Lysosome membrane permeability to amines.
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 pKa 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.
Andrew
C L
CL
Division of Developmental Biology, Jefferson Medical College, Alfred I. duPont Institute, Wilmington, DE 19899, USA.
Klemm
A R
AR
Lloyd
J B
JB
D000118:Acetylglucosaminidase / Q000378:metabolism; D000588:Amines / Q000378:metabolism*; D000818:Animals; D002463:Cell Membrane Permeability; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism*; D051381:Rats
D000588:Amines; D000118:Acetylglucosaminidase