Bouwstra J A, Gooris G S, Dubbelaar F E, Weerheim A M, Ijzerman A P, Ponec M
Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, The Netherlands.
J Lipid Res. 1998 Jan;39(1):186-96.
The main barrier of the skin is formed by the lipids in the apical skin layer, the stratum corneum (SC). In SC mainly ceramides (CER), free fatty acids (FFA) and cholesterol (CHOL) are present. The CER are composed of at least six different fractions. CER 1 has an exceptional molecular structure as it contains a linoleic acid linked to a long-chain omega-hydroxy acid (C > 30). The SC lipids are organized in two lamellar phases with periodicities of approximately 6 and 13 nm, respectively. Recent studies revealed that ceramides isolated from pig SC mixed with cholesterol in confined ratios mimic stratum corneum lipid phase behavior closely (Bouwstra, J.A., et al. 1996. J. Lipid Res. 37: 999-1011). In this paper the role of CER 1 for the SC lipid lamellar organization was studied. For this purpose lipid phase behavior of mixtures of CHOL and total ceramide fraction was compared with that of mixtures of CHOL and a ceramide mixture lacking CER 1. These studies showed that in the absence of CER 1 almost no long periodicity phase was formed over a wide CHOL/CER molar ratio. A model is proposed for the molecular arrangement of the two lamellar phases. This model is based on the dominant role CER 1 plays in the formation of the long periodicity phase, electron density distribution calculations, and observations, such as i) the bimodal distribution of the fatty acid chain lengths of the ceramides, ii) the phase separation between long-chain ceramides and short-chain ceramides in a monolayer approach, and iii) the absence of swelling of the lamellae upon increasing the water content organization in SC. In this molecular model the short periodicity phase is composed of only two high electron density regions indicating the presence of only one bilayer, similar to that often found in phospholipid membranes. The molecular arrangement in the long periodicity phase is very exceptional. This phase most probably consists of two broad and one narrow low electron density regions. The two broad regions are formed by partly interdigitating ceramides with long-chain fatty acids of approximately 24-26 C atoms, while the narrow low-electron density region is formed by fully interdigitating ceramides with a short free fatty acid chain of approximately 16 to 18 C atoms.
皮肤的主要屏障由皮肤表层即角质层（SC）中的脂质构成。在角质层中主要存在神经酰胺（CER）、游离脂肪酸（FFA）和胆固醇（CHOL）。神经酰胺至少由六种不同的组分组成。神经酰胺1具有独特的分子结构，因为它含有与长链ω-羟基酸（C>30）相连的亚油酸。角质层脂质分别以约6和13纳米的周期组织成两个片层相。最近的研究表明，从猪角质层中分离出的神经酰胺与胆固醇按特定比例混合时，能紧密模拟角质层脂质的相行为（Bouwstra, J.A., 等人，1996.《脂质研究杂志》37: 999 - 1011）。本文研究了神经酰胺1对角质层脂质片层组织的作用。为此，将胆固醇与总神经酰胺组分的混合物的脂质相行为与胆固醇和不含神经酰胺1的神经酰胺混合物的脂质相行为进行了比较。这些研究表明，在没有神经酰胺1的情况下，在较宽的胆固醇/神经酰胺摩尔比范围内几乎不会形成长周期相。提出了一个关于两个片层相分子排列的模型。该模型基于神经酰胺1在长周期相形成中所起的主导作用、电子密度分布计算以及一些观察结果，例如：i）神经酰胺脂肪酸链长度的双峰分布；ii）在单层方法中长链神经酰胺和短链神经酰胺之间的相分离；iii）在角质层中增加水分含量时片层没有膨胀。在这个分子模型中，短周期相仅由两个高电子密度区域组成，表明只存在一个双层，类似于磷脂膜中常见的情况。长周期相中的分子排列非常特殊。这个相很可能由两个宽的和一个窄的低电子密度区域组成。两个宽区域由与约24 - 26个碳原子的长链脂肪酸部分交叉排列的神经酰胺形成，而窄的低电子密度区域由与约16至18个碳原子的短游离脂肪酸链完全交叉排列的神经酰胺形成。
