Lysosome membrane permeability to amines

• Published in: Biochimica et biophysica acta 1997-11, Vol.1330 (1), p.71-82
• Main Authors: Andrew, Carole L, Klemm, Ann R, Lloyd, John B
• Format: Article
• Language: English
• Subjects: Acetylglucosaminidase - metabolism; Amine (organic); Amines - metabolism; Animals; Cell Membrane Permeability; Hydrogen-Ion Concentration; Liver - enzymology; Liver - metabolism; Lysosome membrane; Lysosomes - enzymology; Lysosomes - metabolism; Rats
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/S0005-2736(97)00145-4

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 p K 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.