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Exchange of palmitic acid from cytosolic proteins to microsomes, mitochondria and lipid vesicles.

The presence of two fractions with affinity for 1-14C palmitic acid was demonstrated in the 105,000 x g supernatant of rat liver homogenate by Sephadex G-75 gel filtration. The lowest molecular weight fraction was identified as fatty acid binding protein as judged by its relative elution volume in Sephadex G-75, its binding characteristics to sulfobromophthalein and palmitic acid binding inhibition by flavaspidic acid. Discontinuous sucrose gradient was used to study palmitic acid exchange from these cytosolic fractions to microsomes and mitochondria. Both fractions from rat liver were more effective than albumin in the exchange of palmitic acid to particulate material. Palmitic acid was exchanged from fatty acid binding protein to liposomes. This and perhaps other cytosolic protein/s participate in cellular fatty acid transport.

Animals↗

Role of fatty acid binding protein on hepatic palmitate uptake.

Expression of hepatic fatty acid binding protein (FABP) mRNA is regulated by growth hormone. In the absence of growth hormone, there is a 60% reduction in FABP mRNA levels (S.A. Berry, J.-B Yoon, U. List, and S. Seelig. J. Am. Coll. Nutr. 12:638-642. 1995). Previous work in our laboratory focused on the role of extracellular binding proteins in the hepatic uptake of long chain fatty acids. In the present study we were interested to determine the role of FABP in the transmembrane flux of long chain fatty acids. Using hepatocyte monolayers from control (n = 9) and hypophysectomized (n = 6) rats, we investigated the uptake of [3H]palmitate in the presence and absence of albumin. In the absence of albumin, total hepatocyte [3H]palmitate clearance rates from control (17.2 +/- 1.5 microL.mg-1 protein.s-1; mean +/- SEM; n = 9) and hypophysectomized (15.5 +/- 2.1 microL.mg-1 protein.s-1; n = 6) animals were similar (p > 0.05). In the presence of 2 microM albumin the total [3H]palmitate clearance rate from control hepatocytes (1.63 +/- 0.11 microL.mg-1 protein.s-1; n = 9) was significantly larger (40%) than from hepatocytes obtained from hypophysectomized (0.97 +/- 0.15 microL.mg-1 protein.s-1; n = 6; p < 0.01) animals. SDS-PAGE electrophoresis revealed that plasma membrane FABP levels from control and hypophysectomized animals were similar. However, there was a 49% decrease in the cytosolic FABP levels of hepatocytes isolated from hypophysectomized as compared with control animals. The decreased cytosolic FABB levels paralleled the decrease in palmitate uptake. We conclude that in the absence of extracellular binding proteins the rate-limiting step in the overall uptake of long chain fatty acids is diffusion to the cell surface. However, in the presence of albumin, the rate of palmitate uptake is determined primarily by cytosolic FABP levels.

Animals↗

The effect of vitamin A on fusion of mouse palates. I. Retinyl palmitate and retinoic acid in vivo.

C57B1 mice were given orally one, two , or three doses of ritinyl palmitate or retinoic acid on day 11, 12, 13, or 14 or pregnancy to determine 1) if it was possible to produce cleft palate at any time during palatal development of the mouse embryo, and 2) the maternal and fetal levels of vitamin A associated with the production of clefts. Whereas a single dose of either substance was sufficient to cause clefts on day 11 or day 12, three doses at 3-hour intervals were necessary to cause clefts on day 14. Most of these clefts were incomplete. Measurement of vitamin A levels in maternal serum and fetuses of dams after administration of retinyl palmitate or retinoic acid on day 11 and day 14 of pregnancy showed that transplacental passage of retinyl palmitate, retinol, and retinoic acid had taken place. Analysis of fetal serum on day 14 showed increase in levels of retinyl palmitate, retinol, and retinoic acid after dosing with retinyl palmitate, and in retinoic acid alone after dosing with retinoic acid. In both cases peak levels were observed within 3 hours. Our findings suggest that the effect of vitamin A on the developing mouse palate is direct, occurring soon after its administration, and that duration of exposure is as important as its concentration in vivo. The apparent change in sensitivity of mouse palate between day 11 and day 14 of pregnancy is discussed.

Animals↗

Palmitate turnover and its response to glucose infusion in weight-losing cancer patients.

Palmitate turnover in weight-stable control subjects (n = 4) and weight-losing patients with progressive malignant disease (n = 4) has been determined. Measurements were made after an overnight fast and during glucose infusion (3.5 mg/kg/min). Turnover rates were calculated from plateau isotopic enrichment of palmitate in plasma during a continuous infusion of 1-13C palmitate. Palmitate turnover was higher in the cancer group before (180%) and during glucose loading (170%) compared with the control group. Palmitate turnover was reduced during glucose administration by approximately 34% in both groups. Plasma concentration of insulin was decreased and of cortisol was increased in the cancer group compared with the control group before and during glucose infusion. We conclude that cancer patients with weight loss have increased rates of fatty acid turnover indicative of enhanced mobilisation of body fat stores. Altered plasma concentrations of insulin and cortisol may mediate this effect. Nonetheless, even at more advanced stages of cachexia cancer patients have normal control mechanisms for inhibiting fatty acid turnover following administration of carbohydrate.

Journal Article↗

Ascorbyl palmitate vesicles (Aspasomes): formation, characterization and applications.

Vesicles with biological activity or with a targeting function in addition to carrier properties will have an added advantage. Vesicles prepared with amphiphiles having antioxidant property may have potential applications towards disorders implicated with reactive oxygen species. Ascorbyl palmitate (ASP) was explored as bilayer vesicle forming material. It formed vesicles (Aspasomes) in combination with cholesterol and a negatively charged lipid (dicetyl phosphate). Aspasomes were prepared by film hydration method followed by sonication in which aqueous azidothymidine (AZT) solution was encapsulated in aqueous regions of bilayer. Aspasomes were obtained with all compositions containing 18-72 mol% cholesterol. Differential scanning calorimetric data of aspasome dispersion and anhydrous mixtures of ascorbyl palmitate, cholesterol and dicetyl phosphate confirm the formation of bilayered vesicles with ascorbyl palmitate. Cholesterol content in aspasome did not exhibit any relation with vesicle size, zeta potential or percent entrapment. A substantial change in release rate of azidothymidine from aspasome was noticed on varying the proportion of cholesterol. Release rate and cholesterol content in Aspasomes did not exhibit any relation. A preparation with 45 mol% of cholesterol showed maximum retardation in release rate, than other compositions. The change in capture volume with time (latency) was studied for 8 h and with such a short duration study it was difficult to predict long term stability of these vesicles. But release experiments do indicate stability up to 18 h. Percent reducing activity of aspasome was estimated by measuring the absorbance of alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) at 517 nm after addition of test antioxidant samples. These studies revealed that the antioxidant potency of ascorbyl moiety is retained even after converting ascorbyl palmitate into vesicles (Aspasomes). The antioxidant potency of Aspasomes was assessed by measuring the protection offered by this preparation against quinolinic acid induced lipoperoxidation of whole human blood in vitro, where in the lipoperoxidation was monitored by measuring thiobarbituric acid reactive substances (TBARS) levels. Aspasome rendered much better antioxidant activity than ascorbic acid. Transdermal permeation of aspasomal AZT, ASP-AZT aqueous dispersion and AZT-solution across excised rat skin was investigated in vitro using Franz diffusion cell. Permeation of aspasomal AZT was much higher than the other two preparations. However, ASP-AZT aqueous dispersion has also enhanced permeation of AZT significantly over the AZT-solution, indicating skin permeation enhancing property of ascorbyl palmitate.

Animals↗

Cholesteryl palmitate as a predictor of fetal lung maturity.

Cholesteryl palmitate was measured by thin-layer chromatography in 98 amniotic fluid samples obtained from pregnancies ranging from 15 to 40 weeks. Pregnancies complicated by diabetes mellitus or Rh sensitization were excluded. Cholesteryl palmitate concentration increased with gestational age from values less than 5 micrograms/ml at 15 weeks to maximum values of 384 micrograms/ml at term. Seventy-three patients were delivered of their infants within 24 hours of sampling. The mean concentration of cholesteryl palmitate for 55 infants without respiratory distress syndrome was 123.70 +/- 12.21 micrograms/ml (SD). For neonates that developed respiratory distress syndrome (n = 18), the mean concentration was 22.66 +/- 6.16 micrograms/ml (SD). This difference is significant (p less than 0.001). For all patients delivered, respiratory distress syndrome was not seen when the cholesteryl palmitate concentration was greater than 41 micrograms/ml (mean + 3 SD). All infants with a concentration below 38 micrograms/ml developed respiratory distress syndrome. We conclude that measurement of cholesteryl palmitate concentration in amniotic fluid might be another reliable method of assessing fetal lung maturity and may often improve specificity when compared with other tests of fetal lung maturity.

Amniotic Fluid↗

Vitamin A and vitamin A palmitate stability over time and under UVA and UVB radiation.

Vitamin A and vitamin A palmitate photostability were tested in different media. Ethanol and octyl octanoate solutions of these two vitamins, as such and with the addition of sunscreens (3,4 methylbenzilidencanfora, butyl methoxy dibenzoylmethane and octyl methoxycinnamate) or beta-carotene and butylated hydroxy toluene, were analysed spectrophotometrically after UVB or UVA irradiation. An O/W fluid emulsion with 0.5% w/w of retinyl palmitate, with and without butylated hydroxy toluene, was prepared. The oil containing the vitamin was extracted with HCl and aluminium sulfate and analysed spectrophotometrically after UVB or UVA irradiation. The fluid emulsion containing retinyl palmitate with and without butylated hydroxy toluene was stored at different temperatures and analysed every week spectrophotometrically for a month. Of the sunscreens tested butyl methoxy dibenzoylmethane showed the strongest protective action towards vitamin A and vitamin A palmitate, whereas beta-carotene did not protect either vitamin. Butylated hydroxy toluene inhibited the photodegradation of both vitamins dissolved in octyl octanoate, suggesting that oxygen may be involved in their degradation. O/W emulsion promoted slightly the degradation of vitamin A ester. Butylated hydroxy toluene protected retinyl palmitate from degradation induced by light and heat.

Butylated Hydroxytoluene↗

Ascorbic acid and ascorbic acid 6-palmitate induced oxidation in egg yolk dispersions.

The oxidation in aqueous dispersions of egg yolk powder and the influence of addition of the proposed antioxidants ascorbic acid and ascorbic acid 6-palmitate indicate that both ascorbic acid and ascorbic acid 6-palmitate propagated the oxidation of egg yolk powder dispersions. Ascorbic acid 6-palmitate was found to be more prooxidative than ascorbic acid. Moreover, it was found that addition of ascorbic acid or ascorbic acid 6-palmitate gave rise to an increase in the amount of free iron Fe(II) in the egg yolk dispersions. It is proposed that ascorbic acid and ascorbic acid 6-palmitate react with the phosvitin-Fe(III) complex found in egg yolk and release Fe(II), which subsequently propagates lipid oxidation. It appears that less oxidation occurs in egg yolk dispersions exposed to high concentrations of peroxy radicals with added ascorbic acid than egg yolk dispersions with added ascorbic acid without exposure to peroxy radicals.

Ascorbic Acid↗

The oxidation and utilization of palmitate, stearate, oleate and acetate by the mammary gland of the fed goat in relation to their overall metabolism, and the role of plasma phospholipids and neutral lipids in milk-fat synthesis.

1. Measurements were made of milk yield, mammary blood flow and arteriovenous differences of each plasma lipid fraction, and their specific radioactivities, during the infusion of [U-(14)C]stearate, [U-(14)C]oleate, [U-(14)C]palmitate and [1-(14)C]acetate into fed lactating goats. 2. Entry rates of fatty acids into the circulation were 4.2mg./min./kg. body wt. for acetate, and 0.18, 0.28 and 0.42mg./min./kg. for stearate, oleate and palmitate respectively. Acetate accounted for 23% of the total carbon dioxide produced by the whole animal, and contributed to the oxidative metabolism of the mammary gland to about the same extent. Corresponding values for each of the long-chain acids were less than 1%. 3. There were no significant arteriovenous differences of phospholipids, sterols or sterol esters, and their fatty acid composition showed no net changes during passage through the mammary gland. 4. There were large arteriovenous differences of plasma triglycerides, and their fatty acid composition showed marked changes across the gland. The proportions of palmitate and stearate fell, and that of oleate increased. 5. Arteriovenous differences of plasma free fatty acids (FFA) were small and variable, but a large fall in the specific radioactivity of each of the long-chain acids examined indicated substantial uptake of plasma FFA, accompanied by roughly equivalent FFA release from mammary tissue. The uptake of FFA was confirmed by the extensive transfer of radioactivity into milk. The FFA of milk were similar in composition and radioactivity to the milk triglyceride fatty acids, and quite unlike plasma FFA. 6. The formation of large amounts of oleic acid (18-21 mg./min.) from stearic acid was demonstrated. 7. During the terminal stages of the [(14)C]acetate infusion, milk triglyceride fatty acids of chain length C(4)-C(14) showed specific radioactivities that were 75-90% of that of blood acetate, and that of palmitate was roughly one-quarter of this value. Oleate and stearate were unlabelled. 8. The results confirmed that milk fatty acids of chain length C(4)-C(14) arise largely from blood acetate, and palmitate is derived partly from acetate and partly from plasma triglyceride, the latter fraction being almost the sole precursor of oleate and stearate.

Journal Article↗

High concentrations of vitamin A esters circulate primarily as retinyl stearate and are stored primarily as retinyl palmitate in ferret tissues.

OBJECTIVE AND METHODOLOGY: We determined the kinds and amounts of vitamin A compounds (retinol and various retinyl esters) circulating in serum and stored in liver and other selected tissues of ferrets, using high-performance liquid chromatography. RESULTS: The concentration of total retinyl esters in serum (43 +/- 1 mumol/L, mean +/- SEM) was 25 times greater than that of retinol (1.7 +/- 0.2 mumol/L). In serum, 56% of retinyl esters was retinyl stearate, 33% was retinyl palmitate, and 5% was retinyl oleate. In contrast, in liver, vitamin A was stored primarily as retinyl palmitate (51%); smaller amounts of retinyl oleate (19%) and retinyl stearate (16%) were found. In kidneys, adrenals, small intestine, adipose tissue, skin, stomach, and eyes, retinyl palmitate was also the predominant retinyl ester, followed by retinyl stearate. In colon, lungs, and bladder, equal amounts of retinyl palmitate and retinyl stearate were observed. Other retinyl esters present in smaller amounts in most of these tissues were retinyl oleate, retinyl linoleate and/or -myristate, retinyl heptadecanoate, retinyl arachidonate, and retinyl laurate. CONCLUSIONS: Thus, the primary form of vitamin A that circulates in the blood of ferrets is retinyl stearate, whereas the primary storage form of the vitamin in tissues is retinyl palmitate. Concentrations of total vitamin A in ferret serum and other tissues were 3-73 times greater than those reported for their corresponding human tissues.

Animals↗

Olestra ingestion and retinyl palmitate absorption in humans.

This study examined the effect of olestra, a zero-calorie fat replacement, on the absorption of retinyl palmitate in humans. After a 30-d adaptation period during which they consumed 10 g olestra/d in potato chips under free-living conditions, 68 healthy male subjects were housed in a metabolic ward and given a single dose of retinyl palmitate (0.33 RDA) containing a trace amount of 3H-retinyl palmitate with a breakfast that contained 0, 8, 20 or 32 g of olestra and about 38 g of triglyceride. Blood was collected at defined intervals for 48 h and plasma analyzed for 3H-retinyl esters by HPLC and liquid scintillation spectrometry. There was no significant effect on retinyl palmitate absorption as determined from the area under the plasma 3H-retinyl esters concentration-time curve. However, an area under the plasma concentration-time curve in the 32-g olestra group that was 81% (mean value) or 70% (median value) of the area under the curve for the placebo group suggested that olestra may have affected retinyl palmitate absorption. Inclusion or exclusion of 13 high responders did not change the results.

Adult↗

An alpha-adrenoceptor-mediated mechanism of hypoactivity induced by beta-amyrin palmitate.

Inhibitory effects of beta-amyrin palmitate in locomotor activity of mice were studied by combining this compound with alpha-adrenergic agonists or antagonists and a dopaminergic agonist. beta-Amyrin palmitate (2.5, 5.0 and 10.0 mg kg-1, i.p.) decreased locomotor activity of mice in a dose-dependent manner. It enhanced hypoactivity of mice treated with clonidine (0.025 mg kg-1, i.p.) and antagonized hyperactivity produced by phenylephrine (40 micrograms, i.c.v.). The inhibitory action of beta-amyrin palmitate was not affected by yohimbine (1.5 mg kg-1, i.p.), but was potentiated by prazosin (0.75 mg kg-1, i.p.). When combined with a dopaminergic agonist, apomorphine (2.0 mg kg-1, i.p.), beta-amyrin palmitate (5.0 and 10.0 mg kg-1, i.p.) did not affect locomotor stimulation produced by apomorphine. These results suggest that beta-amyrin palmitate might inhibit alpha 1-adrenoceptors.

Adrenergic alpha-Agonists↗

Effect of prepubertal retinyl palmitate treatment on uterine development and subsequent uterine capacity in swine.

The effect of prepubertal retinyl palmitate treatment on uterine development and uterine capacity was determined. Gilts remained intact or were unilaterally hysterectomized-ovariectomized (UHO) on d 28, 84, or 112 of age. Starting at birth, half of the gilts in each UHO group were treated with retinyl palmitate (14,000 IU.kg-1.wk-1) and half received control carrier solution. All intact gilts received control carrier solution. Blood samples (d 28, 56, 84, and 112 of age) were analyzed for retinoid and retinol-binding protein (RPB). At UHO, part of the excised uterine horn was processed for morphometric analysis of the uterine wall, and tissues were incubated in minimal essential medium with [3H]leucine to assess total protein and RBP production. After puberty, gilts were mated and then killed on d 44 to 47 of pregnancy; uterine length, number of corpora lutea and fetuses, and fetal, placental, and empty uterine weights were recorded. Endometrial tissues were incubated in minimal essential medium with [3H]leucine, and nondialyzable radioactivity, acid phosphatase, and RBP production were measured. During the prepubertal period, retinyl palmitate treatment decreased (P < .05) myometrial area (longitudinal and circular), but it had no effect on other components of the uterine wall or production of nondialyzable radioactivity or secretion of RBP by uterine tissue. During pregnancy, prepubertal retinyl palmitate treatment increased (P < .05) uterine length but had no effect on uterine weight, number of fetuses, placental or fetal weights, or endometrial production of nondialyzable radioactivity, acid phosphatase, or RBP. Therefore, prepubertal retinyl palmitate treatment at the dosage administered had no effect on uterine capacity.

Acid Phosphatase↗

A liquid chromatographic method for analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in medical food using matrix solid-phase dispersion in conjunction with a zero reference material as a method development tool.

A liquid chromatographic method is described for analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in medical food. The vitamins are extracted from medical food without saponification by matrix solid-phase dispersion and chromatographed by normal-phase chromatography with fluorescence detection. Retinyl palmitate and all-rac-alpha-tocopheryl acetate are quantitated isocratically with a mobile phase of 0.125% (v/v) and 0.5% (v/v) isopropyl alcohol in hexane, respectively. Results compared favorably with label declarations on retail medical foods. Recoveries determined on an analyte-fortified zero reference material for a milk-based medical food averaged 98.3% (n = 25) for retinyl palmitate spikes and 95.7% (n = 25) for all-rac-alpha-tocopheryl acetate spikes. Five concentrations were examined for each analyte, and results were linear (r2 = 0.995 for retinyl palmitate and 0.9998 for all-rac-alpha-tocopheryl acetate) over the concentration range examined, with coefficients of variation in the range 0.81-4.22%. The method provides a rapid, specific, and easily controlled assay for analysis of retinyl palmitate and all-rac-alpha-tocopheryl acetate in fortified medical foods.

Chromatography, Liquid↗

[Retinol Acetate Reference Standard (Control 971) and Retinol Palmitate Reference Standard (Control 971) of National Institute of Health Sciences].

The "Retinol Acetate Reference Standard (Control 971)" and "Retinol Palmitate Reference Standard (Control 971)" of National Institute of Health Sciences using the assay of vitamin A ester were prepared. The proposed materials were evaluated in collaboration with four laboratories. Analytical data obtained were as follows. 1) The purities of retinol acetate and retinol palmitate measured by HPLC were 99.9 +/- 0.06% and 94.5 +/- 0.06%, respectively. 2) ultraviolet spectrum of retinol acetate and retinol palmitate showed the lambda max at 326-327 nm. 3) The difference in relative extinction of retinol acetate and retinol palmitate at 300 nm, 310 nm, 320 nm, 330 nm, 340 nm and 350 nm are within the range provided in JPXIII. 4) The contents of retinol acetate and retinol palmitate were 52,000 IU/g and 52,200 IU/g, respectively. Based on the above results, these proposed materials were authorized to be the Reference Standards of the National Institute of Health Sciences.

Diterpenes↗

Retinyl palmitate supplementation by inhalation of an aerosol improves vitamin A status of preschool children in Gondar (Ethiopia).

We report successful vitamin A supplementation by inhalation of retinyl palmitate in a placebo-controlled pilot study in twenty-five preschool children (2-5 years of age) in the rural district of Gondar, Ethiopia. Preschool children (n 161) were randomly selected from 220 households. Out of this cohort, twenty-five children were randomly assigned to each of two treatment groups: one receiving retinyl palmitate by inhalation of two puffs of an aerosol containing 1 mg (3000 IU) per delivery to give a total of 2 mg (6000 IU); and the other receiving an aerosol without retinyl palmitate. Both treatments were administered every 2 weeks for 3 months. Serum retinol and retinol-binding protein concentrations in the vitamin A-treated group were 0.68 (SD 0.31) mumol/l and 59.4 (SD 24.2) mg/l before and 1.43 (SD 0.46) mumol/l (P < 0.01) and 97.3 (SD 31.2) mg/l (P < 0.05) 3 months after supplementation with retinyl palmitate, suggesting that this novel method of delivery of retinyl palmitate by inhalation is effective in improving vitamin A status.

Administration, Inhalation↗

[Biological synthesis of L-ascorbyl palmitate].

Biological synthesis of L-Ascorbyl Palmitate in organic system were studied in this text. The contradiction between conversion of vitamin C and concentration of L-Ascorbyl Palmitate were resolved. High conversion of vitamin C and concentration of L-Ascorbyl Palmitate were obtained by Novo435. A series of solvents(log P from -0.24 to 3.5 )were investigated for the reaction,and acetone was found to be the most suitable from the standpoint of the enzyme activity and solubility of L-ascorbic. And the equilibrium of the reaction was affected by the addition of the molecular sieves and temperature. Reaction carried out at 60 degrees C and with 20% 0.4nm molecular sieves is good for the enzyme to keep its activity and for making the equilibrium go to the product. With 1.094 g palmitic acid, 0.107 g vitamin C and 0.020 g Novo435, rotate rate of 200 r/min, the conversion of ascorbic reached 80% and the concentration of L-ascorbyl palmitate is 20 g/L after 48 h. Furthermore, reaction batch of Novo435 and substrates recycle were observed, the result indicated that Novo435 may used 4-5 times continuously with high conversion. And 6-O-unsaturated acyl L-ascorbates were synthesized through Novo435 condensation of ascorbic acid and various unsaturated fatty acids with high conversion in this text.

Ascorbic Acid↗

[Comparison of the effects of pipothiazine palmitate and fluphenazine decanoate. Results of a multicenter double-blind trial].

Fluphenazine decanoate and pipothiazine palmitate were compared concerning their effect and side-effects. 61 schizophrenic patients were treated up to 6 months in a multicenter double-blind trial. Assessments were made on day 0 and after 5, 10, 17 and 22 weeks of treatment using the AMP system. Pipothiazine palmitate was injected every 4th week and fluphenazine decanoate every 3rd week. The most often applied dosage was 100 mg pipothiazine palmitate and 25 or 37.5 mg fluphenazine decanoate. Data analysis of the AMP system at the symptom level showed the better antipsychotic effect of pipothiazine palmitate. A comparison between the two groups by means of analysis of covariance at the syndrome level showed no statistical significant differences between the effects of fluphenazine decanoate and pipothiazine palmitate.

Antipsychotic Agents↗