Lysosome membrane permeability to amines

被引:37
作者
Andrew, CL
Klemm, AR
Lloyd, JB
机构
[1] ALFRED I DUPONT INST,JEFFERSON MED COLL,DIV DEV BIOL,WILMINGTON,DE 19899
[2] ALFRED I DUPONT INST,NEMOURS RES PROGRAM,WILMINGTON,DE 19899
来源
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | 1997年 / 1330卷 / 01期
关键词
lysosome membrane; amine (organic);
D O I
10.1016/S0005-2736(97)00145-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The permeability of rat liver lysosomes to xenobiotic organic compounds possessing nitrogen functions was investigated, using an osmotic-protection methodology. It was first shown that rat liver lysosomes are stable for at least one hour when incubated in 250 mM sucrose within the pH range 5 to 9. Primary and tertiary amines with pK(a) values within this pH range, and with differing numbers of aliphatic hydroxy or ether groups, were chosen for study and their permeability investigated at a range of pH values. The results indicate that uncharged amines can cross the lysosome membrane, and that the permeability of such molecules can be predicted from their total hydrogen-bonding capacity. The notional hydrogen-bonding capacity of an uncharged tri-substituted nitrogen with no attached hydrogen atom, as in pyridine or in a tertiary aliphatic amine, is deduced to be approximately 1, and that of an uncharged primary amine approximately 2. A hydrogen-bonding capacity of at least 11 is deduced for cationic nitrogen, implying that most if not all molecules containing a charged nitrogen atom cannot cross the lysosome membrane by passive diffusion. The implications for lysosome physiology and pharmacology are discussed. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:71 / 82
页数:12
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