Relevance of different apolipoprotein content in binding of homocysteine to plasma lipoproteins.

BACKGROUND AND AIMS: In plasma the atherogenic thiol homocysteine (Hcy) circulates either free or bound to proteins (Pb-Hcy). The present study sets out to evaluate the lipoprotein-Hcy (LP-Hcy) binding in vivo and the possible influence of different apolipoprotein content in this binding, being lipoprotein oxidation a possible mechanism of Hcy-induced damage. METHODS AND RESULTS: In 34 healthy subjects we assayed fasting plasma lipoprotein and correspondent apolipoprotein (apo A-I, apo A-II, apo C-II, apo C-III, apo B, apo(a) and apo E content, and Hcy bound to different plasma protein fractions; moreover ten subjects underwent an oral methionine load in order to evaluate possible "dynamic" modifications of Pb-Hcy and LP-Hcy after induction of hyperhomocysteinemia. Pb-Hcy (mean values 9.22 +/- 1.7 mumol/L) represented about 78% of total plasma Hcy (mean values 11.8 +/- 1.8 mumol/L). Pb-Hcy distribution between the different fractions was as follows (mumol/L): VLDL = 0.25 +/- 0.08 (2.7%); LDL = 0.88 +/- 0.22 (9.5%); HDL = 1.40 +/- 0.36 (15.2%); fractions with density greater than 1.21 g/mL (Lipoprotein-Free Protein Fraction, LPDS) = 6.7 +/- 1.2 (72.6%). Hcy/protein ratios (nmol/mg of protein) in each protein fraction were: VLDL = 0.32 +/- 0.19, LDL = 0.43 +/- 0.37, HDL = 0.26 +/- 0.18, LPDS < 0.1, thus suggesting a higher binding capacity for Hcy by VLDL and LDL. These data were confirmed by the higher increase in Hcy content in LDL and VLDL (76 and 90%, respectively vs 36% and 3.1% for HDL and LPDS fractions) after hyperhomocysteinemia. Lp-Hcy binding significantly correlated with the apo B content of VLDL and LDL and Apo A-I content of HDL. CONCLUSIONS: An important fraction of plasma Hcy circulates bound to LP (about 27% of Pb-Hcy); VLDL and LDL show the highest binding capacity for Hcy, probably due to their content in Apo B, a possible high capacity binding site for Hcy.

Different resistance of mammalian red blood cells to hemolysis by bile salts.

To evaluate why hemolysis of red blood cells (RBC) by bile acids varies in different mammalian species, we determined the mean corpuscular volume (MCV), lipid content and the concentrations of the conjugates of deoxycholate and of NaCl inducing 50% hemolysis of RBC from healthy humans, pigs, horses, cows, sheep and jaundiced humans. A volume of 0.05 mL of washed RBC at 1% hematocrit, which has the same lipid content but different phospholipid composition and number of erythrocytes (owing to the variable MCV), was incubated in taurodeoxycholate (TDC) solution (0-5 mM) to determine the TDC concentration inducing 50% hemolysis (TDC50). The TDC50 was highest in RBC of sheep and decreased within the series sheep > pig > cow > horse > healthy human > jaundiced human, which have generally increasing MCV. The osmotic resistance followed an inverse order, with jaundiced human > healthy human > horse > cow > pig > sheep. Although we found no correlation between the TDC50 and phospholipid composition of the erythrocytes tested, the extent of bile salt-induced hemolysis seemed to depend on both the MCV and the number of erythrocytes in the incubation medium.

Composition of ascitic fluid in liver cirrhosis: bile acid and lipid content.

The concentrations of lipids, bile acids and proteins were evaluated in the ascitic fluid and plasma of 23 cirrhotics. Ascitic fluid density was highly correlated with its protein content, represented mostly by low molecular weight proteins. The ratio of plasma to ascitic fluid concentrations of nine examined proteins increased with molecular weight, indicating a selective ultrafiltration of the peritoneal transudate. Low density lipoproteins in ascitic fluid had modified electrophoretic mobility. Total cholesterol had a higher plasma to ascitic fluid ratio than high density lipoprotein cholesterol, whereas bile acids and proteins had similar plasma to ascitic fluid ratios. Indeed, bile acids strongly bind to circulating albumin: consequently ascitic fluid contains more cholic acid (less hydrophobic) than other bile acids. Analysis of both plasma and ascitic fluid composition in cirrhotics provides useful information on processes regulating passage of blood components into the peritoneal cavity.

[Chemico-physical property and bile acid binding capacity of several antacids]. / Proprietà chimico-fisiche e capacità legante gli acidi biliari di alcuni antiacidi.

Liquid alginate (Gaviscon) binds small amount of bile acids. At pH 7 its viscosity (at low shear rate) is higher than that of other antiacids. High viscosity reduces the diffusion rate of bile salts and glucose and this property can play a role in the treatment of gastro-esophageal and duodeno-gastric refluxes.