Accepted Article
DR. PHILIP WESLEY WERTZ (Orcid ID : 0000-0002-2829-5475)
Article type
: Review Article Naturally Occurring ω-Hydroxyacids.
Philip W. Wertz 1412 Laurel Street Iowa City IA 52242
319-337-4364 [email protected]
Key words: chemical analysis, skin barrier, skin physiology/structure, glucosylceramide, ceramide
ABSTRACT ω-Hydroxyacids are fatty acids bearing a hydroxyl group on the terminal carbon. They are found in mammals and higher plants and are often involved in providing a permeability barrier, the primary purpose of which is to reduce water loss. Some ω-hydroxyacid derivatives may be involved in water proofing and signaling. The purpose of this review is to survey the known natural sources of ωhydroxyacids. ω -Hydroxyacids are produced by two different P450-dependent mechanisms. The longer (30 – 34 carbons) ω-hydroxyacids are produced by chain extension from palmitic acid until the chain extends across the membrane in which the extension is taking place, and then the terminal carbon is hydroxylated. Shorter fatty acids can be hydroxylated directly to produce C16 and C18 ωhydroxyacids found in plants and 20-eicosatetraenoic acid (20-HETE) by a different P450. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/ics.12432 This article is protected by copyright. All rights reserved.
Accepted Article
The C16 and C18 ω-hydroxyacids are components of polymers in plants. The long-chain ωhydroxyacids are found in epidermal sphingolipids, in giant ring lactones from the sebum of members of the equidae, as a component of meibum and in carnauba wax and wool wax.
MAMMALIAN EPIDERMAL SPHINGOLIPIDS Mammalian epidermis contains an unusual glucosylceramide consisting of a long-chain sphingoid base with an amide linked ω-hydroxyacid bearing linoleic acid ester-linked to the ω-hydroxyl group [1,2]. Glucose is β-glycosidically-linked to the primary hydroxyl group of the sphingoid base. The base component may be sphingosione, dihydrosphingosine, phytosphingosine or 6hydroxysphingosine. In the human, all of these bases are present [3]. In pig epidermis the longchain base component of this sphingolipid consists of a mixture of sphingosine and dihydrosphingosines [1]. Epidermal acylglucosylceramides are associated with lamellar granules [4,5]. Roughly two thirds of the lamellar granule-associated acylglucosylceramide is in the bounding membrane of the granule while one third is associated with the internal lamellae [5]. The acylglucosylceramides in the bounding membrane are oriented with the glucose on the inner side [6]. The acylglucosylceramides of the internal lamellae of the lamellar granule are precursors of analogous acylceramides found in the stratum corneum [7]. The acylglucosylceramides in the bounding membrane of the lamellar granule are precursors of the ω-hydroxyceramides which are covalently attached to the outer surface of the cornified envelopes in the stratum corneum [8]. This relationship is illustrated in Fig. 1. When the bounding membrane of the lamellar granule fuses into the cell plasma membrane, the orientation of the acylglucosylceramide becomes inverted. There are two stereoselective lipoxygenase attacks on the linoleate, and the oxygenated linoleate is removed [9]. The resulting ω-hydroxyglucosylceramides becomes ester-linked to acidic amino acid
This article is protected by copyright. All rights reserved.
Accepted Article
side chains at the surface of the nascent cornified envelope, and this reaction may be catalyzed by a transglutaminase [10]. After glucosylceramide is attached to the envelope, the glucose is removed through action of a glucocerebrosidase [11-13]. The covalently bound lipid layer may provide a template upon which the intercellular free lipid layers form, and it may play a role in cohesion in the stratum corneum [14]. The acylceramides in the stratum corneum play an essential role in organization of the intercellular lipids to form a permeability barrier. These molecules have been shown to be essential for formation of the 13 nm broad-narrow-broad repeating pattern seen in transmission electron micrographs when ruthenium tetroxide is used in fixation of stratum corneum lipids as well as the 13 nm periodicity seen in X-ray diffraction [15,16]. These ω-hydroxyacids in the acylglucosylceramide and the related acylceramide are predominantly straight-chained saturates (58%) with smaller proportions of monounsaturates (35%) and dienes (7%). The chain lengths of each series range from 20 through 34 carbons with the most abundant species being C30:0, C32:1 and C34:2. Consistant with the previous statement that these long ω-hydroxyacids are produced by chain extension until the chain spans a membrane followed by hydroxylation by a P450, these major species are all 3.6 nm in length, which corresponds to the thickness of a typical mammalian bilayer. The presence of ω-hydroxyacids in hydrolyzed wool wax may be attributed to epidermal acylceramide and possibly ω-hydroxyceramide [17]. MEIBUM [18-20] Specialized sebaceous glands along the edge of the eyelids produce a lipid mixture which flows over the surface of the eye and limits the rate at which water can evaporate from the surface and also provides protection against microorganisms. This lipid mixture is called meibum. One of the meibomian lipids has been identified as consisting of ω-hydroxyacids with a fatty acid ester-linked to
This article is protected by copyright. All rights reserved.
Accepted Article
the ω-hydroxyl group and a sterol ester-linked to the carboxylate of the ω-hydroxyacid [20]. The ester-linked fatty acids were said to be short with some anteiso branched chains and with C18:1 predominating. The sterol component included cholesterol (60%), Δ7 cholestenol (35%) and an unidentified component (5%). The ω-hydroxyacids in the lipid were said to be in the range of C29C38. In humans, various forms of dry eye are attributed to meibomian gland disfunction. EQUINE SEBUM Species within the genus Equus produce sebum with giant-ring lactones as a major component [21,22]. The ω -hydroxyacids obtained by hydrolysis of the lactones from the common horse (E. caballus) are predominantly monounsaturated, iso branched and have 33, 35 and 37 carbons in the major entities. An example is shown in Fig. 2. The lactones from other species within Equus differ in terms of saturation and iso methyl branching. The donkey (Equus asinus) produces predominantly straight unbranched chains. Interestingly, the mule (Equus asinul/caballus) contains a nearly 50-50 mixture of straight chains and iso-branched chains. It has been speculated that the equine lactones may serve as a herding pheromone. This concept is somewhat supported by the pheromone of the civet cat, civetone. However, the equine lactones are significantly higher in molecular weight than civetone, which would reduce volatility. This raises some question about potential for pheromonal activity.
20-HETE 20-HETE is a bioactive metabolite of arachidonic acid produced by action of a P450 enzyme. Reduction of 20-HETE production in the kidney or vascular overproduction of 20-HETE is associated with hypertension [23].
This article is protected by copyright. All rights reserved.
Accepted Article
CARNAUBA WAX Hydrolyzed carnauba wax consists of a complex mixture of n-alcanols, α, ω-alkanediols, nalkanoic acids and ω-hydroxyalkanoic acids [24] The ω-hydroxyacids ranged from 16 through 34 carbons, but the 24-, 26, and 28-carbon species predominate.
PLANT CUTICLE Cutin is a hydrophobic polymer that is a major part of the cuticle on the aerial epidermis. This polymer is imbedded with waxes and hydrocarbons to provide a water barrier. Cutin contains C16 and C18 ω-hydroxyacids [25]. SUBERIN Suberin is a biopolymer that serves protective functions in plant tissue. Suberin is found in the periderm of bark and roots [26,27]. Like cutin, this biopolymer contain C16 and C18 ω-hydroxyacids.
REFERENCES 1.
Wertz, P.W. and Downing, D.T. Acylglucosylceramides of pig epidermis: structure determination. J Lipid Res 24, 753-758 (1983)
2. Abraham, W., Wertz, P.W. and Downing, D.T. Linoleate-rich acylglucosylceramides of pig epidermis: structure determination by proton magnetic resonance. J Lipid Res 26:761-766 (1985) 3. Ponec, M., Weerheim, A., Lankhorst, .P and Wertz, P.W. New acylceramide in native and reconstructed epidermis. J Invest Dermatol 120, 581-588 (2003) 4. Wertz, P.W., Downing, D.T., Freinkel. R.K. and Traczyk, T.N. Sphingolipids of the stratum corneum and lamellar granules of fetal rat epidermis. J Invest Dermatol 83, 193- 195 (1984)
This article is protected by copyright. All rights reserved.
Accepted Article
5. Madison, K.C., Sando, G.N., Howard, E.J., True, C.A., Gilbert, D., Swartzendruber, D.C. and Wertz, P.W. Lamellar granule biogenesis: Glucosyltransferase, lysiosomal enzyme transport, and the golgi. J Invest Derm Symp Proc 3, 80-86 (1998) 6. Wertz, P.W. Lipids and barrier function of the skin [Acta Derm Veneriol Suppl 208, 7-11 (2000) 7. Wertz, P.W. and Downing, D.T. Ceramides of pig epidermis: structure determination. J Lipid Res 24, 759-765 (1983) 8. Wertz, P.W. and Downing, D.T. Covalently bound ω-hydroxyacylsphingosine in the stratum corneum. Biochim Biophys Acta 917, 108-111 (1987) 9. Zheng, Y., Lin, H., Boeglin, W.E., Elias, P.M., Crumrine, D., Beier, D.R. and Brash, A.R. Lipoxygenases mediate the effect of essential fatty acid in skin barrier formation. J Biol Chem 286, 24046-24056 (2011) 10. Nemes, Z., Marekov, L.N., Fesus, L. and Steinert, P.M. A novel function for transglutaminase 1: attachment of long-chain omega-hydroxyceramides to involucrin be ester bond formation. Proc Nat Acad Sci USA 96, 8402-8407 (1999) 11. Chan, A., Hollerin, W.M., Ferguson, T., Crumrine, D., Goker-Alpan, O., Schiffmann, R., Tayebi, N., Ginns, E.I., Elias, P.M. and Sidransky, E. Skin ultrastructural findings in type 2 Gaucher disease: diagnostic implications. Mol Genet Metab 104, 631-636 (2011) 12. Yoshida, N., Sawada, E. and Imokawa, G. A reconstructed human epidermal keratinization culture model to characterize ceramide metabolism in the stratum corneum. Arch Derm Res 304, 563-577 (2012) 13. Borkowski, A.W., Park, K., Uchida, Y. and Gallo, R.L. Activation of TLR3 in keratinocytes increases expression of genes involved in formation of the epidermis, lipid accumulation and epidermal organelles. J Invest Dermatol 133, 2031-2040 (2013)
This article is protected by copyright. All rights reserved.
Accepted Article
14. Wertz, P.W., Swartzendruber, D.C., Kitko, D.J., Madison. K.C. and Downing, D.T. The role of the corneocyte lipid envelopes in cohesion of the stratum corneum. J Invest Dermatol 93, 169-172 (1989) 15. Kuempel, D., Swartzendruber, D.C., Squier, C.A. and Wertz, P.W. In vitro reconstitution of stratum corneum lipid lamellae. Biochim Biophys Acta 1372, 135-140 (1998) 16. de Jager, M.W., Gooris, G.S., Dolbnya, I.P. Ponec, M. and Bouwstra, J.A. Modeling the stratum corneum lipid organization with synthetic lipid mixtures: the importance of synthetic ceramide composition. Biochim Biophys Acta 1664, 132-140 (2004) 17. Downing, D.T., Kranz, Z.H. and Murray, K.E. Studies in waxes XIV. An investigation of the aliphatic constituents of hydrolyzed wool wax by gas chromatography. Aust J Chem 13, 8094 (1960) 18. Nicolaides, N., Santos, E.C., Papadakis, K., Ruth, E.C. and Muller, L. The occuerence of long chain alpha, omega-diols in the lipids of steer and human Meibomian glands. Lipids 19:990993, 1984 19. Nicolaides N, Santos EC: The di- and triesters of the lipids of steer and human Meibomian glands. Lipids 20, 454-467 (1985) 20. Butovich, I.A., McMahon, A., Wojtowicz, J.C., Feng, L., Mancini, R. and Itani, K. Dissecting lipid metabolism in Meibomian glands of human and mice: An integrative study reveals a network of metabolic reactions not duplicated in other tissues. Biochim Biophys Acta 1861, 538-553 (2016) 21. Downing, D.T. and Colton, S.W. Skin surface lipids of the horse. Lipids 15, 323-327 (1980) 22. Colton, S.W. and Downing, D.T. Variation in skin surface lipid composition among the equidae. Comp Biochem Physiol 75B, 429-433 (1983) 23. Maldman, M., Peterson, S.J., Arad, M. and Hochhauser, E. The role of 20-HETE in cardiovascular diseases and its risk factors Prostaglandins & other Lipid Mediators 125, 108117 (2016)
This article is protected by copyright. All rights reserved.
Accepted Article
24. Downing, D.T., Kranz, Z.H. and Murray, K.E. Studies in waxes XX. The quantitative analysis of hydrolyzed Carnauba wax by gas chromatography. Aust J Chem 14, 619-627 (1961) 25. Fernandez, V., Guzman-Delgado, P., Graca, J., Santos, S. and Gil, L. Cuticle structure in relation to chemical composition: Re-assessing the prevailing model. Front Pland Sci 7, 427 (2016) 26. Santos, S., Cabral, V. and Graca, J. Cork suberin molecular structure: stereochemistry of the C18 epoxy and vic-diol ω-hydroxyacids and alfa- ω-diacids analyzed by NMR. J Agric Food Chem 61, 7038-7047 (2013) 27. Graca, J. Suberin: the biopolymer at the frontier of plants. Front Chem 3:62-75, 2015
FIGURE LEGENDS Figure 1. Lamellar granule-associated acylglucosylceramide serves as the precursor to acylceramide in the stratum corneum and the covalently bound ceramide at the surface of the cornified envelope. Acylglucosylceramide in the bounding membrane of the lamellar granule is the precursor of the covalently bound ceramide, while acylglucosylceramide from the internal lamellae of the lamellar granule is converted to acylceramide.
Figure 2. Structure of a lactone. In the most abundant giant-ring lactone froom Equus caballus x+y = 28.
This article is protected by copyright. All rights reserved.
Accepted Article
DR. PHILIP WESLEY WERTZ (Orcid ID : 0000-0002-2829-5475)
Article type
: Review Article Naturally Occurring ω-Hydroxyacids.
Philip W. Wertz 1412 Laurel Street Iowa City IA 52242
319-337-4364 [email protected]
Key words: chemical analysis, skin barrier, skin physiology/structure, glucosylceramide, ceramide
ABSTRACT ω-Hydroxyacids are fatty acids bearing a hydroxyl group on the terminal carbon. They are found in mammals and higher plants and are often involved in providing a permeability barrier, the primary purpose of which is to reduce water loss. Some ω-hydroxyacid derivatives may be involved in water proofing and signaling. The purpose of this review is to survey the known natural sources of ωhydroxyacids. ω -Hydroxyacids are produced by two different P450-dependent mechanisms. The longer (30 – 34 carbons) ω-hydroxyacids are produced by chain extension from palmitic acid until the chain extends across the membrane in which the extension is taking place, and then the terminal carbon is hydroxylated. Shorter fatty acids can be hydroxylated directly to produce C16 and C18 ωhydroxyacids found in plants and 20-eicosatetraenoic acid (20-HETE) by a different P450. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/ics.12432 This article is protected by copyright. All rights reserved.
Accepted Article
The C16 and C18 ω-hydroxyacids are components of polymers in plants. The long-chain ωhydroxyacids are found in epidermal sphingolipids, in giant ring lactones from the sebum of members of the equidae, as a component of meibum and in carnauba wax and wool wax.
MAMMALIAN EPIDERMAL SPHINGOLIPIDS Mammalian epidermis contains an unusual glucosylceramide consisting of a long-chain sphingoid base with an amide linked ω-hydroxyacid bearing linoleic acid ester-linked to the ω-hydroxyl group [1,2]. Glucose is β-glycosidically-linked to the primary hydroxyl group of the sphingoid base. The base component may be sphingosione, dihydrosphingosine, phytosphingosine or 6hydroxysphingosine. In the human, all of these bases are present [3]. In pig epidermis the longchain base component of this sphingolipid consists of a mixture of sphingosine and dihydrosphingosines [1]. Epidermal acylglucosylceramides are associated with lamellar granules [4,5]. Roughly two thirds of the lamellar granule-associated acylglucosylceramide is in the bounding membrane of the granule while one third is associated with the internal lamellae [5]. The acylglucosylceramides in the bounding membrane are oriented with the glucose on the inner side [6]. The acylglucosylceramides of the internal lamellae of the lamellar granule are precursors of analogous acylceramides found in the stratum corneum [7]. The acylglucosylceramides in the bounding membrane of the lamellar granule are precursors of the ω-hydroxyceramides which are covalently attached to the outer surface of the cornified envelopes in the stratum corneum [8]. This relationship is illustrated in Fig. 1. When the bounding membrane of the lamellar granule fuses into the cell plasma membrane, the orientation of the acylglucosylceramide becomes inverted. There are two stereoselective lipoxygenase attacks on the linoleate, and the oxygenated linoleate is removed [9]. The resulting ω-hydroxyglucosylceramides becomes ester-linked to acidic amino acid
This article is protected by copyright. All rights reserved.
Accepted Article
side chains at the surface of the nascent cornified envelope, and this reaction may be catalyzed by a transglutaminase [10]. After glucosylceramide is attached to the envelope, the glucose is removed through action of a glucocerebrosidase [11-13]. The covalently bound lipid layer may provide a template upon which the intercellular free lipid layers form, and it may play a role in cohesion in the stratum corneum [14]. The acylceramides in the stratum corneum play an essential role in organization of the intercellular lipids to form a permeability barrier. These molecules have been shown to be essential for formation of the 13 nm broad-narrow-broad repeating pattern seen in transmission electron micrographs when ruthenium tetroxide is used in fixation of stratum corneum lipids as well as the 13 nm periodicity seen in X-ray diffraction [15,16]. These ω-hydroxyacids in the acylglucosylceramide and the related acylceramide are predominantly straight-chained saturates (58%) with smaller proportions of monounsaturates (35%) and dienes (7%). The chain lengths of each series range from 20 through 34 carbons with the most abundant species being C30:0, C32:1 and C34:2. Consistant with the previous statement that these long ω-hydroxyacids are produced by chain extension until the chain spans a membrane followed by hydroxylation by a P450, these major species are all 3.6 nm in length, which corresponds to the thickness of a typical mammalian bilayer. The presence of ω-hydroxyacids in hydrolyzed wool wax may be attributed to epidermal acylceramide and possibly ω-hydroxyceramide [17]. MEIBUM [18-20] Specialized sebaceous glands along the edge of the eyelids produce a lipid mixture which flows over the surface of the eye and limits the rate at which water can evaporate from the surface and also provides protection against microorganisms. This lipid mixture is called meibum. One of the meibomian lipids has been identified as consisting of ω-hydroxyacids with a fatty acid ester-linked to
This article is protected by copyright. All rights reserved.
Accepted Article
the ω-hydroxyl group and a sterol ester-linked to the carboxylate of the ω-hydroxyacid [20]. The ester-linked fatty acids were said to be short with some anteiso branched chains and with C18:1 predominating. The sterol component included cholesterol (60%), Δ7 cholestenol (35%) and an unidentified component (5%). The ω-hydroxyacids in the lipid were said to be in the range of C29C38. In humans, various forms of dry eye are attributed to meibomian gland disfunction. EQUINE SEBUM Species within the genus Equus produce sebum with giant-ring lactones as a major component [21,22]. The ω -hydroxyacids obtained by hydrolysis of the lactones from the common horse (E. caballus) are predominantly monounsaturated, iso branched and have 33, 35 and 37 carbons in the major entities. An example is shown in Fig. 2. The lactones from other species within Equus differ in terms of saturation and iso methyl branching. The donkey (Equus asinus) produces predominantly straight unbranched chains. Interestingly, the mule (Equus asinul/caballus) contains a nearly 50-50 mixture of straight chains and iso-branched chains. It has been speculated that the equine lactones may serve as a herding pheromone. This concept is somewhat supported by the pheromone of the civet cat, civetone. However, the equine lactones are significantly higher in molecular weight than civetone, which would reduce volatility. This raises some question about potential for pheromonal activity.
20-HETE 20-HETE is a bioactive metabolite of arachidonic acid produced by action of a P450 enzyme. Reduction of 20-HETE production in the kidney or vascular overproduction of 20-HETE is associated with hypertension [23].
This article is protected by copyright. All rights reserved.
Accepted Article
CARNAUBA WAX Hydrolyzed carnauba wax consists of a complex mixture of n-alcanols, α, ω-alkanediols, nalkanoic acids and ω-hydroxyalkanoic acids [24] The ω-hydroxyacids ranged from 16 through 34 carbons, but the 24-, 26, and 28-carbon species predominate.
PLANT CUTICLE Cutin is a hydrophobic polymer that is a major part of the cuticle on the aerial epidermis. This polymer is imbedded with waxes and hydrocarbons to provide a water barrier. Cutin contains C16 and C18 ω-hydroxyacids [25]. SUBERIN Suberin is a biopolymer that serves protective functions in plant tissue. Suberin is found in the periderm of bark and roots [26,27]. Like cutin, this biopolymer contain C16 and C18 ω-hydroxyacids.
REFERENCES 1.
Wertz, P.W. and Downing, D.T. Acylglucosylceramides of pig epidermis: structure determination. J Lipid Res 24, 753-758 (1983)
2. Abraham, W., Wertz, P.W. and Downing, D.T. Linoleate-rich acylglucosylceramides of pig epidermis: structure determination by proton magnetic resonance. J Lipid Res 26:761-766 (1985) 3. Ponec, M., Weerheim, A., Lankhorst, .P and Wertz, P.W. New acylceramide in native and reconstructed epidermis. J Invest Dermatol 120, 581-588 (2003) 4. Wertz, P.W., Downing, D.T., Freinkel. R.K. and Traczyk, T.N. Sphingolipids of the stratum corneum and lamellar granules of fetal rat epidermis. J Invest Dermatol 83, 193- 195 (1984)
This article is protected by copyright. All rights reserved.
Accepted Article
5. Madison, K.C., Sando, G.N., Howard, E.J., True, C.A., Gilbert, D., Swartzendruber, D.C. and Wertz, P.W. Lamellar granule biogenesis: Glucosyltransferase, lysiosomal enzyme transport, and the golgi. J Invest Derm Symp Proc 3, 80-86 (1998) 6. Wertz, P.W. Lipids and barrier function of the skin [Acta Derm Veneriol Suppl 208, 7-11 (2000) 7. Wertz, P.W. and Downing, D.T. Ceramides of pig epidermis: structure determination. J Lipid Res 24, 759-765 (1983) 8. Wertz, P.W. and Downing, D.T. Covalently bound ω-hydroxyacylsphingosine in the stratum corneum. Biochim Biophys Acta 917, 108-111 (1987) 9. Zheng, Y., Lin, H., Boeglin, W.E., Elias, P.M., Crumrine, D., Beier, D.R. and Brash, A.R. Lipoxygenases mediate the effect of essential fatty acid in skin barrier formation. J Biol Chem 286, 24046-24056 (2011) 10. Nemes, Z., Marekov, L.N., Fesus, L. and Steinert, P.M. A novel function for transglutaminase 1: attachment of long-chain omega-hydroxyceramides to involucrin be ester bond formation. Proc Nat Acad Sci USA 96, 8402-8407 (1999) 11. Chan, A., Hollerin, W.M., Ferguson, T., Crumrine, D., Goker-Alpan, O., Schiffmann, R., Tayebi, N., Ginns, E.I., Elias, P.M. and Sidransky, E. Skin ultrastructural findings in type 2 Gaucher disease: diagnostic implications. Mol Genet Metab 104, 631-636 (2011) 12. Yoshida, N., Sawada, E. and Imokawa, G. A reconstructed human epidermal keratinization culture model to characterize ceramide metabolism in the stratum corneum. Arch Derm Res 304, 563-577 (2012) 13. Borkowski, A.W., Park, K., Uchida, Y. and Gallo, R.L. Activation of TLR3 in keratinocytes increases expression of genes involved in formation of the epidermis, lipid accumulation and epidermal organelles. J Invest Dermatol 133, 2031-2040 (2013)
This article is protected by copyright. All rights reserved.
Accepted Article
14. Wertz, P.W., Swartzendruber, D.C., Kitko, D.J., Madison. K.C. and Downing, D.T. The role of the corneocyte lipid envelopes in cohesion of the stratum corneum. J Invest Dermatol 93, 169-172 (1989) 15. Kuempel, D., Swartzendruber, D.C., Squier, C.A. and Wertz, P.W. In vitro reconstitution of stratum corneum lipid lamellae. Biochim Biophys Acta 1372, 135-140 (1998) 16. de Jager, M.W., Gooris, G.S., Dolbnya, I.P. Ponec, M. and Bouwstra, J.A. Modeling the stratum corneum lipid organization with synthetic lipid mixtures: the importance of synthetic ceramide composition. Biochim Biophys Acta 1664, 132-140 (2004) 17. Downing, D.T., Kranz, Z.H. and Murray, K.E. Studies in waxes XIV. An investigation of the aliphatic constituents of hydrolyzed wool wax by gas chromatography. Aust J Chem 13, 8094 (1960) 18. Nicolaides, N., Santos, E.C., Papadakis, K., Ruth, E.C. and Muller, L. The occuerence of long chain alpha, omega-diols in the lipids of steer and human Meibomian glands. Lipids 19:990993, 1984 19. Nicolaides N, Santos EC: The di- and triesters of the lipids of steer and human Meibomian glands. Lipids 20, 454-467 (1985) 20. Butovich, I.A., McMahon, A., Wojtowicz, J.C., Feng, L., Mancini, R. and Itani, K. Dissecting lipid metabolism in Meibomian glands of human and mice: An integrative study reveals a network of metabolic reactions not duplicated in other tissues. Biochim Biophys Acta 1861, 538-553 (2016) 21. Downing, D.T. and Colton, S.W. Skin surface lipids of the horse. Lipids 15, 323-327 (1980) 22. Colton, S.W. and Downing, D.T. Variation in skin surface lipid composition among the equidae. Comp Biochem Physiol 75B, 429-433 (1983) 23. Maldman, M., Peterson, S.J., Arad, M. and Hochhauser, E. The role of 20-HETE in cardiovascular diseases and its risk factors Prostaglandins & other Lipid Mediators 125, 108117 (2016)
This article is protected by copyright. All rights reserved.
Accepted Article
24. Downing, D.T., Kranz, Z.H. and Murray, K.E. Studies in waxes XX. The quantitative analysis of hydrolyzed Carnauba wax by gas chromatography. Aust J Chem 14, 619-627 (1961) 25. Fernandez, V., Guzman-Delgado, P., Graca, J., Santos, S. and Gil, L. Cuticle structure in relation to chemical composition: Re-assessing the prevailing model. Front Pland Sci 7, 427 (2016) 26. Santos, S., Cabral, V. and Graca, J. Cork suberin molecular structure: stereochemistry of the C18 epoxy and vic-diol ω-hydroxyacids and alfa- ω-diacids analyzed by NMR. J Agric Food Chem 61, 7038-7047 (2013) 27. Graca, J. Suberin: the biopolymer at the frontier of plants. Front Chem 3:62-75, 2015
FIGURE LEGENDS Figure 1. Lamellar granule-associated acylglucosylceramide serves as the precursor to acylceramide in the stratum corneum and the covalently bound ceramide at the surface of the cornified envelope. Acylglucosylceramide in the bounding membrane of the lamellar granule is the precursor of the covalently bound ceramide, while acylglucosylceramide from the internal lamellae of the lamellar granule is converted to acylceramide.
Figure 2. Structure of a lactone. In the most abundant giant-ring lactone froom Equus caballus x+y = 28.
This article is protected by copyright. All rights reserved.
Accepted Article
