Enzymes
UniProtKB help_outline | 2 proteins |
Reaction participants Show >> << Hide
- Name help_outline a (9Z,12Z)-octadecadienoyl-containing triacyl-sn-glycerol Identifier CHEBI:144774 Charge 0 Formula C23H36O6R2 SMILEShelp_outline O(C[C@@](COC(*)=O)(OC(=O)*)[H])C(*)=O 2D coordinates Mol file for the small molecule Search links Involved in 23 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline an N-(ω-hydroxy-ultra-long chain fatty acyl)-sphing-4-enine Identifier CHEBI:157663 Charge 0 Formula C20H39NO4R SMILEShelp_outline C(CCCCCCCCCC)CC\C=C\[C@@H](O)[C@@H](NC(=O)*CO)CO 2D coordinates Mol file for the small molecule Search links Involved in 13 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline a diacylglycerol Identifier CHEBI:18035 Charge 0 Formula C5H6O5R2 SMILEShelp_outline [*]OCC(CO[*])O[*] 2D coordinates Mol file for the small molecule Search links Involved in 378 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline an N-(ω-(9Z,12Z-octadecadienoyloxy)-ultra-long chain fatty acyl)-sphing-4-enine Identifier CHEBI:157662 Charge 0 Formula C38H69NO5R SMILEShelp_outline [C@H]([C@@H](/C=C/CCCCCCCCCCCCC)O)(NC(=O)*COC(CCCCCCC/C=C\C/C=C\CCCCC)=O)CO 2D coordinates Mol file for the small molecule Search links Involved in 13 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:65692 | RHEA:65693 | RHEA:65694 | RHEA:65695 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
UniProtKB help_outline |
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EC numbers help_outline |
Related reactions help_outline
Specific form(s) of this reaction
- RHEA:78012
- RHEA:78008
- RHEA:65697
- RHEA:65689
- RHEA:65685
- RHEA:65681
- RHEA:65677
- RHEA:65673
- RHEA:65669
- RHEA:65653
- RHEA:65649
More general form(s) of this reaction
Publications
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PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis.
Hirabayashi T., Anjo T., Kaneko A., Senoo Y., Shibata A., Takama H., Yokoyama K., Nishito Y., Ono T., Taya C., Muramatsu K., Fukami K., Munoz-Garcia A., Brash A.R., Ikeda K., Arita M., Akiyama M., Murakami M.
Mutations in patatin-like phospholipase domain-containing 1 (PNPLA1) cause autosomal recessive congenital ichthyosis, but the mechanism involved remains unclear. Here we show that PNPLA1, an enzyme expressed in differentiated keratinocytes, plays a crucial role in the biosynthesis of ω-O-acylceram ... >> More
Mutations in patatin-like phospholipase domain-containing 1 (PNPLA1) cause autosomal recessive congenital ichthyosis, but the mechanism involved remains unclear. Here we show that PNPLA1, an enzyme expressed in differentiated keratinocytes, plays a crucial role in the biosynthesis of ω-O-acylceramide, a lipid component essential for skin barrier. Global or keratinocyte-specific Pnpla1-deficient neonates die due to epidermal permeability barrier defects with severe transepidermal water loss, decreased intercellular lipid lamellae in the stratum corneum, and aberrant keratinocyte differentiation. In Pnpla1<sup>-/-</sup> epidermis, unique linoleate-containing lipids including acylceramides, acylglucosylceramides and (O-acyl)-ω-hydroxy fatty acids are almost absent with reciprocal increases in their putative precursors, indicating that PNPLA1 catalyses the ω-O-esterification with linoleic acid to form acylceramides. Moreover, acylceramide supplementation partially rescues the altered differentiation of Pnpla1<sup>-/-</sup> keratinocytes. Our findings provide valuable insight into the skin barrier formation and ichthyosis development, and may contribute to novel therapeutic strategies for treatment of epidermal barrier defects. << Less
Nat. Commun. 8:14609-14609(2017) [PubMed] [EuropePMC]
This publication is cited by 9 other entries.
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PNPLA1 is a transacylase essential for the generation of the skin barrier lipid omega-O-acylceramide.
Ohno Y., Kamiyama N., Nakamichi S., Kihara A.
Lipids are the primary components of the skin permeability barrier, which is the body's most powerful defensive mechanism against pathogens. Acylceramide (ω-O-acylceramide) is a specialized lipid essential for skin barrier formation. Here, we identify PNPLA1 as the long-sought gene involved in the ... >> More
Lipids are the primary components of the skin permeability barrier, which is the body's most powerful defensive mechanism against pathogens. Acylceramide (ω-O-acylceramide) is a specialized lipid essential for skin barrier formation. Here, we identify PNPLA1 as the long-sought gene involved in the final step of acylceramide synthesis, esterification of ω-hydroxyceramide with linoleic acid, by cell-based assays. We show that increasing triglyceride levels by overproduction of the diacylglycerol acyltransferase DGAT2 stimulates acylceramide production, suggesting that triglyceride may act as a linoleic acid donor. Indeed, the in vitro analyses confirm that PNPLA1 catalyses acylceramide synthesis using triglyceride as a substrate. Mutant forms of PNPLA1 found in patients with ichthyosis exhibit reduced or no enzyme activity in either cell-based or in vitro assays. Altogether, our results indicate that PNPLA1 is directly involved in acylceramide synthesis as a transacylase, and provide important insights into the molecular mechanisms of skin barrier formation and of ichthyosis pathogenesis. << Less
Nat. Commun. 8:14610-14610(2017) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.