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C K Harmon

Publications and source records attributed to C K Harmon.

7 recordsLinked to original sources

Lipid metabolism by the gall-bladder. I. The in situ uptake and metabolism of lysophosphatidylcholine.

Accumulation of lysophosphatidylcholine in gall-bladder bile is involved in the pathogenesis of acute cholecystitis. [1-14C]oleoyl- or [1-14C]palmitoyl-lysophosphatidylcholine was thus instilled in the in situ guinea pig gall-bladder and the absorption and metabolism of the lipid were determined. We found that, after 6 h instillation, 53% of the oleoyl derivative was adsorbed by the gall-bladder, whereasee only 37% of the palmitoyl derivative was absorbed. Although some differences in the metabolism of these two lipids were observed, a major portion of the absorbed radioactivity was found in the gall-bladder wall as phosphatidylcholine. To determine the mechanism of phosphatidylcholine formation from lysophosphatidylcholine by the gall-bladder mucosa, we used lysophosphatidylcholine which was labelled in the fatty acid moiety with 14C and in the choline moiety with 3H. Our data suggest that the mechanism of phosphatidylcholine formation from lysophosphatidylcholine involved acylation with an acyl donor other than a second molecule of lysophosphatidylcholine. We hypothesize that this mechanism as well as others described serve to prevent accumulation of lysophosphatidylcholine within the gall-bladder lumen and thus prevent damage to the gall-bladder mucosa.

1-Acylglycerophosphocholine O-Acyltransferase↗

Lipid metabolism by The gall-bladder. II. The in vitro conversion of lysophosphatidylcholine to phosphatidylcholine.

Lysophosphatidylcholine acyltransferase, which catalyzes the acylation of lysophosphatidylcholine with fatty acid coenzyme A to form phosphatidylcholine, was assayed in gall-bladder mucosa. In guinea pig gall-bladder the activity parallels that of the microsomal enzyme, glucose-6-phosphatase with 3--4-fold enrichment of the activity in the microsomes. Studies with saturated and unsaturated substrates demonstrated highest activity when oleoyl coenzyme A and palmitoyl lysophosphatidylcholine were used and the lowest activity when palmitoyl coenzyme A and palmitoyl lysophosphatidylcholine were used. This activity was demonstrated in the dog, rabbit, cat, calf and human gall-bladder mucosa; however, a wide variation in the amount was observed. Lysophospholipase, which catalyzes the hydrolysis of lysophosphatidylcholine to glycerophosphorylcholine and fatty acid, was also demonstrated in gall-bladder mucosa.

1-Acylglycerophosphocholine O-Acyltransferase↗

Comparison of linoleic acid and stearic acid absorption by the gallbladder.

The absorption of [14C]linoleic acid and [14C]stearic acid in guinea pig bile by the in situ guinea pig gallbladder was compared. Linoleic acid was adsorbed at a faster rate than was stearic acid. Differences were also observed in the incorporation of these two fatty acids into complex lipids of the gallbladder mucosa. A greater portion of adsorbed linoleic acid was incorporated into triacylglycerol whereas a greater portion of stearic acid was incorporated into sphingomyelin. The significance of these findings in relation to the fatty acid composition of bile is discussed.

Animals↗

Absorption of cholesterol by the gallbladder.

To study whether cholesterol is absorbed by the gallbladder, we instilled from 1 to 300 nmoles of [4-14C]cholesterol dissolved in 1 ml of guinea pig bile into the in situ guinea pig gallbladder. The bile used in these experiments contained 7 mumole/ml bile acid, 27 nmole/ml lecithin, and 8 nmol/ml cholesterol. To this bile, we added the radioactive cholesterol, from 0 to 1 mumole/ml egg lecithin, and 100 mug/ml of bromosulfophthalein, a nonabsorbable marker. After 1 nmole [4-14C]cholesterol was instilled in bile without added lecithin, 77 +/- 8% of the radioactivity was demonstrated to be in the gallbladder wall 6 hours later. The proportion of cholesterol absorbed by the gallbladder decreased as the concentration of added lecithin or bile salts was increased. Radioautography showed radioactivity in the mucosa, and subcellular fractionation of homogenized cells by centrifugation showed cholesterol in the mitochondrial (23 +/- 4%) and microsomal (18 +/- 4%) fractions. Studies on specific activity suggested that there was net absorption of cholesterol and not merely an exchange of cholesterol in the contents for cholesterol in the wall. This study presents evidence that significant quantities of cholesterol but not cholesterol ester can be absorbed by the guinea pig gallbladder. We also found that the absorbed cholesterol can be converted to cholesterol ester and the relevance of these findings to cholesterosis in man are discussed.

Animals↗

Enhanced resistance to streptococcal infection induced in mice by cell wall mucopeptide.

The streptococcal cell wall mucopeptide when injected into mice either intraperitoneally or intravenously enhances the resitance to subsequent challenge with virulent Group A streptococci. Rabbits which are injected intravenously with solubilized mucopeptide develop a fever response which has a resemblance to that achieved with endotoxin. Mice which survive 6 to 7 weeks after challenge with virulent Group A streptococci yield at autopsy search Group A streptococci serologically identical to the challenge organisms. A preparative dose of cell walls injected into mice prior to challenge diminished this late recovery of streptococci. Group A-variant streptococci were recovered from mice which survived challenge and carried the organisms for several weeks. Filterable bacterial forms, which grew on L form media, were recovered from infected mice. The serologic type of the L forms was identical to that of the challenge organisms.

Animals↗