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Review
. 2022 Jul 26;12(8):685.
doi: 10.3390/metabo12080685.

PNPLA1-Mediated Acylceramide Biosynthesis and Autosomal Recessive Congenital Ichthyosis

Fansi Zeng  1 , Wenzhen Qin  2 , Feifei Huang  1 , Pingan Chang  1
Affiliations
Review

PNPLA1-Mediated Acylceramide Biosynthesis and Autosomal Recessive Congenital Ichthyosis

Fansi Zeng et al. Metabolites. .

Abstract

The stratum corneum of the epidermis acts as a life-sustaining permeability barrier. Unique heterogeneous ceramides, especially ω-O-acylceramides, are key components for the formation of stable lamellar membrane structures in the stratum corneum and are essential for a vital epidermal permeability barrier. Several enzymes involved in acylceramide synthesis have been demonstrated to be associated with ichthyosis. The function of patatin-like phospholipase domain-containing protein 1 (PNPLA1) was a mystery until the finding that PNPLA1 gene mutations were involved in autosomal-recessive congenital ichthyosis (ARCI) patients, both humans and dogs. PNPLA1 plays an essential role in the biosynthesis of acylceramide as a CoA-independent transacylase. PNPLA1 gene mutations cause decreased acylceramide levels and impaired skin barrier function. More and more mutations in PNPLA1 genes have been identified in recent years. Herein, we describe the structural and functional specificity of PNPLA1, highlight its critical roles in acylceramide synthesis and skin barrier maintenance, and summarize the PNPLA1 mutations currently identified in ARCI patients.

Keywords: ARCI; PNPLA1; acylceramide; gene mutation; skin barrier.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Protein domains of the human PNPLA1. (A) Patatin domain (aa 16-185) and a proline-rich hydrophobic region (aa 326–451) were present in the N- and C-terminal regions, respectively. S53 and D172 represent the conserved catalytic residues of serine and aspartate in the patatin domain. (B) Molecular model of the patatin domain of human PNPLA1. Regions predicted to fold as β-sheets and α-helices are shaded yellow and green, respectively. Side chains of the active sites, Asp172 and Ser53, are rendered in stick format and the atoms colored using standard Corey, Pauling and Kultun (CPK).
Figure 2
Figure 2
Acylceramide biosynthesis pathway. Metabolites and final products are marked in blue and the catalytic enzymes of each reaction are shown in black. The ω-O-acylation prior to ceramide synthesis remains uncertain. This figure tentatively shows that ω-O-acylation occurs after ω-OH ceramide production.
See this image and copyright information in PMC

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