Effects of side chain length on ionization behavior and transbilayer transport of unconjugated dihydroxy bile acids: a comparison of nor-chenodeoxycholic acid and chenodeoxycholic acid.

Abstract:

:13C-NMR spectroscopy was used to examine the effect of side chain length on the ionization properties and transmembrane transport rate of 3 alpha,7 alpha-dihydroxy bile acids. When solubilized in taurocholate micelles, [23-13C]nor-chenodeoxycholic acid (nor-CDCA) had a pKa of 6.1, similar to that of CDCA (pKa 6.2), its C24 homologue. In unilamellar phosphatidylcholine vesicles, the pKa of nor-CDCA was 7.0, whereas that of CDCA was 6.6. Lineshape analysis indicated that the rate of ionization of nor-CDCA as a micellar solute or as a vesicle component was very slow (0.4 x 10(5) sec-1) compared to that of acetic acid in water (8.7 x 10(5) sec-1). Lineshape analysis of spectra of the protonated form of nor-CDCA at acidic bulk pH indicated that the transbilayer transport rate of nor-CDCA (580 sec-1) was six times faster than that of CDCA (100 sec-1). It is proposed that the shorter side chain of the nor-CDCA molecule causes it to reside more deeply inside the vesicle bilayer than CDCA, explaining its weaker ionization and more rapid flip-flop rate. These in vitro experiments imply that, in vivo, a given C23 nor-dihydroxy bile acid will ionize less readily when present in membranes, and it will also flip-flop faster than its C24 homologue.

journal_name

J Lipid Res

authors

Ko J,Hamilton JA,Ton-Nu HT,Schteingart CD,Hofmann AF,Small DM

subject

Has Abstract

pub_date

1994-05-01 00:00:00

pages

883-92

issue

5

eissn

0022-2275

issn

1539-7262

journal_volume

35

pub_type

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