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1.
Age-related changes in Δ6 desaturation of [1-14C]α-linolenic acid and [1-14C]linoleic acid and in Δ5 desaturation of [2-14C]dihomo-γ-linolenic acid were studied in liver microsomes from Wistar male rats at various ages ranging from 1.5 to 24 mon.
Desaturase activities were expressed both as specific activity of liver microsomes and as the capacity of whole liver to desaturate
by taking into account the total amount of liver microsomal protein. Δ6 Desaturation of α-linolenic acid increased from 1.5
to 3 mon and then decreased linearly up to 24 mon to reach the same desaturation capacity of liver measured at 1.5 mon. The
capacity of liver to desaturate linoleic acid increased up to 6 mon and then remained constant, whereas microsomal specific
activity was equal at 1.5 and 24 mon of age. The capacity of liver to convert dihomo-γ-linolenic acid to arachidonic acid
by Δ5 desaturation decreased markedly from 1.5 to 3 mon. It then increased to reach, at 24 mon, the same level as that observed
at 1.5 mon. Age-related changes in the fatty acid composition of liver microsomal phospholipids at the seven time points studied
and of erythrocyte lipids at 1.5 and 24 mon were consistent with the variations in desaturation capacity of liver. In particular,
arachidonic acid content in old rats was slightly higher than in young rats whereas contents in linoleic and docosahexaenoic
acids varied little throughout the life span. The results suggest that, in liver, the activity of desaturases may be regulated
in the course of aging to maintain a constant level of polyunsaturated fatty acids in cellular membranes. 相似文献
2.
Dagny Ståhlberg 《Lipids》1995,30(4):361-364
The effects of pregnenolone-16α-carbonitrile (PCN) on hepatic metabolism of cholesterol were studied in rat liver microsomes
in order to clarify the underlying mechanisms of the PCN-induced biliary hypersecretion of cholesterol. Male Sprague-Dawley
rats were fed a diet supplemented with 0.05% of PCN for one week. The microsomal activity of 3-hydroxy-3-methylglutaryl coenzyme
A reductase, regulating cholesterol biosynthesis, decreased from 577 ± 46 (SEM) to 367 ± 38 pmol/min/mg protein compared to
the controls. Cholesterol 7 α-hydroxylase activity, governing bile acid synthesis, was 9.0 ± 1.1 pmol/min/mg protein in the
treated group and 34.8 ± 7.4 pmol/min/mg protein in the controls, a reduction of 74% (P<0.01). The acyl CoA:cholesterol acyltransferase (ACAT) activity, catalyzing the esterification of cholesterol, remained unchanged,
as did the levels of total and free cholesterol in liver homogenates and microsomes. The results of this study provide evidence
that the increase in biliary cholesterol secretion during PCN treatment is not caused by a change in ACAT activity, but can
be explained by a decreased catabolism of cholesterol to bile acids. 相似文献
3.
Steady-state fluorescence anisotropy of diphenylhexatriene and n-(9-anthroyloxy)stearic acids (n=2,12) in rat liver microsomes
showed a marked increase in the early stages of enzymatically or non-enzymatically induced lipid peroxidation. The changes
in fluorescence anisotropy occurred in parallel with the formation of thiobarbituric acid-reactive substances (TBA-RS). Parallel
to these changes, the fluorescence emitted from peroxidized microsomes increased markedly in the early stages of lipid peroxidation.
In contrast to the changes in the fluorescence anisotropy and in the formation of TBA-RS, the fluorescence showed a continuing
increase over the three hr period of lipid peroxidation. Glucose-6-phosphatase was inactivated in the early stages of lipid
peroxidation, whereas NADH-cytochrome b5 reductase underwent a slow deactivation over three hr. The apparently slow deactivation of the peripheral protein may be
explained by the formation of fluorescent substances. 相似文献
4.
The uptake of dolichol and cholesterol by perfused rat liver was studied. When these radioactive lipids were incorporated
into egg phosphatidylcholine liposomes, both dolichol and cholesterol appeared initially in the supernatant and in the microsomal
fraction and, later on, in the mitochondrial-lysosomal fraction. The lipids taken up were esterified to some extent, but no
phosphorylation of dolichol occurred. Incorporation of dolichol and cholesterol into lipoproteins increased the efficiency
of uptake, which was receptor-mediated in this case. Accumulation of these lipids occurred in lysosomes followed by a transport
to the endoplasmic reticulum (ER). Both labeled dolichol and cholesterol appeared in the bile. In the case of dolichol, the
majority of this radioactivity was not associated with the original substance itself, and probably represented lipid-soluble
catabolites. In the case of cholesterol, most of the radioactivity was associated with bile acids. It appears that, in contrast
to the receptor-mediated uptake of lipoproteins from the perfusate, the uptake of liposomal lipids involves a different mechanism.
After association with the plasma membrane, the lipids enter into the cytoplasm and are transported to the ER and later to
the lysosomes. 相似文献
5.
Lipid metabolism of male Fisher 344 rats aged 2–24 months was studied. Serum and liver cholesterol levels did not display
the age-related gradual increase seen in other rat strains. An increase in the serum plus liver cholesterol pool from 2 to
6 months was followed by a plateau through 18 months and then another increase at 24 months of age. The triglyceride pool
increased from 2 to 6 months and then remained unchanged through 24 months of age. Cholesterol synthesis from acetate decreased
50% between 2 and 9 months and fell only slightly through 24 months of age. Assay of 3-hydroxy-3-methyl glutaryl Coenzyme
A (HMG-CoA) reductase showed a similar pattern but did not decrease further after 9 months of age. Cholesterol 7α hydroxylase
activity was not significantly altered by age. These age- and strain-related differences present an opportunity for a comparative
study of the aging process using the parameters of lipid metabolism as indicators. 相似文献
6.
Fibric acid derivatives are used to treat hyperlipidemia and have wide ranging effects on lipid metabolism. The action of
these compounds on cholesterol esterification, catalyzed by acyl-coenzyme A:cholesterol acyltransferase (ACAT), has been quite
widely studied, but their effect on cholesteryl ester hydrolysis and the enzyme neutral cholesteryl ester hydrolase (nCEH)
has been largely ignored. Male rats were therefore fed for 10 d on a standard chow diet supplemented with either clofibrate
or bezafibrate, to study their effects on plasma lipid levels and hepatic cholesterol metabolism. Plasma triacyglycerols were
not significantly altered by these diets, but bezafibrate significantly lowered plasma cholesterol levels (29.7%,P<0.01). When expressed per unit weight of DNA, both fibrates reduced the hepatic content of triacylglycerol, cholesterol and
cholesteryl esters (40, 18.7, 16.5 and 66.7, 28.6, 34.2% for clofibrate and bezafibrate, respectively). ACAT activity was
significantly reduced by both drugs, but clofibrate (65% inhibition) was more effective than bezafibrate (35% inhibition).
The most dramatic effect of the diets was a marked increase in the activity of both the microsomal and the cytosolic nCEH.
When expressed on a whole liver basis, the effect of bezafibrate on the cytosolic enzyme (13.6-fold increase in activity)
was much greater than that of clofibrate (4.8-fold increase). Increases in the activity of a cytosolic protein that inhibits
the activity of nCEH were also noted, but these changes were relatively small. The results suggest that the activation of
nCEH, in combination with the inhibition in ACAT activity, contributes to a decrease in the cholesteryl ester content of the
liver which may influence the secretion of very low density lipoprotein. 相似文献
7.
The synthesis of acyl-S-pantetheine was found to occur in rat liver microsomal preparations. The reaction required ATP and
a metal ion as cofactors, a fatty acid and the reduced form of pantetheine for optimal activity. The Km for pantetheine was 0.8 mM, for ATP 0.8 mM, and for oleic acid 0.3 mM. Mg2+ (20 mM), Mn2+ (5 mM), Ca2+ (5 mM), and Fe2+ (5 mM) produced approximately equal activity when all other conditions were optimal. The characterization of the product
and other properties of the enzyme are described. The acyl-S-pantetheine formed does not act as an acyl donor in the acylation
ofsn-glycerol-3-phosphate, 1,2-diacylglycerol, or lysolecithin. 相似文献
8.
The levels of cholesterol, ubiquinone, dolichol, dolichyl-P, and total phospholipids in human lung, heart, spleen, liver,
kidney, pancreas, and adrenal from individuals from one-day-old to 81 years of age were investigated and compared with the
corresponding organs from 2 to 300 day-old rats. The amount of cholesterol in human tissues did not change significantly during
aging, but the level of this lipid in the rat was moderately elevated in the organs of the oldest animals. In human pancreas
and adrenal the ubiquinone content was highest at one year of age, whereas in other organs the corresponding peak value was
at 20 years of age, and was followed by a continuous decrease upon further aging. A similar pattern was observed in the rats,
with the highest concentration of ubiquinone being observed at 30 days of age. Dolichol levels in human tissues increase with
aging, but they increase to very different extents. In the lungs this increase is seven-fold, and in the pancreas it is 150-fold.
The elevation in the dolichol contents of rat tissues ranges from 20 to 30-fold in our material. In contrast, the levels of
the phosphorylated derivative of dolichol increased to a more limited extent, i.e., 2 to 6-fold in human tissues and even
less in the rat. These results demonstrate that the levels of a number of lipids in human and rat organs are modified in a
characteristic manner during the life-span. This is in contrast to phospholipids, which constitute the bulk of the cellular
lipid mass. 相似文献
9.
The rate of chain elongation of palmityl-CoA to stearyl-CoA in rat liver microsomes was studied in connection with the nutritional
status of the rats. The microsomal chain elongation activity, which had been decreased by starvation for 48 hr, was rapidly
increased to a high level on refeeding. The apparent Km value for malonyl-CoA in both normal and refed rats was the same,
1.2×10−4 M. Both cycloheximide and actinomycin D prevented the induction of microsomal chain elongation activity which was associated
with refeeding. In addition, the activity of acyl-CoA hydrolase and the rates of esterification of acyl-CoA into phospholipids
and neutral lipids in microsomes were not changed by the dietary alteration. These results support the conclusion that changes
of the activity of microsomal chain elongation of palmityl-CoA in various nutritional status result from a rapid synthesis
of new enzyme(s). 相似文献
10.
The fluorescent substances formed in rat liver microsomes in the course of lipid peroxidation were investigated by fluorescence
techniques. The fluorescence emitted from peroxidizing microsomes continuously increased as lipid peroxidation progressed,
while the steady-state fluorescence anisotropy increased and then reached a plateau. A similar increase was observed in the
steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in peroxidizing microsomes. The fluorescence from peroxidized
microsomes consisted of at least three species having short, middle or long fluorescence lifetimes. The lifetimes and relative
amplitudes of fluorescence were unaffected by the extent of lipid peroxidation. Both fluorescence of the chromolipids extracted
and the proteins isolated from peroxidized microsomes had the same characteristics in fluorescence lifetimes as the fluorescence
from whole peroxidized microsomes. Thus, these lipids and proteins appear to be the major biological substances responsible
for the fluorescence emanating from whole peroxidized microsomes. Furthermore, fluorescent substances formed in microsomes
seem to increase in quantity rather than change in quality as lipid peroxidation progresses. 相似文献
11.
Ludvik Peric-Golia 《Lipids》1969,4(2):147-151
A role for cholic acid in the regulation of body cholesterol levels is emphasized by the following experiment and findings.
Fifteen rats with biliary and duodenal fistulae were divided into three groups. 4-14C-cholesterol was admistered intravenously to all animals on day 1. Two groups received a duodenal infusion of either sodium
taurocholate or of cholesterol at the same time and thereafter daily. Bile samples were collected daily for 15 consecutive
days. Cholic, chenode-oxycholic acid and cholesterol were the major labeled compounds in the bile. Labeled cholic acid disappeared
from the bile of control animals after day 8 while it persisted in the group receiving unlabeled cholic acid up to day 15.
The decrease of specific radioactivity of labeled biliary cholic acid in the rats receiving unlabeled cholesterol corresponded
to that of control animals. A significant increase in the concentration of cholesterol was found in the plasma of animals
receiving cholic acid and in the liver of those receiving unlabeled cholesterol.
A preliminary report was presented at the 49th Annual Meeting of the Federation of American Societies for Experimental Biology,
Atlantic City, 1965. 相似文献
12.
A method was developed for the rapid determination of the initial velocity of the desaturation of saturated fatty acids. In
the reaction, DPNH was a more efficient electron donor than TPNH. Fatdeficient rats have a 2.5-fold greater level of acyl
desaturase per milligram of liver microsomal protein than did animals fed lab chow. Increasing the chain length of the acyl
substrate from 10∶0 to 18∶0 increases the rate of monoene formation, but 19∶0 is desaturated at a rate lower than that for
15∶0. The energy of activation (Ea) for the overall desaturation reaction has been determined for 12∶0 through 19∶0. The Ea
values for desaturation of 13∶0 and 16∶0 are markedly lowr than for the other acids. An interaction between the alkyl chain
of the substrate and polyunsaturated acids of the microsomal membrane-bound phospholipids is postulated to explain the recurring
3-carbon pattern of the relative reaction rates of the various acyl substrates. 相似文献
13.
The alkylglycerol monooxygenase catalyzing the cleavage of the ether bond in alkylglycerol resides in rat liver microsomes.
The enzyme preparation was freed of phospholipids by sodium deoxycholate treatment followed by gel filtration in the presence
of deoxycholate. The removal of phospholipids markedly decreased the alkylglycerol monooxygenase activity. The activity of
the delipidated enzyme, however, could be completely restored by the addition of phospholipid vesicles without detergent.
When individual phospholipids were added, anionic phospholipids such as phosphatidylglycerol and diphosphatidyl-glycerol were
the most effective. These findings, along with our previous observation of a similar effect of liposomes on the purified enzyme,
indicate that the amphipathic nature of the protein is responsible for the lipid dependence of enzymatic activity. 相似文献
14.
15.
Peroxidation of endogenous lipid by rat liver microsomes, coupled with oxidation of reduced nicotinamide adenine dinucleotide
phosphate (NADPH) and measured as thiobarbituric acid reactive materials, is markedly stimulated in the presence of indomethacin
[1-(p-chlorobenzyl)-5-methoxy-2-methyl-3-indole acetic acid] (0.1–1.0 mM). Concurrently, indomethacin enhances the lipolysis
of membrane phospholipid containing arachidonic acid but has no effect on the rate of O2 uptake in these samples. The system generates a rapidly developed chemiluminescense (CL), the intensity and rate of development
of which are related to indomethacin concentration. The microsomal CL generated in the presence of indomethacin is distinct
from the previously reported CL in that the time required for maximum intensity development is a matter of seconds (20–180)
rather than hours. The enhanced CL is believed to be due to an energy transfer reaction whereby a high energy species transfers
energy to the indomethacin molecule, which, in turn, decays via chemiluminescense. An enhanced chemiluminescense was also
observed when indomethacin was added to a lipoxidase system and superoxide generating system (xanthine oxidase). Based on
inhibitor studies, the rapidly developed chemiluminescense of the microsomal system requires cytochrome P-450 in addition
to NADPH and coordinated iron ions. The results indicate that the CL is related to neither hydroxyl free radical nor superoxide
anion formation. 相似文献
16.
The effect of altered methionine metabolism during pyridoxine deficiency on the activity of phosphatidyl-ethanolamine methyltransferase
(EC 2.1.1.17) and the levels of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) has been evaluated in rat liver
microsomes. Animals fed a pyridoxine-deficient diet for 7 wk displayed a fivefold increase in the hepatic tissue level of
S-adenosylhomocysteine when compared to either control or pair-fed animal counterparts. When PE methyltransferase was assayed
in vitro, a significant increase in specific activity was observed using enzyme preparations from either pair-fed or pyridoxine-deficient
rats. On the other hand, phospholipid levels did not conform to the measured enzyme activity. The level of PC in microsomes
from either pyridoxine-deficient or pair-fed animal groups was significantly lower than that determined for the control group
of rodents. However, the level of PC was noticeably lower in microsomes from pyridoxine-deficient animals than that from pair-fed
animals, which received 45% of the feed intake of the control animals. In addition, the level of PE in microsomes from pair-fed
and pyridoxine-deficient animals was significantly higher than that analyzed from the control animals, further confirming
decreased methylation of substrate to product. It is concluded that pyridoxine deficiency may alter the methylation of phospholipid
in the endoplasmic reticulum above and beyond that produced by feed restriction alone. 相似文献
17.
The acylation of lysophospholipids by rat liver acyltransferases was studied. A comparison between ester and ether lysophospholipids as substrates revealed large differences in substrate properties. For instance, oleic acid from oleoyl-CoA and arachidonic acid from arachidonoyl-CoA were not incorporated into 1-O-octadecyl-sn-glycero-3-phosphocholine under experimental conditions that allowed an optimal transfer of oleic acid and arachidonic acid to 1-O-palmitoyl-sn-glycero-3-phosphocholine. However, we observed an acyl-CoA-independent transfer of arachidonic acid from 1-O-stearoyl-2-O-arachidonoyl-sn-glycero-3-phosphoinositol to 1-O-octadecyl-sn-glycero-3-phosphocholine. 相似文献
18.
Sterol metabolism studies were carried out in rats maintained on a diet containing a polyene antibiotic, candicidin, (30 mg/kg/day)
for 2-1/2 months. Compared to the controls, the candicidintreated animals had a smaller food intake and weight gain during
this period. There was no difference between the 2 groups in serum cholesterol levels, biliary cholesterol or bile acid concentrations.
However, in the experimental group, liver cholesterol content decreased by 27% and hepatic HMG-CoA reductase increased by
36%. Candicidin administration produced an 84% increase in neutral sterol output without change in bile acid output. Cholesterol
absorption was reduced 80% by candicidin feeding. The weight of ventral prostate was reduced 33% by candicidin administration.
Prostatic HMG-CoA reductase levels were 3 times higher than those of the liver, but enzyme activity was unchanged by candicidin
treatment. 相似文献
19.
Acyl-acyl carrier protein (acyl-ACP) can serve as well as acyl-CoA as substrate of the 1-acyl-sn-glycero-3-phosphocholine (1-acyl-GPC) acyltransferase of rat-liver microsomes. The product of the acylation with either thioester
substrate is predominantly phosphatidylcholine (PC) (92–95%). The acyl-group transferred from either myristoyl-CoA or myristoyl-ACP
is located at the C-2 position of the phospholipid (PL). The apparent Km values for the myristoyl-CoA and myristoyl-ACP were
46 μM and 63 μM, and the corresponding apparent Vmax values were 1.0 and 1.6 nmol/min/mg. The rate of acylation with the acyl-ACP
was unaffected by the addition of free CoA-SH. These data suggest that acyl-CoA and acyl-ACP are transferred to 1-acyl-GPC
by the same or similar enzyme systems. 相似文献
20.
Effects of dietarytrans acids on the interconversion of linoleic acid was studied using the liver microsomal fraction of rats fed a semipurified
diet containing fat supplements of safflower oil (SAFF), hydrogenated coconut oil (HCO) at 5 and 20% levels or a 5% level
of a supplement containing 50.3% linolelaidic and 24.3% elaidic acids devoid ofcis,cis-linoleic acid (TRANS). Growth rate was suppressed to a greater extent with the animals fed the 20% than the 5% level of the
HCO-supplemented diets and still further by the TRANS diet compared to the groups fed the SAFF diets. Food intake was greater
in the groups fed the HCO than the SAFF-supplemented diets, demonstrating the marked effect of an essential fatty acid (EFA)
deficiency on feed efficiency. In contrast to an EFA deficiency produced by the HCO supplement, which stimulated the in vitro
liver microsomal biosynthesis of arachidonic acid, diets containing the TRANS supplement exacerabated the EFA deficiency and
depressed 6-desaturase activity of the liver microsomal fraction. The liver microsomal fraction of the animals receiving this
supplement also was more sensitive to fatty acid inhibition of the desaturation of linoleic acid than those obtained from
animals fed either the SAFF or HCO diets. It is suggested that dietarytrans acids alter the physical properties of the 6-desaturase enzyme system, suppressing its activity, which increases the saturation
of the tissue lipids and, in turn, the requirement for EFA or polyunsaturated fatty acids. 相似文献