scholarly journals Differential hepatic processing and biliary secretion of head-group and acyl chains of liposomal phosphatidylcholines

1991 ◽  
Vol 275 (1) ◽  
pp. 139-144 ◽  
Author(s):  
H J Verkade ◽  
J T Derksen ◽  
A Gerding ◽  
G L Scherphof ◽  
R J Vonk ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Degradation Products ◽  
Acyl Chain ◽  
Quantitative Difference ◽  
Biliary Secretion ◽  
Synthesis Rate ◽  
Head Group ◽  
Bile Drainage ◽  
Acyl Chains

To investigate the contribution of plasma-derived phosphatidylcholine (PC) to bile PC, the hepatic processing and biliary secretion of liposome-associated PC was studied in rats. For this purpose, small unilamellar vesicles (SUV), containing trace amounts of [2-palmitoyl-9,10-3H]dipalmitoylphosphatidylcholine ([palmitoyl-3H]DPPC), [choline-14C]-dipalmitoylphosphatidylcholine ([choline-14C]DPPC), di[14C]palmitoylphosphatidylcholine ([14C]DPPC) or di[1-14C]-oleoylphosphatidylcholine ([14C]DOPC), were administered intravenously to unanaesthetized rats, equipped with permanent catheters in heart and bile duct. Biliary secretion of the 14C-head-group label of DPPC was very slow (0.3% of injected dose in 4 h), whereas the [3H]palmitoyl label was secreted at a much higher rate (16% in 4 h), but only after substantial catabolism of the acyl chain. To study the latter process in more detail, we compared hepatic metabolism and biliary secretion of [1-14C]acyl-labelled DPPC and DOPC. In rats with an 8-day bile drainage, degradation products of the oleoyl chain were utilized for synthesis of bile acids, which were subsequently secreted into the bile (2% in 6 h). A much smaller fraction (0.6% in 6 h) was secreted as PC and lyso-PC. When bile drainage was started immediately after SUV injection, i.e. a situation with a low hepatic bile acid synthesis rate and a high phospholipid secretion, the secretion of [14C]DOPC-derived radioactivity in the form of bile acids was decreased (0.2% in 6 h), and that as (lyso-)PC increased (1.5% in 6 h). Biliary secretion of DPPC palmitoyl chains in bile-diverted rats was much less than that of the oleoyl chains, and occurred predominantly as PC and lyso-PC (0.6%, compared with 0.4% as bile acids in 6 h). Breath analyses demonstrated that a considerable fraction of both acyl chains was oxidized to CO2 and expired: 25.1% of the administered label for oleoyl chains and 13.4% for palmitoyl chains respectively in a 4 h period. The results of this study indicate that liposomal PC is only minimally secreted into bile via a direct pathway; the bulk is extensively degraded in the liver. Resulting products are partly secreted into bile, as bile acid or as resynthesized PC. There appears to be a quantitative difference in the metabolism of oleoyl and palmitoyl acyl chains.

Interactions of the Antimicrobial Peptide Maculatin 1.1 and Analogues with Phospholipid Bilayers

2011 ◽  
Vol 64 (6) ◽  
pp. 798 ◽  
Author(s):  
David I. Fernandez ◽  
Marc-Antoine Sani ◽  
Frances Separovic
Keyword(s):  
Antimicrobial Peptide ◽  
Solid State Nmr ◽  
Acyl Chain ◽  
Head Group ◽  
Group Interactions ◽  
Bacterial Membranes ◽  
Helical Content ◽  
Lipid System ◽  
Acyl Chains ◽  
Mixed Bilayer

The interactions of the antimicrobial peptide, maculatin 1.1 (GLFGVLAKVAAHVVPAIAEHF-NH2) and two analogues, with model phospholipid membranes have been studied using solid-state NMR and circular dichroism spectroscopy. Maculatin 1.1 and the P15G and P15A analogues displayed minimal secondary structure in water, but with zwitterionic dimyristoylphosphatidylcholine (DMPC) vesicles displayed a significant increase in α-helical content. In mixed phospholipid vesicles of DMPC and anionic dimyristoylphosphatidylglycerol (DMPG), each peptide was highly structured with ~80% α-helical content. In DMPC vesicles, the native peptide displayed moderate head group interaction and significant perturbation of the lipid acyl chains. In DMPC/DMPG vesicles, maculatin 1.1 promoted formation of a DMPG-enriched phase and moderately increased disorder towards acyl chain ends of DMPC in the mixed bilayer. Both analogues showed reduced phospholipid head group interactions with DMPC but displayed significant interactions with the mixed lipid system. These effects support the preferential activity of these antimicrobial peptides for bacterial membranes.

scholarly journals Effect of ursodeoxycholic acid on lipid metabolism: through the prism of evidence from 2019.

2020 ◽  
Vol 46 (1) ◽  
pp. 83-88
Author(s):  
N. B. Gubergrits ◽  
N.V. Byelyayeva ◽  
T. L. Mozhyna ◽  
G. M. Lukashevich ◽  
P. G. Fomenko
Keyword(s):  
Lipid Metabolism ◽  
Bile Acid ◽  
Bile Acids ◽  
De Novo ◽  
Gallstone Disease ◽  
Farnesoid X Receptor ◽  
Synthesis Rate ◽  
Primary Biliary Cholangitis ◽  
Fractional Synthesis Rate ◽  
Fractional Synthesis

After the discovery of the method of ursodeoxycholic acid’s (UDCA) synthesis and the publication of evidence confirming its ability to reduce the lithogenic properties of bile, active clinical use of UDCA began in the world. This drug, which has pleiotropic effect (choleretic, cytoprotective, immunomodulatory, antiapoptic, litholytic, hypocholesterolemic), has proven its effectiveness in the treatment various diseases: primary biliary cholangitis, intrahepatic cholestasis of pregnancy, gallstone disease. Being a tertiary bile acid, UDCA stimulates bile acid synthesis by reducing the circulating fibroblast growth factor 19 and inhibiting the activation of the farnesoid X-receptor (FXR), which leads to the induction of cholesterol-7α-hydroxylase, a key enzyme in the synthesis of bile acid de novo, mediating the conversion of cholesterol into bile acids. Changes in the formation of bile acids and cholesterol while taking UDCA intake is accompanied by activation of the main enzyme of cholesterol synthesis - 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Under the influence of UDCA the activity of stearoyl-Coa desaturase (SCD) in visceral white adipose tissue increases. According to studies conducted in 2019, UDCA improves lipid metabolism by regulating the activity of the ACT/mTOR signaling pathway, reduces the synthesis of cholesterol, decreases the fractional synthesis rate of cholesterol and the fractional synthesis rate of triglycerides. It has been proved that UDCA is accompanied by a decrease in the level of total cholesterol and low density lipoprotein cholesterol.

scholarly journals The role of conjugation reactions in enhancing biliary secretion of bile acids

1983 ◽  
Vol 214 (3) ◽  
pp. 923-927 ◽  
Author(s):  
D A Vessey ◽  
J Whitney ◽  
J L Gollan
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Hepatic Uptake ◽  
Biliary Secretion ◽  
Side Chain ◽  
Isolated Perfused Rat Liver ◽  
Rat Livers ◽  
Kinetics Of ◽  
Methylene Group

Shortening the five-carbon carboxylic acid side chain of cholic acid by one methylene group gave rise to a bile acid (norcholate) that was not a substrate for the bile acid-conjugating enzymes. The metabolism and biliary secretion of norcholate in intact liver was examined in the isolated perfused rat liver system. When rat livers were perfused with 14-20 microM solutions of norcholate for 10 min, norcholate was found in the unconjugated form in liver, venous effluent and bile. Neither tauronorcholate nor glyconorcholate was detectable by high-pressure liquid chromatography or fast-atom-bombardment mass spectrometry. The kinetics of hepatic uptake and biliary secretion of norcholate was compared with that for cholate, taurocholate and chemically synthesized tauronorcholate. The latter three bile acids were completely cleared from the perfusate and efficiently secreted into the bile. However, norcholate was incompletely extracted from the perfusate, and this was shown to be at least partially due to its relatively lower rate of hepatic uptake. Furthermore, the rate of norcholate secretion into bile was greatly reduced relative to the secretion of cholate or chemically synthesized tauronorcholate, even though the concentration of norcholate in the liver was comparatively high. These data demonstrate that the conjugation of bile acids greatly facilitates their secretion into bile.

Influence of side-chain charge on hepatic transport of bile acids and bile acid analogues

1985 ◽  
Vol 249 (4) ◽  
pp. G479-G488 ◽  
Author(s):  
M. S. Anwer ◽  
E. R. O'Maille ◽  
A. F. Hofmann ◽  
R. A. DiPietro ◽  
E. Michelotti
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Liver Cell ◽  
Hepatic Uptake ◽  
Biliary Secretion ◽  
Side Chain ◽  
Bile Fistula ◽  
Bile Acid Derivatives ◽  
Derivatives Of ◽  
Secretion Rates

The importance of side-chain charge on hepatic uptake and biliary secretion of bile acids and analogues was studied using the isolated, perfused rat liver and the anesthetized rat with a bile fistula. Derivatives of cholic acid with negative, neutral, zwitterionic, or positive charges on the side chain were synthesized and studied. Hepatic uptake by the isolated perfused liver, determined by measuring the rate of disappearance of a single 20-mumol bolus added to the perfusate, was strongly influenced by side-chain charge. A fully positively charged bile acid derivative (cholylcholamine) and two fully zwitterionic bile acid derivatives (CHAPS and cholyllysine) showed no appreciable uptake (less than 1% of the uptake rate of cholyltaurine). Bile acid derivatives existing mostly in cationic form (cholylamine) at pH 7.4, in neutral form (cholylglycylhistamine), or in divalent anion form (cholylaspartate and cholylcysteate) had an uptake rate that was greater but only 7-19% that of cholyltaurine. Side-chain charge also appeared to influence the rate of secretion into bile. Bile acids existing in mono- or dianionic form were well secreted (greater than 95% of dose in 2 h) into the bile, but all other derivatives had much lower secretion rates (less than 20% of dose in 2 h). When the biliary secretion of each bile acid derivative was expressed in relation to the amount that had entered the liver, relative secretion rates (presumably from liver cell) into bile decreased in the following order: cholyltaurine greater than cholylaspartate and cholylcysteate greater than CHAPS greater than cholyllysine greater than cholylglycylhistamine approximately equal to cholylamine. In bile fistula rats, cholylaspartate was quantitatively secreted into bile when infused at rates below its secretory maximum, whereas only very low biliary secretion rates of CHAPS were observed even during relatively high infusion rates; cholylamine was cholestatic. The above data show that, although uncharged and anionic derivatives of cholic acid may be taken up by the liver at a moderate rate, only anionic derivatives (both monovalent and divalent) are well secreted from within the liver cell into bile. A single negative charge on the side chain appears to be required for optimal transport of a bile acid from sinusoidal blood to bile.

The Biliary Excretion of Sulphated and Non-Sulphated Bile Acids and Bilirubin in Patients with External Bile Drainage

1984 ◽  
Vol 67 (1) ◽  
pp. 61-68 ◽  
Author(s):  
James S. Dooley ◽  
Carl Bartholomew ◽  
John A. Summerfield ◽  
Barbara H. Billing
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Biliary Excretion ◽  
Total Bilirubin ◽  
Serum Bilirubin ◽  
Bilirubin Concentration ◽  
Biliary Decompression ◽  
Bilirubin Excretion ◽  
Bile Drainage ◽  
The Difference

1. The biliary excretion of total bilirubin and bile acids, and the fate of tracer doses of radioactive sulphated and non-sulphated bile acids, were studied in patients with percutaneous transhepatic bile drainage. 2. Non-sulphated bile acids were excreted in bile early after biliary decompression, and the serum total 3α-hydroxy bile acid concentrations fell rapidly to normal. Biliary bilirubin excretion was both less than and delayed compared with that of bile acids, and the serum bilirubin concentration fell more slowly. 3. The serum disappearance of [3H]chenodeoxycholate-3-sulphate was slower than that of [14C]glycocholate in all patients with bile drainage, the difference being more marked in the jaundiced patients. 4. The radioactive sulphated bile acids were recovered predominantly in the urine of the jaundiced patients. In contrast [14C]glycocholate was excreted almost exclusively in bile. In an anicteric patient, radioactive sulphated bile acid disappeared from the serum more quickly, and biliary recovery exceeded that in the urine. 5. The studies demonstrate the differences in handling of total bilirubin, and sulphated and non-sulphated bile acids in man after the relief of bile duct obstruction. The biliary excretion of radioactive labelled sulphated bile acids is low for at least 1 week after biliary drainage, but later becomes the predominant route for excretion in the anicteric patient.

scholarly journals Acyl Chain Specificity of Marine Streptomyces klenkii PhosPholipase D and Its Application in Enzymatic Preparation of Phosphatidylserine

2021 ◽  
Vol 22 (19) ◽  
pp. 10580
Author(s):  
Rongkang Hu ◽  
Ruiguo Cui ◽  
Dongming Lan ◽  
Fanghua Wang ◽  
Yonghua Wang
Keyword(s):  
Phospholipase D ◽  
Substrate Binding ◽  
Acyl Chain ◽  
Catalytic Efficiency ◽  
Head Group ◽  
Acyl Chain Length ◽  
Hydrogen Bond Interactions ◽  
Binding Pockets ◽  
Acyl Chains ◽  
Marine Streptomyces

Mining of phospholipase D (PLD) with altered acyl group recognition except its head group specificity is also useful in terms of specific acyl size phospholipid production and as diagnostic reagents for quantifying specific phospholipid species. Microbial PLDs from Actinomycetes, especially Streptomyces, best fit this process requirements. In the present studies, a new PLD from marine Streptomyces klenkii (SkPLD) was purified and biochemically characterized. The optimal reaction temperature and pH of SkPLD were determined to be 60 °C and 8.0, respectively. Kinetic analysis showed that SkPLD had the relatively high catalytic efficiency toward phosphatidylcholines (PCs) with medium acyl chain length, especially 12:0/12:0-PC (67.13 S−1 mM−1), but lower catalytic efficiency toward PCs with long acyl chain (>16 fatty acids). Molecular docking results indicated that the different catalytic efficiency was related to the increased steric hindrance of long acyl-chains in the substrate-binding pockets and differences in hydrogen-bond interactions between the acyl chains and substrate-binding pockets. The enzyme displayed suitable transphosphatidylation activity and the reaction process showed 26.18% yield with L-serine and soybean PC as substrates. Present study not only enriched the PLD enzyme library but also provide guidance for the further mining of PLDs with special phospholipids recognition properties.

scholarly journals Hepatic overexpression of Abcb11 in mice promotes the conservation of bile acids within the enterohepatic circulation

2013 ◽  
Vol 304 (2) ◽  
pp. G221-G226 ◽  
Author(s):  
Anne S. Henkel ◽  
Karin E. R. Gooijert ◽  
Rick Havinga ◽  
Renze Boverhof ◽  
Richard M. Green ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Enterohepatic Circulation ◽  
Transport Protein ◽  
Synthesis Rate ◽  
Hepatic Expression ◽  
Stable Isotope Dilution ◽  
Gene And Protein Expression ◽  
The Impact ◽  
Total Bile Acids

The bile salt export pump, encoded by ABCB11, is the predominant canalicular transport protein for biliary bile acid secretion. The level of ABCB11 expression in humans is widely variable yet the impact of this variability on human disease is not well defined. We aim to determine the effect of hepatic Abcb11 overexpression on the enterohepatic circulation (EHC) in mice. We used a stable isotope dilution technique in transgenic mice overexpressing hepatic Abcb11 (TTR- Abcb11) to determine the pool size, fractional turnover rate (FTR), and synthesis rate of the primary bile acid, cholic acid (CA). The gallbladder was cannulated to determine bile flow, bile acid composition, and the biliary secretion rates of CA, total bile acids, phospholipid, and cholesterol. The combined data allowed for estimation of the CA cycling time and the fraction of CA lost per cycle. Hepatic and intestinal gene and protein expression were determined by qPCR and Western blot. Abcb11 overexpression strongly decreased FTR and synthesis rate of CA. Abcb11 overexpression decreased the fraction of CA that was lost per cycle of the EHC. Hepatic expression of Cyp7a1 was suppressed by nearly 50% and ileal expression of FGF15 was increased more than eightfold in TTR- Abcb11 mice. Despite the increased intestinal reabsorption of bile acids, ileal Asbt expression was suppressed. Hepatic Abcb11 overexpression in mice increases the conservation of bile acids within the enterohepatic circulation. These data provide strong evidence for the existence of feed-forward communication between hepatic expression of a bile acid transport protein and the intestine.

Determination of the Pool Size and Synthesis Rate of Bile Acids by Measurements in Blood of Patients with Liver Disease

1980 ◽  
Vol 58 (6) ◽  
pp. 485-492 ◽  
Author(s):  
L. R. Engelking ◽  
S. Barnes ◽  
B. I. Hirschowitz ◽  
C. A. Dasher ◽  
J. G. Spenney ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Bile Acids ◽  
Pool Size ◽  
Synthesis Rate ◽  
Bile Acid Pool ◽  
Bile Acid Concentration ◽  
Bile Acid Pool Size ◽  
Permit Application

1. A simplified technique for the measurement of bile-acid pool size and synthesis rate has been developed in patients with liver disease. Isotope dilution studies in blood and bile were performed after intravenous injection of [24–14C]cholic acid with radioimmunoassay for the measurement of the bile-acid concentration. The interpolated pool sizes and synthesis rates, determined from results from both blood and bile, were not significantly different The concentration of bile acids in the blood of healthy controls was not sufficiently elevated to permit application of this technique. 2. Three out of six patients with cirrhosis had a markedly reduced pool size compared with that of controls, whereas those with cholestasis had an unchanged pool size. The daily synthesis rate was reduced in both groups. Liver disease caused a redistribution

Mechanism of bile acid-induced biliary lipid secretion in the rat: effect of conjugated bilirubin

1993 ◽  
Vol 264 (3) ◽  
pp. G462-G469 ◽  
Author(s):  
H. J. Verkade ◽  
R. Havinga ◽  
A. Gerding ◽  
R. J. Vonk ◽  
F. Kuipers
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Genetic Defect ◽  
Specific Interaction ◽  
Biliary Secretion ◽  
Biliary Lipid ◽  
Bile Acid Concentration ◽  
Lipid Secretion ◽  
Cholesterol Secretion ◽  
Conjugated Bilirubin

We have compared the effects of bilirubin and bilirubin ditaurate (BDT) on biliary phospholipid and cholesterol secretion in unanesthetized normal Wistar (NW) and Groningen Yellow (GY) Wistar rats under various experimental conditions. GY rats express a genetic defect in biliary secretion, but not in hepatic uptake, of various organic anions. Under physiological conditions, NW and GY rats showed similar biliary secretion rates of bile acids and of bilirubin, despite the fact that bilirubin concentrations in GY plasma were 25 times as high and in GY livers three times as high as in NW plasma and livers, respectively. Secretion of cholesterol and phospholipids was not impaired in GY rats under these conditions. Biliary secretion of intravenously injected BDT (3 mumol/100 g body wt) was delayed in eight-day bile-diverted GY rats and showed lower peak values when compared with NW rats. The inhibitory effects of BDT on phospholipid and cholesterol secretion paralleled these differences, being delayed and much less pronounced in GY rats. No overshoot in phospholipid or cholesterol secretion was observed when bilirubin output returned to preinjection values. Stimulation of [14C]choline-labeled phospholipid secretion after a bolus injection of taurochenodeoxycholic acid (1 mumol/100 g body wt) closely followed biliary bile acid concentration. Similarly, inhibition of labeled phospholipid secretion by BDT closely paralleled the biliary bilirubin concentration. Gel filtration studies (Sepharose 4B-CL) under micelle-preserving conditions demonstrated a specific interaction of BDT with biliary bile acids. The presented data indicate that conjugated bilirubin does not inhibit biliary lipid secretion via interaction with bile acids inside the hepatocyte.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Ablating L-FABP in SCP-2/SCP-x null mice impairs bile acid metabolism and biliary HDL-cholesterol secretion

2014 ◽  
Vol 307 (11) ◽  
pp. G1130-G1143 ◽  
Author(s):  
Gregory G. Martin ◽  
Barbara P. Atshaves ◽  
Kerstin K. Landrock ◽  
Danilo Landrock ◽  
Stephen M. Storey ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Physiological Role ◽  
Hdl Cholesterol ◽  
Hepatic Uptake ◽  
Biliary Secretion ◽  
Bile Acid Metabolism ◽  
Fatty Acid Binding ◽  
Bile Acid Concentration ◽  
Biliary Bile Acid

On the basis of their abilities to bind bile acids and/or cholesterol, the physiological role(s) of liver fatty acid-binding protein (L-FABP) and sterol carrier protein (SCP) 2/SCP-x (SCP-2/SCP-x) gene products in biliary bile acid and cholesterol formation was examined in gene-ablated male mice. L-FABP (LKO) or L-FABP/SCP-2/SCP-x [triple-knockout (TKO)] ablation markedly decreased hepatic bile acid concentration, while SCP-2/SCP-x [double-knockout (DKO)] ablation alone had no effect. In contrast, LKO increased biliary bile acid, while DKO and TKO had no effect on biliary bile acid levels. LKO and DKO also altered biliary bile acid composition to increase bile acid hydrophobicity. Furthermore, LKO and TKO decreased hepatic uptake and biliary secretion of high-density lipoprotein (HDL)-derived 22-( N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol), while DKO alone had no effect. Finally, LKO and, to a lesser extent, DKO decreased most indexes contributing to cholesterol solubility in biliary bile. These results suggest different, but complementary, roles for L-FABP and SCP-2/SCP-x in biliary bile acid and cholesterol formation. L-FABP appears to function more in hepatic retention of bile acids as well as hepatic uptake and biliary secretion of HDL-cholesterol. Conversely, SCP-2/SCP-x may function more in formation and biliary secretion of bile acid, with less impact on hepatic uptake or biliary secretion of HDL-cholesterol.

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