PHYSICAL-CHEMICAL BEHAVIOR OF DIETARY AND BILIARY LIPIDS DURING INTESTINAL DIGESTION AND ABSORPTION .1. PHASE-BEHAVIOR AND AGGREGATION STATES OF MODEL LIPID SYSTEMS PATTERNED AFTER AQUEOUS DUODENAL CONTENTS OF HEALTHY ADULT HUMAN-BEINGS

PHYSICAL-CHEMICAL BEHAVIOR OF DIETARY AND BILIARY LIPIDS DURING INTESTINAL DIGESTION AND ABSORPTION .1. PHASE-BEHAVIOR AND AGGREGATION STATES OF MODEL LIPID SYSTEMS PATTERNED AFTER AQUEOUS DUODENAL CONTENTS OF HEALTHY ADULT HUMAN-BEINGS
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DOI:
10.1021/bi00460a011
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发表时间:
1990-02-27
期刊:
影响因子:
2.9
通讯作者:
CAREY, MC
CAREY, MC
中科院分区:
生物学3区
文献类型:
--
作者:
STAGGERS, JE;HERNELL, O;CAREY, MC

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我们开发了平衡相图对应的水脂质组成的上小肠内容物在脂质消化和吸收的成年人。三元脂质体系由胆盐(BS)、混合肠脂质(MIL)(主要是部分离子化脂肪(油酸)酸(FA)和外消旋单油基甘油(MG))和胆固醇(Ch)组成,均在固定的水电解质浓度、pH、温度和压力下进行。典型生理条件(1g/dL总脂质,FA:MG摩尔比为5:1,pH 6.5,0.15M Na+,37 ℃)的凝聚相图。C)与稀释模型胆汁[BS/卵磷脂(PL)/Ch]系统[Carey,M. C.的方法,和Small,D. M.(1978)J. Clin. Invest. 61,998-1026]。我们确定了两个单相区组成的混合胶束和层状液晶,分别和两相区,一个由Ch一水合物晶体和Ch饱和胶束和其他生理相关的Ch和MIL饱和的混合胶束和单层囊泡组成。一个单一的大三相区的系统中的CH-饱和胶束,CH一水合物晶体,和液晶。通过增加总脂质浓度(0.25-5 g/dL)、pH值(5.5-7.5)和FA:MG摩尔比(5-20:1),扩大了在其他典型生理条件下的胶束相边界,导致生理两相区的尺寸减小。通过准弹性光散射(QLS)测量的平均颗粒流体动力学半径(hivinRh)表明从胶束(< 40埃)到胶束(< 40埃)的突然增加。至胶束加囊泡尺寸(400-700埃)进入这个两相区的时候随着相对脂质组成在这个区域内,单层囊泡自发形成共沉淀后,其大小随时间的函数显着变化,仅在4天后达到平衡值。此外,囊泡、hivin、Rh值受MIL:混合胆汁盐(MBS)比、pH、总脂质浓度和FA:MG比的影响,但不受Ch含量的影响。相比之下,胶束系统平衡迅速,和他们的.hivin.Rh值只有轻微的生理重要性的物理化学变量的影响。与BS-PL-Ch系统[Mazer,N.一、Carey,M. C.(1983)Biochemistry 22,426-442],当接近胶束相边界时,没有发生胶束尺寸的分歧。在模拟的“肠”pH值(5.5-7.5)在胶束和生理两相区的FA的电离状态主要是1:1的二油酸氢钠,一种不溶性的溶胀“酸皂”化合物。通过相分离和分析,两相区各组成相的连线表明混合胶束被MIL和Ch饱和,共存囊泡被MBS饱和,这些观察结果为理解成年人在脂质消化和吸收过程中肠上皮含水内容物的物理化学状态提供了一个基本框架[见Hernell等人(1990年)(配套文件)]。
We developed equilibrium phase diagrams corresponding to aqueous lipid compositions of upper small intestinal contents during lipid digestion and absorption in adult human beings. Ternary lipid system were composed of a physiological mixture of bile salts (BS),1 mixed intestinal lipids (MIL), principally partially ionized fatty (oleic) acid (FA) plus racemic monooleylglycerol (MG), and cholesterol (Ch), all at fixed aqueous-electrolyte concentrations, pH, temperature, and pressure. The condensed phase diagram for typical physiological conditions (1 g/dL total lipids, FA:MG molar ration of 5:1, pH 6.5, 0.15 M Na+ at 37.degree. C) was similar to that of a dilute model bile [BS/lecithin (PL)/Ch] system [Carey, M. C., and Small, D. M. (1978) J. Clin. Invest. 61, 998-1026]. We identified two one-phase zones composed of mixed micelles and lamellar liquid crystals, respectively, and two-phase zones, one composed of Ch monohydrate crystals and Ch-saturated micelles and the other of physiologic relevance composed of Ch- and MIL-saturated mixed micelles and unilamellar vesicles. A single large three-phase zone in the system was composed of Ch-saturated micelles, Ch monohydrate crystals, and liquid crystals. Micellar phase boundaries for otherwise typical physiological conditions were expanded by increases in total lipid concentration (0.25-5 g/dL), pH (5.5-7.5), and FA:MG molar ratio (5-20:1), resulting in a reduction of the size of the physiological two-phase zone. Mean particle hydrodynamic radii (.hivin.Rh), measured by quasielastic light scattering (QLS), demonstrated an abrupt increase from micellar (< 40 .ANG.) to micelle plus vesicle sizes (400-700 .ANG.) as this two-phase zone was entered. With relative lipid composition within this zone, unilamellar vesicles formed spontaneously following coprecipitation, and their sizes changed markedly as functions of time, reaching equilibrium values only after 4 days. Further, vesicle .hivin.Rh values were influenced appreciably by MIL:mixed bile salt (MBS) ratio, pH, total lipid concentration, and FA:MG ratio, but not by Ch content. In comparison, micellar systems equilibrated rapidly, and their .hivin.Rh values were only slightly influenced by physical-chemical variables of physiological importance. In contrast to the BS-PL-Ch system [Mazer, N. A., and Carey, M. C. (1983) Biochemistry 22, 426-442], no divergence in micellar sizes occurred as the micellar phase boundary was approached. The ionization state of FA at simulated "intestinal" pH values (5.5-7.5) in the micellar and physiologic two-phase zones was principally that of 1:1 sodium hydrogen dioleate, an insoluble swelling "acid soap" compound. By phase separation and analysis, tie-lines for the constituent phases in the two-phase zone demonstrated that the mixed micelles were saturated with MIL and Ch and the coexisting vesicles were saturated with MBS, but not with Ch. These observations provide a fundamental framework for understanding the physical-chemical state of aqueous upper intestinal contents during lipid digestion and absorption in adult human beings [see Hernell et al. (1990) (companion paper)].2.