LYSOSOME MEMBRANE-PERMEABILITY TO AMINES

The permeability of rat liver lysosomes to xenobiotic organic compound s possessing nitrogen functions was investigated, using an osmotic-pro tection methodology. It was first shown that rat liver lysosomes are s table for at least one hour when incubated in 250 mM sucrose within th e pH range 5 to 9. Primary and tertiary amines with pK(a) values withi n this pH range, and with differing numbers of aliphatic hydroxy or et her groups, were chosen for study and their permeability investigated at a range of pH values. The results indicate that uncharged amines ca n cross the lysosome membrane, and that the permeability of such molec ules can be predicted from their total hydrogen-bonding capacity. The notional hydrogen-bonding capacity of an uncharged tri-substituted nit rogen with no attached hydrogen atom, as in pyridine or in a tertiary aliphatic amine, is deduced to be approximately 1, and that of an unch arged 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 lyso some membrane by passive diffusion. The implications for lysosome phys iology and pharmacology are discussed. (C) 1997 Elsevier Science B.V.