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1.
Nozomu Takeuchi Mitsuharu Murase Yasuharu Nomura Haruto Takase Kiyohisa Uchida 《Lipids》1987,22(8):566-571
In order to investigate the effect of hepatic cholesterol flux on biliary bile acids, Triton WR 1339 and orotic acid were
administered to rats, and the biliary cholesterol, phospholipids and bile acids were analyzed together with serum lipoproteins
and hepatic lipids. Triton, which raised serum very low density lipoprotein and lipid levels and decreased serum high density
lipoprotein liver lipid levels, increase the biliary cholic acid group/chenodeoxycholic acid group ratio (CA/CDCA) in the
bile without affecting the total amount of bile acids and the other biliary lipids. Orotic acid, which decreased serum lipid
and lipoprotein concentrations and increased liver lipid levels, increased the biliary excretion of cholesterol and phospholipids,
but produced no significant change in the total amount of bile acids and in the CA/CDCA ratio in bile. 相似文献
2.
Contrasting effects of water-soluble and water-insoluble dietary fibers on bile acid conjugation and taurine metabolism in the rat 总被引:2,自引:0,他引:2
The effect of the type of dietary fiber on the bile acid and taurine metabolism was examined in rats. Diets containing 10%
of various water-soluble fibers (citrus pectin, konjak mannan, guar gum) as compared to a fiber-free diet increased biliary
excretion of total bile acids. In contrast, water-insoluble dietary fibers (cellulose, corn bran, chitin; 10% in the diets)
as well as cholestyramine (5% in the diet) considerably, decreased bile acid excretion. Water-soluble dietary fibermediated
increases in bile acid excretion were totally attributable to increases in glycine-conjugates. Thus, these fibers greatly
increased by the bile acid glycine-to-taurine ratio (G/T). Excretio of glycine conjugates decreased more than that of taurine
conjugates in rats fed various water-insoluble dietary fibers. As a results, G/T in rats fed water-insoluble fibers was significantly
lowered as compared to G/T in animals fed a fiber-free diet. Cholestyramine did not affect the G/T ratio of bile acids. Fecal
bile acid excretion and the activities of hepatic cholesterol 7α-hydroxylase (EC 1.14.13.17) in rats fed various water-soluble
dietary fibers approximately doubled as compared to the respective values for rats fed a fiber-free diet. Whereas cholestyramine
greatly increased these parameters, water-insoluble fibers did not significantly affect them. Various water-soluble fibers
decreased hepatic concentration and urinary excretion of taurine as well as the activity of hepatic cysteine dioxygenase (EC
1.13.11.20). In contrast, water-insoluble fibers considerably increased hepatic taurine concentrations and enzyme activities.
The parameters for taurine metabolism were unaffected by cholestyramine. It was suggested that the types of dietary fiber
affected hepatic taurine synthesis and thus modified bile acid glycine/taurine ratios. 相似文献
3.
Hepatic biotransformation and the effect on bile flow of 7-ketolithocholic acid (7-oxo-3α-hydroxy-5β-cholan-24-oic acid),
in comparison to ursodeoxycholic acid, were examined in rats under conditions of continuous infusion of solutions of sodium
salts of these bile acids (1.2μmol/min/100 g body wt) for 2 hr. Both bile salts elevated the bile flow rate as well as the
bile bicarbonate concentration to a similar degree. The minor difference observed was a transient (10–20 min) and subtle drop
of bile flow during the first hour in rats given 7-ketolithocholate. In ursodeoxycholate infused rats, the major bile salt
in the bile was its taurine conjugate, although excretion of tauroursodeoxycholate dropped considerably during the second
hour. In 7-ketolithocholate infused rats, the major bile salt in the bile was again, its taurine conjugate, but ursodeoxycholate
and chenodeoxycholate and their conjugates were also excreted. In contrast to ursodeoxycholate infused rats, the drop in excretion
of taurine conjugates and the increase of glycine conjugates in rats infused with 7-ketolithocholate were more rapid. In rats
infused with 7-ketolithocholate, excretion of ursodeoxycholate and its conjugates was significantly higher than the corresponding
values for chenodeoxycholate, suggesting that 7-ketolithocholate is reduced predominatly to the 7β-epimer in this species.
However, the concentration of ursodeoxycholate and its conjugates excreted into the bile in rats infused with 7-ketolithocholate
was only 10% of that of rats infused with ursodeoxycholate, yet the magnitude of choleresis and the rise in bile bicarbonate
concentration were similar in both experiments. Therefore, it is suggested that the bicarbonate-rich bile, induced by 7-ketolithocholate
infusion, is caused mainly by 7-ketolithocholate rather than by its metabolite, ursodeoxycholate. 相似文献
4.
Kiyohisa Uchida Haruto Takase Yasuharu Nomura Takashi Satoh Hirotsune Igimi Nozomu Takeuchi 《Lipids》1997,32(4):383-390
Serum cholesterol, triglyceride and phospholipid levels, liver cholesterol concentration, bile flow, biliary cholesterol,
phospholipid and bile acid secretion rates, fecal sterol and bile acid levels and their bile acid compositions were examined
in young-old parabiotic rats and compared with those in young and old control rats and young-young parabiotic rats. Bile acid
composition was expressed in terms of the cholic acid group/chenodeoxycholic acid group (CA/CDCA) ratio. Body weight (BW)
gain decreased after parabiosis especially in old rats, but the liver weight (g/100 g BW), diet-intake, feces dry weight,
liver cholesterol concentration and fecal sterol level were almost the same in all the groups. The biliary bile acid secretion
rate was higher and the fecal bile acid level was lower in old rats than those in young rats but both the levels became comparable
with those in young rats after parabiosis of old rats with young rats. Young rats, however, showed no changes in these levels
after parabiosis. The serum cholesterol level and the biliary and fecal CA/CDCA ratios in old rats were higher than those
in young rats but decreased after parabiosis with young rats, although they were still higher than those in young rats. The
serum cholesterol level in young rats increased after parabiosis with old rats, but not after parabiosis with young rats,
and the fecal bile acid level and the CA/CDCA ratio were not changed in either case. It is concluded from these findings that
the serum cholesterol level and the CA/CDCA ratio increased with age and that these increases were prevented after parabiosis
with young rats, while young rats, although their serum cholesterol level was increased, showed no increase in the CA/CDCA
ratio after parabiosis with old rats. 相似文献
5.
The present study was undertaken to define the relationship between calcium metabolism and bile acid composition in animal
models of diet induced cholesterol and pigment gallstones. Groups of prairie dogs were fed either a control non-lithogenic
chow (N=12), a 1.2% cholesterol enriched chow (N=6, XOL) for two weeks, or a high carbohydrate diet deficient in iron (N=6,
CHO-FeD), or a high carbohydrate diet with normal iron levels (N=6, CHO) for eight weeks. Hepatic (HB) and gallbladder (GB)
bile samples were analyzed for total calcium, cholesterol, phospholipids, total bile acids (TBA), and individual bile acid
composition.
In each of the four groups, TBA concentrations were essentially similar and taurine conjugates accounted for approximately
90% of TBA in HB bile and about 98% in GB bile. In the control group, cholic acid (CA) was the predominant bile acid and comprised
76% of TBA and chenodeoxycholic (CDCA) accounted for about 13% of the total. Feeding a diet rich in cholesterol caused a significant
change in the relative concentrations of individual bile acids of hepatic bile—such that CA decreased significantly (p<0.001)
while CDCA increased by 300% (p<0.001). The changes in secondary bile acids were insignificant. An identical shift in individual
bile acid composition was noted in animals maintained on high carbohydrate diet, irrespective of iron content. Similar changes
were observed in the GB in the experimental groups.
Calcium concentrations of GB bile with or without gallstone formation showed a positive linear relationship with TBA (y=4.35+0.14X,
p<0.001) and taurochenodoxycholic acid (TCDCA) (y=15.04+0.46X, p<0.001), but an inverse relationship with taurocholic acid
(TCA) (Y=55.16−0.41X, p<0.008). However, such relationships were absent in hepatic bile. These data indicate that diet-induced
alterations in bile acid composition may modify calcium solubility or GB function, thereby contributing to the increased GB
calcium observed during cholesterol and pigment gallstone formation. 相似文献
6.
Cholesterol gallstone induction in hamsters reflects strain differences in plasma lipoproteins and bile acid profiles 总被引:4,自引:4,他引:0
Because different strains of hamsters vary in their susceptibility to gallstones, the relationship between plasma lipoproteins,
hepatic cholesterol, bile lipids and bile acid profile was examined during gallstone induction in strains of male Syrian hamsters
from Charles River Lakeview (CHR), Biobreeder F1B (BIO) and Harlan Sprague-Dawley (HAR). Gallstones were induced by feeding a purified diet containing 0.4 or 0.8% cholesterol
for 5 wk. Basal plasma total cholesterol was similar, but the hypercholesterolemia induced by dietary challenge was significantly
lower in CHR than in HAR and BIO hamsters. Cholesterol-fed CHR hamsters transported cholesterol mainly in HDL (47%), whereas
VLDL-C+IDL-C predominated in BIO and HAR hamsters, and their HDL transported only 28 and 38%, respectively. HAR hamsters accumulated
the most hepatic cholesterol, revealed the highest cholate/cheno ratio, the lowest glycine/taurine ratio and hydrophobicity
index. HAR also developed the fewest cholesterol gallstones (23%), while 64% of CHR and 58% of BIO hamsters had cholesterol
gallstones and 34% of BIO hamsters developed pigment stones. Doubling dietary cholesterol from 0.4 to 0.8% doubled the incidence
of cholesterol gallstones but exerted minimal impact on other parameters compared to strain differences. Thus, different strains
of hamsters vary considerably with respect to biliary cholesterol, bile acid profile and formation of cholesterol gallstones
associated with differences in plasma lipoprotein profiles. 相似文献
7.
Mizuho Une Erwin H. Mosbach Bertram I. Cohen Patricia May-Donath Charles K. Mcsherry 《Lipids》1985,20(4):222-226
3α-Hydroxy-7ζ-methyl-5β-cholanoic acid (7ζ-methyl-LA) was infused intravenously into bile fistula hamsters to investigate
its metabolism and effect on the bile flow as compared with lithocholic acid. Following infusion of the labeled bile acids,
bile was collected quantitatively to allow measurement of bile flow and bile acid composition. More than 80% of radioactivity
was recovered in bile within 4 hr. 7ζ-Methyl-LA and lithocholic acid in bile were present as the taurine and glycine conjugates;
no free bile acids were detected. 7ζ-Methyl-LA was neither hydroxylated nor metabolized to any measurable extent, though lithocholic
acid was 7α-hydroxylated to chenodeoxycholic acid (30–45%).
At the infusion rate at which lithocholic acid induced a severe cholestasis (264 nmol/min), 7ζ-methyl-LA did not decrease
the bile flow. In fact, the infusion of 7ζ-methyl-LA produced a mild choleresis under conditions where endogenous bile acid
excretion was not changed appreciably compared to control infusions with albumin.
It is concluded that 7ζ-methyl-LA is not metabolized in the hamster but is conjugated with taurine and glycine, and that the
introduction of a methyl group at the 7-position of lithocholic acid appears to alleviate the cholestatic effect of lithocholic
acid in the hamster. 相似文献
8.
Labeled cholesterol and its esters were injected via the portal vein into bile duct-cannulated rats, subsequent to a 7 week
regimen of either 5% safflower oil or 5% beef tallow in a hypercholesterolemic diet. Analysis of bile collected over a 6 hr
period from the safflower group showed 8.6% higher output of bile acids, 13.6% higher conversion of3H-cholesterol to bile acids and 40% higher conversion of [4-14C]cholesteryl oleate to bile acids than bile collected from the tallow group. During the 1st hr conversion of both oleyl and
linoleyl esters of14C-cholesterol to bile acids was much slower than conversion of the free3H-cholesterol to bile acids, thus eliminating these esters as preferred substrate for bile acid formation. However at 6 hr
two-thirds of the injected14C of oleyl ester was recovered in the liver, and about half of this was in the form of free cholesterol. Thus cholesterol
ester hydrolase, though inhibited by dietary cholesterol, evidently did not impose limitations on formation of free cholesterol
for subsequent oxidation reactions. Specific radioactivities were of doubtful significance because of uncertainities as to
“active” pool size. The data suggest that dietary linoleate exerts its hypocholesterolemic effect in some manner other than
ester formation and that its point of action involves stimulation of cholesterol oxidation to bile acids.
Journal Paper No. 4938 EAS, Purdue University. 相似文献
9.
Eight bile acids and 20 of their derivatives, of known purity, were compared for inhibitory effect upon oxidation of cholesterol
in vitro by rat liver mitochondria. All inhibited oxidation of14C-26-cholesterol; none inhibited oxidation of14C-1-octanoate. The α-mono-hydroxy- and α-dihydroxycholanic acids were more potent inhibitors than α-trihydroxycholanic acid
and trioxocholanic acid. Most were more potent than their derivatives. In general, the relative inhibitory potency of derivatives
was: methyl esters > free alcohols > glycine conjugates > taurine conjugates. Mitochondria from rats subjected to 4 hr alternate
light-dark periods were less susceptible to the inhibitory action of cholanate conjugates than were mitochondria from rats
under normal day-night conditions. These experiments with compounds of known purity show that the hydroxylation pattern is
the determining factor in cholanate inhibition of the cholesterol oxidation. 相似文献
10.
The bile acid concentrations in the serum, liver, bile, intestines, and feces of 3- and 19-mon-old male and female Nagase
analbuminemic (NA) rats were compared with those in Sprague-Dawley (SD) rats. There was no significant difference in the bile
acid levels between NA and SD rats. However, increased biosynthesis and pool size of cholic acid (CD) derivatives and decreased
levels of chenodeoxycholic acid (CDCA) derivatives (increased CA/CDCA ratio) were detected in male NA rats as compared to
SD rats. The CA/CDCA ratio in female NA rats was not different from that in their SD rats in the biliary bile flow, bile acid
levels in the small and large intestines, fecal bile acid excretion, bile acid concentration in the portal and systemic circulation,
and in the pool size of bile acids. The blood lipid concentrations were significantly higher in the NA rats than in the SD
rats. The hepatic levels of lipids were not significantly different between the two rat strains. In conclusion, this study
showed that metabolism of bile acids in NA rats is not significantly affected, and that the hypercholesterolemia observed
in these strains is not related to abnormalities of bile acid metabolism. 相似文献
11.
Sex differences in the effect of ethionine upon rat liver metabolism prompted our investigation into possible sex differences
in the effect of ethionine upon bile acid metabolism. The bile ducts of 24 rats, 12 male and 12 female, were cannulated. After
1 hr of bile collection, 6 rats of each sex were given ethionine, 1 mg/g body wt, by feeding tube. The bile acid composition
of the bile collected during the subsequent 4 hr was analyzed by combined thin layer and gas chromatography. Ethionine induced
a reduction in bile flow (3rd and 4th hr) and in bile acid concentration (4th hr) in female rats. The amino acid had no effect
upon bile flow but did increase biliary secretion of bile acids (1st and 2nd hr) in male rats. Cholic acid accounted for the
bulk of the reduction in total bile acid secretion in the female studies. The increase in total bile acid secretion in the
male studies involved all bile acids. The effects of ethionine upon bile acid secretion were delayed in the female studies,
immediate in the male. The changes in bile acid secretion involved only the taurine conjugates in the female studies, both
taurine and glycine conjugates in the male. There are substantial sex differences in the effect of ethionine upon bile acid
metabolism in the rat. 相似文献
12.
Effect of dietary taurine on bile acid metabolism in guinea pigs 总被引:1,自引:0,他引:1
The effect of oral administration of taurine (200–300 mg daily) on the metabolism of bile acids was studied in male guinea
pigs which have predominantly glycine conjugated bile acids. The results were summarized as follows: (a) oral administration
of taurine for 10 days increased taurine-conjugated bile acids and the ratio of glycine-to taurine-conjugated bile acids (G:T
ratio) shifted from 3.95 to 0.19; (b) in taurine fed guinea pigs, the half-life of chenodeoxycholic acid (CDC) was about 40%
shorter than that in controls and the fractional turnover rate increased by 70%; (c) the synthetic rate (mg/day/500 g body
weight) of bile acids increased from 4.28 to 7.27 by taurine feeding; (d) hepatic cholesterol 7α-hydroxylase activity was
increased 2.4-fold by taurine feeding; (e) the total pool size of bile acids did not change significantly but the amount of
lithocholic acid in the caecum and large intestine increased by about 40%; (f) neither free cholesterol nor cholesterol ester
levels in liver and serum changed significantly. Results of this study suggest that changing the G:T ratio in the bile acid
conjugation pattern may influence the rate of hepatic bile acid synthesis.
This paper is Part IX of a series entitled “Metabolism of Bile Acids”. Part VIII: ref. 12. 相似文献
13.
Previously, we have shown, in golden Syrian hamsters, that chronic feeding of ursodeoxycholic acid (UDCA), in contrast to
that of its 7α-epimer, chenodeoxycholic acid (CDCA), produced a significant increment in hepatic low-density lipoprotein (LDL)
uptake, despite similar suppression of bile acid synthesis by both bile acids. Evidence for a direct effect of this bile acid
on hepatic LDL metabolism was shownin vitro, with isolated hamster hepatocytes, suggesting that this effect was unique to UDCA and specific for receptor-mediated LDL
catabolism. The aim of the present study was to define the cellular mechanism(s) associated with this phenomenon, using male
golden Syrian hamsters. Regardless of chronic exposure of the liver to either UDCA or CDCA, acute incubation with UDCA consistently
resulted in an increase of LDL binding to isolated hepatocytes by 15 to 40%. Furthermore, chronic treatment with either UDCA
or CDCA did not result in alterations in lipoprotein particle composition. Likewise, incubation of hepatocytes with UDCA was
not associated with a change of the membrane lipid composition. In isolated liver membrane fractions, UDCA increased both
the maximum number of LDL binding sites and the affinity constant for LDL by around 35% suggesting an interaction of UDCA
with the LDL receptor, at the plasma membrane level, independent of an effect on receptor cycling. The results of the studies
support a role for UDCA in the recruitment of cryptic LDL receptors from a cellular membrane pool, possibly due to the unique
localization of UDCA in the plasma membrane lipid bilayer. 相似文献
14.
The unconjugated bile acids cholic acid, deoxycholic acid, and chenodeoxycholic acid; their glycine and taurine conjugated
glycocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, and taurochenodeoxycholic
acid; and a taurine conjugated ursodeoxycholic acid, tauroursodeoxycholic acid, were characterized through 1H and 13C NMR in aqueous media under the physiological pH region (7.4±0.1). Assignments of 1H and 13C signals of all the bile acids were made using a combination of several one- and two-dimensional, homonuclear (1H−1H) and heteronuclear (1H−13C) correlations as well as spectral editing NMR methods. Stereochemical assignment of the five-membered ring of the bile acids
is reported here for the first time. The complete characterization of various bile acids in aqueous media presented here may
have implications in the study of the pathophysiology of biliary diseases through human biliary fluids using NMR spectroscopy. 相似文献
15.
Nocturnal intragastric feeding has been shown to be an effective means to improve clinical and biochemical features in glycogen
storage disease type I (GSD-I). In this study, we investigated the fatty acid patterns in a whole plasma and in circulating
lipoproteins in patients on this therapy. The results demonstrated massive concentration of total fatty acids coupled with
higher levels of triglycerides, free cholesterol, cholesterol ester and phospholipids. This hyperlipidemia involved all fatty
acids without distinction of carbon or bond numbers. However, the increase was more pronounced for saturated than polyunsaturated
fatty acids, as was demonstrated by the ratios of both oleic acid to linoleic acid (1.91±0.40 vs 0.80±0.09 in controls) and
of ω3+ω6 to ω9 fatty acid families (0.92±0.11 vs 1.66±0.08 in controls). The fatty acid patterns in very low (VLDL), low (LDL)
and high (HDL) density lipoprotein showed substantial differences in composition, reflecting an association between an abnormal
lipoprotein pattern and essential fatty acid deficiency. Furthermore, GSD-I patients exhibited a significant increase in VLDL
(17±2 vs 47±7 mg/dl) and LDL cholesterol (124±7 vs 206±24 mg/dl), coupled with a decrease in HDL cholesterol (49±4 vs 28±3
mg/dl). These data documenting high LDL cholesterol and low HDL cholesterol associated with an increased concentration and
proportion of saturated fatty acids suggest that GSD-I patients on nocturnal intragastric feeding are at high risk for atherosclerosis
and its complications. 相似文献
16.
A simple and efficient method for the synthesis of taurine- and glycine-conjugated bile acids is described. The condensation
reaction was achieved by the simple mixing of unconjugated bile acid (1.0 eq.), taurine (2.0 eq.) (or glycinate ester), diethyl
phosphorocyanidate (1.2 eq.) in the presence of triethylamine at room temperature for 30–60 min. Sample clean-up was effected
by the use of a prepacked Sep-Pak C18 cartridge for reversed-phase solid extraction or by direct recrystallization, yielding the desired taurine and glycine conjugates
in 89–93 and 92–96% isolated yields, respectively. 相似文献
17.
E. Gerasimova N. Perova I. Ozerova V. Polessky V. Metelskaya I. Sherbakova M. Levachev S. Kulakova Yu. Nikitin T. Astakhova 《Lipids》1991,26(4):261-265
Native Chukot Peninsula residents, in contrast to Muscovites, consume a diet rich in n−3 polyunsaturated fatty acids. This
dietary peculiarity is reflected in differences in plasma lipid and apolipoprotein contents. The Chukot residents have lower
contents of total cholesterol, triglyceride, LDL (low density lipoprotein) cholesterol and apolipoprotein B, but higher HDL
(high density lipoprotein) cholesterol levels than do Muscovites. The apolipoprotein A-I levels were identical in both groups.
A higher HDL cholesterol to apolipoprotein A-I ratio was determined in the coastline Chukot residents (0.52±0.01) than in
Muscovites (0.43±0.01; p<0.01). In contrast to Muscovites, the coastline Chukot residents also had higher n−3 and lower n−6
polyunsaturated fatty acid percentages in plasma and erythrocyte lipids, and lower phosphatidylcholine and higher sphingomyelin
or phosphatidylethanolamine levels in HDL2b and HDL3. The higher HDL cholesterol levels in the plasma of the coastline Chukot residents appears to reflect the higher cholesterol-scavenging
capacity of their HDL.
We conclude from this study that the regular consumption of dietary n−3 polyunsaturated fatty acids by the coastline Chukot
residents decreased LDL cholesterol transfer from plasma to peripheral cells, and enhanced cholesterol efflux from cellular
membranes toward HDL. 相似文献
18.
Effects of bile acid feeding on hepatic deoxycholate 7α-hydroxylase activity in the hamster 总被引:1,自引:0,他引:1
In order to investigate the effects of bile acid feeding on hepatic microsomal deoxycholate 7α-hydroxylase activity, three
different bile acids were administered (0.2% w/w in chow) to hamsters for two weeks. Deoxycholate 7α-hydroxylase activity
was increased markedly by feeding of cholic acid (CA) and slightly by deoxycholic acid (DCA) Chenodeoxycholic acid (CDCA)
had little effect on the enzyme activity. Feeding each of the bile acids significantly inhibited the activity of cholesterol
7α-hydroxylase in the order CDCA≥ DCA>CA. There was no correlation between deoxycholate 7α-hydroxylase activity and cholesterol
7α-hydroxylase activity. It is concluded that the activity of deoxycholate 7α-hydroxylase is up-regulated by feeding DCA and
CA and that the mechanism seems to be different from that of cholesterol 7α-hydroxylase. The increased activity of hepatic
deoxycholate 7α-hydroxylase by CA and DCA should be beneficial in minimizing the toxic effects of DCA in the hamster. 相似文献
19.
Freshly isolated rat hepatocytes were used to examine the effects of dibutyryl cyclic AMP on the incorporation of14C-acetate and14C-cholesterol into bile acids. After an initial lag period, both precursors were incorporated into cholic and chenodeoxycholic
acids at a linear rate for the subsequent 60 min. An apparent stimulation of bile acid formation from14C-acetate by dibutyryl cyclic AMP was complicated by the concomitant inhibition of cholesterol synthesis. In experiments with14C-cholesterol, dibutyryl cyclic AMP (1 mM) increased the labeled cholic and chenodeoxycholic acids in the medium by 83 and
224%, respectively, but cellular levels of labeled bile acids were unchanged. As a result, the nucleotide stimulated the overall
incorporation of14C-cholesterol into cholic acid by 39% and into chenodeoxycholic acid by 123%. The mean ratio of labeled cholic to chenodeoxycholic
acid declined from 55∶45 in control cells to 41∶59 in cells incubated with dibutyryl cyclic AMP. The results demonstrate that
label incorporation can be used to study the regulation of bile acid synthesis in isolated hepatocytes. We propose that dibutyryl
cyclic AMP enhances bile acid production by phosphorylating, and thus stimulating the activity of, cholesterol 7α-hydroxylase,
the rate-limiting enzyme in bile acid synthesis. 相似文献
20.
Substitution of casein for soybean protein in the diet causes high degrees of hypercholesterolemia in rabbits. When rats or
humans were fed exactly the same diets, no response of the concentration of serum cholesterol to the type of protein was observed.
The hypothesis is put forward that, in rabbits, dietary casein and peptides derived from it—because of their high degree of
phosphorylation—inhibit the binding of glycine-conjugated bile acids to insoluble calcium phosphate in the intestinal lumen.
As a result, feeding of casein causes an increase in the availability of bile acids, which leads to enhanced absorption of
bile acids and cholesterol. Eventually, the concentration of serum cholesterol will be increased. In rabbits this cascade
of events occurs because these animals have a relatively low activity of intestinal alkaline phosphatase, and a high ratio
of glycine to taurine in conjugated bile acids. Unlike glycine conjugates, taurine-conjugated bile acids do not effectively
bind to the intestinal calcium-phosphate sediment. The low activity of intestinal alkaline phosphatase in rabbits secures
the high degree of phosphorylation of casein and its peptide products in the small intestine. In contrast with rabbits, rats
and humans have high activities of intestinal alkaline phosphatase and a low glycine-to-taurine ratio in conjugated bile acids.
Thus the hypothesis presented would explain why rabbits, but not rats and humans, are susceptible to dietary casein with respect
to the concentration of serum cholesterol. The relevance of the hypothesis as to the mechanisms underlying the hypercholesterolemic
effect of some other dietary proteins is discussed. 相似文献