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L Swell

Publications and source records attributed to L Swell.

At least 37 records · Page 2Linked to original sources
PubMed1976

Quantitative aspects of the conversion of 5 beta-cholestane intermediates to bile acids in man.

The in vivo conversion of several 5 beta-cholestane intermediates to primary bile acids was investigated in three patients with total biliary diversion. The following compounds were administered intravenously: 5 beta-[G-3H]-cholestane-3 alpha, 7 alpha-diol, 5 beta-[G-3H]cholestane-3 alpha, 7alpha, 26-triol, and 5 beta-[24-14C]cholestane-3 alpha, 7 alpha-25-triol. Bile was then collected quantitatively at frequent intervals for the next 21 to 28 h. The administered 5 beta-[G-3H]cholestane-3alpha, 7alpha, 26-triol was found to be efficiently converted to cholic and chenodeoxycholic acids in two patients; 61 and 75% of the administered label was found in primary bile acids. The proportion of labeled cholic to chenodeoxycholic acid was 1.20 and 1.02 in the bile of these patients, indicating that the C-26 triol was efficiently converted to cholic acid. The ratio of cholic to chenodeoxycholic acid (mass) in the bile of these patients was 1.23 and 2.32. The 5 beta-cholestane-3alpha, 7alpha-diol intermediate was also efficiently converted (71%) to both primary bile acids. The cholic to chenodeoxycholic acid ratios by mass and label were similar (2.97 versus 2.23). By contrast, the 5beta-cholestane-3alpha, 7alpha, 25-triol was poorly converted to bile acids in three patients. Following the administration of this compound almost all of the administered radioactivity found in the bile acid fraction was in cholic acid (5 to 19%) and very little (less than 5%) was found in chenodeoxycholic acid. These findings indicate that ring hydroxylation at position 12 is not materially hindered by the presence of a hydroxyl group on the side chain at C-26 in patients with biliary diversion. The labeled C-26-triol which was efficiently converted to both primary bile acids in a proportion similar to that which was observed for the bile acids synthesized by the liver suggests that this 5beta-cholestane derivative may be a major intermediate in the synthesis of both cholic and chenodeoxycholic acids.

Bile Acids and Salts↗
PubMed1975

Mechanism of secretion of biliary lipids. I. Role of bile canalicular and microsomal membranes in the synthesis and transport of biliary lecithin and cholesterol.

The role of bile canalicular and microsomal membranes in the synthesis and transport of biliary lipids was investigated by using the isolated perfused rat liver model. Labeled lecithin precursors ((3H)-palmitic acid, (14C)linoleic acid, (3H)choline, and 32PO4) and a cholesterol precursor ((3H)mevalonic acid) were administered with and without sodium taurocholate. The incorporation pattern of these labeled precursors into linoleyl and arachidonyl lecithins and cholesterol fractions of microsomes, bile canaliculi, and bile were examined at 30-min intervals up to 90 min. Marker enzymes and electron microscopy indicated that isolated subfractions of plasma membranes were enriched with bile canaliculi (less than 10 percent microsomal contamination). Taurocholate significantly stimulated the incorporation of 32PO4, (3H)choline, (3H)palmitic acid, and (14C)linoleic acid into linoleyl and arachidonyl lecithin with parallel incorporation curves for microsomal and bile canalicular membranes throughout the 90-min study period. During the 30-60-min period, however, these same lecithin fractions in bile significantly exceeded the specific activity of the membrane lecithins. The enzyme CDP-choline diglyceride transferase was virtually absent from canaliculi relative to microsomes, indicating that canaliculi lack the capacity for de novo lecithin synthesis. Incorporation of (3H)mevalonic acid into membranous and biliary cholesterol followed a pattern similar to that for lecithin. These data provide evidence that (a) biliary lecithin and cholesterol are derived from a microsomal subpool regulated by the flux of enterohepatic bile acids, (b) the role of the bile canalicular membranes with respect to biliary lipids is primarily transport rather than synthesis, and (c) lecithin and cholesterol are transported together from microsomes to bile. The findings are consistent with the existence of a cytoplasmic lipid complex within the hepatocyte which is actively involved in the intermembrane transport of biliary lipid.

Animals↗
PubMed1975

Bile acid metabolism in cirrhosis. IV. Characterization of the abnormality in deoxycholic acid metabolism.

Several recent studies have demonstrated that patients with cirrhosis frequently lack deoxycholic acid in bile and plasma. In order to explain this observation, comparative experiments on the colonic absorption of deoxycholic acid and on the colonic conversion of cholic to deoxycholic acid were carried out in the cirrhotic patients with normal and very low percentages of deoxycholic acid. Deoxycholic or cholic acid (100 mg) plus 5 muc of each [14C] bile acid were administered by enema to 8 patients with and 5 without liver disease. Deoxycholic acid produced a significant increase in the percentage of biliary deoxycholic acid in patients with cirrhosis. However, the rate of appearance of 14C-deoxycholic acid in patients with cirrhosis was slower than in normal control subjects. Distribution of the 14C activity among the bile acids indicated that rehydroxylation of deoxycholic to cholic acid did not occur. The distribution of 14C activity in biliary bile acids after the rectal administration of [14C]cholic acid showed that patients with severe cirrhosis converted [14C]cholic to [14C]deoxycholic acid at a much slower rate than did cirrhotic patients with normal percentages of biliary deoxycholic acid. Feeding of cholic acid (450 mg per day) for 3 days to 4 cirrhotic patients resulted in a 2-fold increase in the percentage of biliary cholic acid, but only a small increase in the percentage of deoxycholic acid. In a separate group of 9 cirrhotic patients, fecal bile acid analysis indicated that cirrhotic patients had a significantly lower percentage of deoxycholic acid than 12 patients without liver disease; there was no significant difference in fecal lithocholic acid. The data suggest that alteration of bacterial flora and/or altered conditions for bacterial 7alpha-dehydroxylase enzyme activity in the colon could account for the virtual absence of biliary deoxycholic acid in severely cirrhotic patients.

Adult↗
PubMed1975

Evidence for the existence of definitive hepatic cholesterol precursor compartments for bile acids and biliary cholesterol in man.

A bile fistula patient was administered intravenously a constant infusion of [3H]mevalonic acid for 4 hrs, and then after 2 weeks he was given a pulse of [3H]mevalonic acid. Bile and blood were collected at frequent intervals. The specific activity-time course curves did not show a precursor-product relationship between biliary cholesterol, plasma free cholesterol and bile acids. Both the constant infusion and pulse labeling data indicated that the bile acid precursor had a more rapid rate of turnover than plasma or biliary cholesterol; the biliary cholesterol precursor turned over more rapidly than plasma cholesterol. The data suggest the presence of multiple hepatic cholesterol precursor compartments. Bile acids may be derived predominantly from newly synthesized cholesterol in man.

Bile Acids and Salts↗
PubMed1973

Cholic acid synthesis as an index of the severity of liver disease in man.

Bile acid pool size and kinetics were determined in 17 patients with cirrhosis and 11 patients without liver disease and correlated with the severity of liver disease as determined by the usual clinical and laboratory criteria. In order to assess the severity of liver disease, a grading system was devised which assigned numerical values to various clinical signs and laboratory results. The total clinical score and the patients were divided into two groups of advanced (7-18 points) or mild (1-6 points) cirrhosis. The clinical rating was then correlated with the various aspects of bile acid metabolism. Cholic acid synthesis was markedly reduced in the early stages of cirrhosis and continued to decrease with the advancement of the liver disease. There was an inverse correlation between synthesis of cholic acid and the severity of cirrhosis. Nine of the 10 patients with advanced cirrhosis and a very low cholic acid synthetic rate (average 68 mg per day) died within one to 13 months from the start of the study. Patients with mild cirrhosis also had significantly reduced cholic acid synthesis (average 152 mg per day) but they all were well and alive three to 23 months after the study. In contrast, chenodeoxycholic acid synthesis was not markedly affected in either patients with mild or advanced cirrhosis. There was also a high degree of correlation between the fractional daily turnover rate of cholic acid and the severity of liver disease. The fractional daily turnover rate of cholic acid was greatly reduced (50%) in patients with advanced cirrhosis. Deoxycholic acid was reduced in patients with mild cirrhosis and virtually absent from the bile of patients with advanced cirrhosis. The findings of the present report provide evidence that cholic acid synthesis is a sensitive indicator of the hepatocellular damage, whereas chenodeoxycholic acid synthesis is relatively unaffected by cirrhosis. The selective alteration in cholic acid synthesis probably resides in a deficiency of one or more enzymes regulating the formation of the 3-keto, 7 alpha, 12 alpha-dihydroxy precursor of cholic acid.

Adult↗