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PubMed1988

Identification of [1-14C]pantothenic-acid-mediated modified mitochondrial proteins.

The in vivo administration of [1-14C]pantothenic acid, which is the precursor of coenzyme A, resulted in the radioactive labelling of several mitochondrial proteins in rat liver. The incorporated radioactivity could be released by glutathione or 2-mercaptoethanol. Two mitochondrial matrix proteins acetyl-CoA acetyltransferase (liver and heart), an enzyme involved in the biosynthesis or degradation of ketone bodies, and 3-oxoacyl-CoA thiolase (liver), a protein participating in fatty acid oxidation were identified as modified proteins. The radioactivity was localized exclusively in forms A1 and A2 indicating that these forms represent the modified states of the acetyl-CoA acetyltransferase protein. Kinetics of incorporation of radioactivity revealed an accumulation of the modified forms. The ratio of specific radioactivities of A2 compared to A1 was 2.41 +/- 0.15 (n = 10). After in vivo labelling with [14C]leucine, the specific radioactivity of acetyl-CoA acetyltransferase depended on the state of the enzyme protein. The unmodified enzyme exhibited a lower specific radioactivity than its modified forms suggesting different turnover rates of these proteins.

Acetyl-CoA C-Acetyltransferase↗

PubMed1987

Metabolic fate of radiolabeled palmitate in ischemic canine myocardium: implications for positron emission tomography.

Interpretation of dynamic and integrated myocardial tomograms requires elucidation of the biochemical fate of the tracer and characterization of its tissue distribution and rate of efflux. The fate of [1-11C] and [1-14C]palmitate was studied in 13 open-chest dogs during control or ischemic extracorporeal perfusion of the left circumflex coronary artery. Residue detection of myocardial radioactivity, and radio-biochemical analyses of sequential transmural biopsies and arterial and coronary venous effluent were performed for 30 min after intracoronary bolus administration of tracer. In control hearts, 10.3% of initially extracted tracer was retained in tissue (2.9% in triglyceride, 3.5% in phospholipid, and 3.9% in other lipid and aqueous fractions), 73.7% was oxidized, and 16.1% back-diffused unaltered. With ischemia (pump flow 10% of normal), 28.1% was retained (18% in triglyceride, 6.0% in phospholipid, and 4.1% in other lipid and aqueous fractions), 27.2% was oxidized, and 44.4% back diffused (p less than 0.05 compared to control). Throughout the 30-min study interval, triglyceride, diglyceride, and nonesterified fatty acid comprised a significantly greater fraction of initially extracted radioactivity in ischemic than in control hearts. Thus, during ischemia externally detected clearance rates cannot be used as a direct measure of fatty acid metabolism because of marked influences on efflux of nonmetabolized radiolabeled palmitate and the distribution of tracer retained in tissue. Quantitative measurements of specific metabolic processes by tomography will require development and validation of tracers confined to individual metabolic pathways or pools.

Animals↗

PubMed2001

The metabolism of fatty acids in human Bietti crystalline dystrophy.

PURPOSE: To investigate the role of abnormal lipid metabolism in Bietti crystalline dystrophy. METHODS: Cultured human lymphocytes and fibroblasts from patients with Bietti crystalline dystrophy (BCD) were incubated in the presence of [(14)C]18:3n-3 or [(14)C]18:2n-6. Incorporation into the cellular lipid pools and further metabolism by desaturation or elongation were monitored by thin-layer chromatography and HPLC. Results were compared with those in normal control subjects and patients with Wolman disease (WD). RESULTS: Pulse-chase experiments with labeled fatty acids in all groups showed that, after 1 hour, radioactivity was largely confined to the triacylglyceride (TG) and choline phosphoglyceride (CPG) pools. However, after several hours, radioactivity was transferred from the TG and CPG pools, some going to the serine and ethanolamine phosphoglyceride (SPG and EPG) pools. Fibroblasts from all groups showed direct transfer of fatty acids (FAs) into CPG and EPG. Incorporation of labeled FAs into the EPG pool paralleled extensive desaturation and elongation of 18:2n-6 to 22:5n-6 and 18:3n-3 to 22:6n-3. Fibroblasts from patients with WD (a lysosomal acid lipase deficiency characterized by excessive lipid accumulation), showed higher incorporation of 18:2n-6 into TGs than did normal or BCD fibroblasts. Conversely, fibroblasts from patients with BCD showed lower conversion of 18:3n-3, but not of 18:2n-6, into polyunsaturated FAs (PUFAs) than those of normal subjects or patients with WD. This was true for total FAs, CPGs, and EPGs. Similar results were found in both fibroblasts and lymphocytes; however, unlike fibroblasts, lymphocytes from normal subjects showed similar levels of incorporation of FAs into EPGs and CPGs. In contrast, incorporation of 18:3n-3 into EPGs was decreased in lymphocytes from patients with BCD. CONCLUSIONS: BCD is characterized by a lower than normal conversion of FA precursors into n-3 PUFA, whereas there is a higher than normal level of n-6 and n-3 FAs incorporation into TGs in cells from patients with WD. These findings raise the possibility that abnormal lipid metabolism associated with BCD is the result of deficient lipid binding, elongation, or desaturation in contrast to the lysosomal acid lipase deficiency found in Wolman disease.

Cells, Cultured↗

PubMed1990

Metabolism of hexacosatetraenoic acid (C26:4,n-6) in immature rat brain.

Rat brain was recently found to contain polyenoic very-long-chain fatty acids (VLCFA) belonging to the n-3 and n-6 series with four, five and six double bonds and even-carbon chain lengths from 24 to 38 [Robinson, Johnson & Poulos (1990) Biochem. J. 265, 763-767]. In the present paper, the metabolism in vivo of hexacosatetraenoic acid (C26:4,n-6) was studied in neonatal rat brain. Rats were injected intracerebrally with [1-14C]C26:4,n-6 and the labelled metabolites were examined after 4 h. Radioactivity was detected mainly in non-esterified fatty acids, with smaller amounts in other neutral lipids and phospholipids. Radiolabelled fatty acid products included C28-36 tetraenoic and C26-28 pentaenoic VLCFA formed by elongation and desaturation of the substrate, and C14-24 saturated, C16-24 monoenoic, C18-24 dienoic, C18-22 trienoic and C20-24 tetraenoic fatty acids formed from released [1-14C]acetate either by synthesis de novo or by elongation of endogenous fatty acids. The data suggest that polyenoic VLCFA are synthesized in brain from shorter-chain precursor fatty acids and undergo beta-oxidation.

Animals↗

PubMed1982

In vivo acylation of rat brain myelin proteolipid protein.

Examination of brain myelin proteins by sodium dodecyl sulfate-gel electrophoresis followed by fluorography clearly showed that both proteolipid protein (PLP) and DM-20 were acylated 24 h after the intracerebral injection of 30-day-old rats with [3H]palmitic acid. The radioactivity associated with PLP remained after purification, re-electrophoresis, and fluorography. Most of the radioactivity associated with PLP was removed when the gels were treated with hydroxylamine and then fluorographed, indicating that fatty acids were bound to PLP by ester linkage. Cleavage of purified PLP with methanolic sodium hydroxide readily released almost all protein-bound radioactivity. Thin layer chromatography of this material on both silver nitrate and reverse-phase plates provided evidence that most of the radioactivity co-migrated with methyl palmitate (77%) and methyl stearate (19%); however, some radioactivity was associated with methyl oleate (4%). Gas-liquid chromatography of the fatty acids associated with PLP distinctly revealed the presence of methyl palmitate and a detectable peak of methyl stearate.

Acylation↗

PubMed2001

The differential hepatic uptake of chylomicron remnants of different fatty acid composition is not mediated by hepatic lipase.

The hypothesis that hepatic lipase mediates the differential hepatic uptake of chylomicron remnants of different fatty acid composition, demonstrated in previous work from our laboratory, was tested by investigating the effect of antibodies to the enzyme on the uptake of remnants enriched with saturated or n-3 polyunsaturated fatty acids by the perfused rat liver. After perfusion of rat livers with polyclonal antibodies to rat hepatic lipase raised in rabbits or with rabbit non-immune serum for 15 min, [3H]oleate-labelled chylomicron remnants, derived from chylomicrons of rats given a bolus of either palm (rich in saturated fatty acids) oil or fish (rich in n-3 polyunsaturated fatty acids) oil, were added. The disappearance of radioactivity from the perfusate during 120 min and its recovery in the liver at the end of the experiments were then measured. Although the rabbit anti-rat hepatic lipase antiserum was shown to inhibit hepatic lipase activity by up to 90%, and to bind extensively to hepatic sinusoidal surfaces when added to the perfusate, radioactivity from remnants of chylomicrons from rats given a bolus of fish oil as compared with palm oil disappeared from the perfusate and appeared in the liver more rapidly in the presence both the antiserum and the non-immune serum, and the differences between the uptake of the two types of remnants were similar. We conclude, therefore, that differential interaction with hepatic lipase is not responsible for the differences in the rate of removal of chylomicron remnants of different fatty acid composition from the blood.

Animals↗

PubMed1990

Metabolism of linoleic acid in porcine epidermis.

The time course of linoleic acid metabolism in porcine epidermis has been studied in order to better evaluate the lipid transformations that accompany differentiation in this tissue. One day after intradermal injection of [U-14C]linoleic acid, most of the radioactivity in the epidermis was associated with phospholipids, triglycerides, and free fatty acids. Within 3-7 days, a portion of the radiolabel was selectively transferred to acylglucosylceramide and acylceramide fractions, after which the specific activities of all lipids fractions decreased. The results suggest that neither the lipoxygenation of linoleate nor the hydrolysis of acylceramide to form acylacid and free sphingosine are major routes of linoleate metabolism in normal epidermis. The principal pathway of linoleate metabolism in normal epidermis appears to be transfer from phospholipids to acylglucosylceramide to acylceramide. The triglyceride fraction, although minor in amount, attains an initially high specific activity, and may serve as an intermediate in linoleate transfer.

Animals↗

PubMed1985

Specificity of fatty acid acylation of cellular proteins.

Labeling of the BC3H1 muscle cell line with [3H] palmitate and [3H]myristate results in the incorporation of these fatty acids into a broad spectrum of different proteins. The patterns of proteins which are labeled with palmitate and myristate are distinct, indicating a high degree of specificity of fatty acylation with respect to acyl chain length. The protein-linked [3H]palmitate is released by treatment with neutral hydroxylamine or by alkaline methanolysis consistent with a thioester linkage or a very reactive ester linkage. In contrast, only a small fraction of the [3H]myristate which is attached to proteins is released by treatment with hydroxylamine or alkaline methanolysis, suggesting that myristate is linked to proteins primarily through amide bonds. The specificity of fatty acid acylation has also been examined in 3T3 mouse fibroblasts and in PC12 cells, a rat pheochromacytoma cell line. In both cells, palmitate is primarily linked to proteins by a hydroxylamine-labile linkage while the major fraction of the myristic acid (60-70%) is linked to protein via amide linkage and the remainder via an ester linkage. Major differences were noted in the rate of fatty acid metabolism in these cells; in particular in 3T3 cells only 33% of the radioactivity incorporated from myristic acid into proteins is in the form of fatty acids. The remainder is presumably the result of conversion of label to amino acids. In BC3H1 cells, palmitate- and myristate-containing proteins also exhibit differences in subcellular localization. [3H]Palmitate-labeled proteins are found almost exclusively in membranes, whereas [3H]myristate-labeled proteins are distributed in both the soluble and membrane fractions. These results demonstrate that fatty acid acylation is a covalent modification common to a wide range of cellular proteins and is not restricted solely to membrane-associated proteins. The major acylated proteins in the various cell lines examined appear to be different, suggesting that the acylated proteins are concerned with specialized cell functions. The linkages through which fatty acids are attached to proteins also appear to be highly specific with respect to the fatty acid chain length.

Acylation↗

PubMed1976

On the biosynthesis of plasmalogens during myelination in the rat. VIII[1]. Incorporation of 1-[1-14C] alkyl-2-acyl-3-sn-glycerophosphoethanolamine with different fatty acids.

The uptake of 14C labelled alkyl chains into the alkenyl chains of plasmalogens was estimated 12, 24, 48 and 72 h after intracerebral administration of different substrates to 14 day-old rats We used as substrates 1-[1-14C] alkyl-3-sn-glycerophosphoethanolamines, containing in the 2-position of the glycerol residue a stearoyl (substrate I), an oleoyl (II), an archidonoyl (III), a 4, 7, 10, 13, 16, 19-docosahexaenoyl (IV) or no acyl residue (substrate V, so-called lysoether phosphatide). 1) If the fatty acid in the 2-position of the substrate is a saturated one (as in experiment I), the recovery of radioactive alkyl chains is relatively high, but their desaturation is very slow and seems not to reach its maximum even after 72 h. 2) If a substrate with an unsaturated fatty acid in the 2-position is applied, the number of radioactive chains (alkyl plus alkenyl) depends on the chain length and/or the number of double bonds in the fatty acids. The desaturation of the alkyl chains, however, reaches its maximum about 48 h after application (except for substrate IV). 3) Not only is the recovery of radioactivity in the glycerophosphoethanolamine lipids by far the highest in experiment V at any time, but also the total activity of the alkenyl chains has already reached a maximum 24 h after application.

Animals↗

PubMed1986

Fatty acid-binding protein in liver and small intestine of the preruminant calf.

Cytosol obtained from differential centrifugation of homogenates from liver and small intestine mucosa was incubated with 1-[14C] oleic acid or 1-[14C] palmitic acid and filtered through Sephadex G-75. Elution profiles for both tissues showed radioactivity in two main peaks, the first corresponding to binding of fatty acid to high molecular weight proteins and the second to a protein fraction with a molecular weight of approximately 12,000 daltons. The low molecular weight fraction had high fatty acid-binding activity, which was greater for oleic than palmitic acid. The findings demonstrate the presence of fatty acid-binding protein in liver and intestinal mucosa of the preruminant calf.

Animals↗

PubMed1998

Glycolipid-protein interaction in the mechanism of signal transduction: studies with a photoactivable ganglioside analogue.

An increasing body of evidence suggests that glycolipid domains are present on the plasma membrane surface of mammalian cells and play a key role in signal transduction. We have investigated the modulation of glycolipid-protein interaction consequent to a specific event occurring at the plasma membrane. For this purpose, a new photoactivable, radioactive derivative of GM1 ganglioside, carrying a phenyldiazirine fatty acid labelled with 125I, has been used with rat cerebellar granule cells in culture. Upon incubation of photoactivable GM1 with the cells followed by illumination, several proteins become radioactive and were detectable on the two dimensional-electrophoresis, which points to their interaction with the ganglioside. Upon addition of cytotoxic doses of glutamate, known to induce indirectly the activation of protein kinase C (PKC), one of the proteins crosslinked by photoactivable GM1 in control cells of molecular mass about 92 kDa and pI about 4, was not anymore detectable; this suggests its exclusion from the glycolipid domains. On the contrary, another protein, of about 15 kDa and pI 6.5, previously not crosslinked, was interacting with the ganglioside derivative after glutamate treatment. Comparable effects were exerted by phorbol-2-myristate-3-acetate, which directly induces the activation of PKC. These results show that PKC activation, a key step of inbound trans-membrane signalling, affects the interaction between glycolipids and proteins at the plasma membrane surface, possibly within a mixed domain. The dynamic modulation of ganglioside-protein interaction may affect the involvement of glycolipid domains in membrane-located events such as signal transmission and lipid/protein sorting.

Animals↗

PubMed1979

De novo fatty acid synthesis and fatty acid elongation catalyzed by subcellular fractions from hog and human aorta.

De novo synthesis and mitochondrial elongation of fatty acids have been demonstrated in subcellular fractions from hog and human aorta. Microsomal fatty acid elongation has been shown in hog aorta. The activity catalyzing the formation of fatty acids from acetyl and malonyl CoA was associated with a high molecular weight complex in the 6 x 10(6) g x min supernatant fraction. The principal product was palmitic acid. Some myristic and stearic acids were also formed. One elongation system was associated with protein which sedimented between 4500 g x min and 150,000 g x min. It used acetyl CoA but not malonyl CoA, and NADH was the preferred reducing agent. Radioactivity from acetyl CoA was incorporated into many fatty acids. In hog aorta a second elongation system was found associated with protein which sedimented at 6 x 10(6) g x min. It used malonyl CoA preferentially as substrate and either NADH or NADPH as reducing agent.

Acetyl Coenzyme A↗

PubMed1998

Pharmacologic importance of the reversible fatty acid conjugation of budesonide studied in a rat cell line In vitro.

Functional implications of the recently described fatty acid conjugation of budesonide (BUD) (Tunek, A., K. Sjödin, and G. Hallström, Drug Metabol. Dispos. 1997;25:1311-1317; Miller-Larson, A., E. Hjertberg, H. Mattsson, M. Dahlbäck, A. Tunek, and R. Brattsand, Am. J. Respir. Crit. Care Med. 1997;155:A353 [Abstr.]) were studied in a rat cell line, Rat1, transfected with the activation protein-1 (AP-1)-controlled regulatory element (TRE) driving the reporter gene beta-galactosidase. TRE is downregulated by glucocorticosteroids (GCS) through interaction with the AP-1 complex. BUD was compared to fluticasone propionate (FP), a potent glucocorticosteroid that does not form fatty acid conjugates. The kinetics and metabolism of the GCS were studied after incubation of either 3H-BUD or 3H-FP with transfected Rat1 cells. Up to 20% of added BUD was taken up into the cells over 24 h. The great majority of the intracellular radioactivity (80-90%) consisted of lipophilic BUD conjugates. After removing extracellular 3H-GCS, the outflow of radioactivity was studied. Only free BUD and not fatty acid conjugates was detected extracellularly, suggesting that hydrolysis of the conjugates was required to release BUD from the cell. During 165 min, less BUD (about 65% of totally incorporated) was released than FP (more than 90%). In the functional studies, FP was about six times more potent than BUD in downregulating TRE after 24 h continuous exposure. However, after a 6-h pulse of GCS, the effect of BUD persisted unchanged 18 h later, whereas FP had almost lost its efficacy (P < 0.05 between the drugs). In addition, the reversible conjugation process of BUD resulted in transferable GCS effects. Medium containing released BUD from previously loaded cells mediated nearly the same downregulatory effect after addition to naive cells as did continuous treatment. No such transferable effect was seen for FP. In conclusion, the reversible fatty acid conjugation of BUD resulted in prolonged cellular retention and anti-inflammatory activity after pulse exposure in this in vitro system. This fatty acid conjugation mechanism appears to add to the beneficial pharmacologic profile of BUD.

Androstadienes↗

PubMed1986

Opsonization with antimyelin antibody increases the uptake and intracellular metabolism of myelin in inflammatory macrophages.

In most demyelinating diseases, macrophages are believed to be active agents of myelin destruction. In experimental encephalomyelitis, these cells appear to strip off and ingest the myelin lamellae, and myelin debris has been observed within the cell body. We show here in vitro conditions in which rat peritoneal macrophages phagocytose and metabolize CNS myelin lipids. Purified rat myelin, prelabeled in vivo with [14C]acetate, was incubated with preimmune serum or rabbit antiserum to rat CNS myelin and added to macrophage monolayers. Myelin opsonized with antimyelin antibodies was more readily phagocytosed and metabolized by cultured macrophages than untreated myelin or that preincubated with preimmune serum. In the presence of macrophages, levels of myelin polar lipids and cholesterol decreased, whereas radioactive cholesterol ester and triglyceride accumulated. Up to five times as much radioactive cholesterol ester and about twice as much triglyceride accumulated in macrophage cultures containing antibody-treated myelin as in cultures fed preimmune serum-treated myelin or in those incubated with untreated myelin. Both the fatty acid and the cholesterol from cholesterol ester contained radioactive label; therefore, both were derived at least partly from the radioactive myelin lipid. Antiserum to myelin purified from peripheral nerve was almost as effective as that to CNS myelin in stimulating cholesterol metabolism, whereas antiserum to galactocerebroside was about 70% as active. Antiserum to basic protein had less effect, whereas antiserum to the myelin-associated glycoprotein and proteolipid protein was inactive. Of the polar lipids, ethanolamine phosphatide was most degraded in both the antiserum- and preimmune serum-treated myelin, with the diacyl form and plasmalogen form degraded about equally. These experiments indicate that myelin-specific antibodies in inflammatory CNS lesions may participate in and stimulate macrophage-mediated demyelination.

Animals↗

PubMed1982

Stimulation of fatty acid methylation in human red cell membranes by phospholipase A2 activation.

Nonpolar methylated products comprise approximately 50% of the radioactive material extractable into chloroform/methanol after incubation of human red cell membranes with S-[methyl-3H]adenosylmethionine. One of these nonpolar products is fatty acid methyl ester. The enzyme which synthesizes fatty acid methyl ester had an apparent Km for S-adenosylmethionine of about 0.6 micro M and a Vmax of about 0.6 pmol/mg protein per 30 min. Half-maximal activity was achieved upon addition of about 20 micro M sodium oleate. Of the fatty acids tested, sodium oleate increased activity most effectively (6-fold) and arachidonic acid was ineffective. Evidence indicated that fatty acid methylation takes place on the cytoplasmic side of the plasma membrane. The reaction was demonstrable in intact cells incubated with [methyl-3H]methionine, and increased upon addition of sodium oleate. Incubation of intact cells with melittin, a potent membrane phospholipase A2 activator from bee venom, increased fatty acid methylation several-fold. Fatty acid methylation appears to be one of the consequences of phospholipase A2 action in plasma membranes.

Dose-Response Relationship, Drug↗

PubMedDate not supplied

Influence of diadenosine tetraphosphate (Ap4A) on lipid metabolism.

Diadenosine polyphosphates (Ap(x)A) are physiologically released and may be partly involved in the pathogenesis of diabetes mellitus. Ap(4)A (diadenosine tetraphosphate) leads to an increase in blood glucose while it decreases insulin levels in plasma. A possible link between Ap(x)A and diabetes mellitus-associated diseases such as insulin resistance and hyperlipidemia (plasma free fatty acids, cholesterol and its biosynthesis, triacylglycerols) has not been investigated yet. Parameters such as free fatty acid and cholesterol content in blood were determined enzymically. The biosynthesis of cholesterol and triacylglycerols was determined in HepG2 cells using the radioactive precursor [(14)C]-acetate and by using gas chromatography. Plasma free fatty acids were significantly decreased 5 and 10 min after an Ap(4)A bolus (0.75 mg kg(-1) b.w.) given to rats. Plasma cholesterol was reduced 5 and 60 min after Ap(4)A administration. LPDS (lipoprotein-deficient serum)-stimulated cholesterol biosynthesis in HepG2 cells was significantly reduced after 1 h incubation with Ap(4)A. Triacylglycerol (TAG) biosynthesis in HepG2 cells was not significantly influenced by Ap(4)A; there was just a tendency for a concentration-dependent decrease in TAG levels. In conclusion Ap(4)A as a diabetogenetic compound is not likely to be responsible for the development of insulin resistance or of hyperlipidemia. Parameters such as free fatty acids, cholesterol and triacylglycerols are not elevated by Ap(4)A, but are even decreased. Ap(4)A seems to be involved in the development of diabetes mellitus by increasing blood glucose and decreasing plasma insulin as shown earlier, but not in diabetes mellitus-associated diseases such as insulin resistance or hyperlipidemia.

Acetates↗

PubMed1999

Metabolism of n-3 and n-6 fatty acids in Atlantic salmon liver: stimulation by essential fatty acid deficiency.

Oxidation, esterification, desaturation, and elongation of [1-14C]18:2n-6 and [1-14C]18:3n-3 were studied using hepatocytes from Atlantic salmon (Salmo salar L.) maintained on diets deficient in n-3 and n-6 polyunsaturated fatty acids (PUFA) or supplemented with n-3 PUFA. For both dietary groups, radioactivity from 18:3n-3 was incorporated into lipid fractions two to three times faster than from 18:2n-6, and essential fatty acids (EFA) deficiency doubled the incorporation. Oxidation to CO2 was very low and was independent of substrate or diet, whereas oxidation to acid-soluble products was stimulated by EFA deficiency. Products from 18:2n-6 were mainly 18:3n-6, 20:3n-6, and 20:4n-6, with minor amounts of 20:2n-6 and 22:5n-6. Products from 18:3n-3 were mainly 18:4n-3, 20:5n-3, and 22:6n-3, with small amounts of 20:3n-3. The percentage of 22:6n-3 in the polar lipid fraction of EFA-deficient hepatocytes was fourfold higher than in n-3 PUFA-supplemented cells. This correlated well with our other results obtained after abdominal injection of [1-14C]18:3n-3 and [1-14C]18:2n-6. In hepatocytes incubated with [4,5-3H]-22:6n-3, 20:5n-3 was the main product. This retroconversion was increased by EFA deficiency, as was peroxisomal betaoxidation activity. This study shows that 18:2n-6 and 18:3n-3 can be elongated and desaturated in Atlantic salmon liver, and that this conversion and the activity of retroconversion of very long chain PUFA is markedly enhanced by EFA deficiency.

Animals↗

PubMed1998

Metabolism of 3H/14C-labeled 4''-deoxy-4''-epimethylaminoavermectin B1a benzoate in chickens. Identification of novel fatty acid conjugates of '4'-deoxy-4''-epimethylaminoavermectin B1a.

The metabolism of 3H/14C-labeled 4"-deoxy-4"-epimethylaminoavermectin B1a (MAB1a) benzoate, the major homologue (>/=90%) of the avermectin insecticide emamectin benzoate, was studied in laying chickens. Ten Leghorn hens (Gallus domesticus) were orally dosed once daily for 7 days (1 mg/kg of body weight/day). Eggs and excreta were collected daily, and eggs were subsequently separated into whites and yolks. Chickens were euthanized within 20 hr after the last dose, and liver, kidney, heart, muscle, fat, ovaries, gizzard, gastrointestinal tract and contents, and carcass were collected. Approximately 70 and 6% of the total administered dose were recovered in the excreta plus gastrointestinal tract and contents and in the tissues plus eggs, respectively. Two novel metabolites, i.e. the 24-hydroxymethyl derivative of the parent compound (24-hydroxymethyl-4"-deoxy-4"-epimethylaminoavermectin B1a) and the N-demethylated derivative of 24-hydroxymethyl-4"-deoxy-4"-epimethylaminoavermectin B1a (24-hydroxymethyl-4"-deoxy-4"-epiaminoavermectin B1a), were identified. In addition, eight fatty acid conjugates of each of these two metabolites, comprising 8-75% of total radioactive residues in tissues and eggs, were isolated and identified. Although this represents some of the most extensive in vivo fatty acid conjugation to a xenobiotic reported to date, potential human exposure to MAB1a residues from consumption of chicken would be extremely low, because the dosage level in this study was approximately 1000-fold greater than the MAB1a residue levels seen in crops and because the majority of the applied dose was recovered in the excreta. Based on these findings, the avian biotransformation of MAB1a differs substantially from the mammalian biotransformation.

Animals↗