix. This pathway involves several key enzymes, including serine palmitoyltransferase (SPT), ceramide synthase (CerS), and acid sphingomyelinase, which work through de novo synthesis, sphingomyelin hydrolysis, and salvage routes to maintain skin barrier integrity (Uchida & Park, 2021). Ceramides are essential for preventing transepidermal water loss and protecting the body from environmental insults and microbial invasion. Deficiencies or alterations in the composition of ceramides within this pathway are strongly linked to the pathogenesis of inflammatory skin diseases such as atopic dermatitis and psoriasis (Holleran et al., 2006). Pharmacological intervention typically aims to enhance this pathway using PPAR agonists or niacinamide to boost endogenous production, or by applying topical ceramide formulations to compensate for losses (Mizutani et al., 2009). Conversely, inhibitors of this pathway are primarily used in research to study sphingolipid signaling and its role in cell death and differentiation.

Other names

Epidermal ceramide synthesisSphingolipid metabolism in keratinocytesDe novo ceramide synthesis pathway

Transcriptional upregulation of biosynthetic enzymes via PPAR activation; direct inhibition of rate-limiting enzymes like serine palmitoyltransferase; exogenous lipid supplementation.