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PubMed2003

Conjugated linoleic acid ameliorates viral infectivity in a pig model of virally induced immunosuppression.

We investigated the cellular and molecular immunoregulatory actions of conjugated linoleic acid (CLA) of relevance to viral disease pathogenesis and antiviral responses. To test the hypothesis that CLA ameliorates viral disease, we developed a viral challenge model by infecting pigs with type-2 porcine circovirus (PCV2). After 42 d of dietary supplementation with either soybean oil (n = 16) or CLA (n = 16), half of the pigs in each group were challenged with PCV2. We examined the effect of CLA on the development of lesions (i.e., lymphoid depletion and pneumonia) and observed the kinetics of the immune responses against PCV2. The viral infection depleted immature B cells (IgM+SWC3+) and favored proapoptotic mRNA expression profiles [i.e., suppressed B-cell leukemia/lymphoma-xl (Bcl-xl) and stimulated Bcl-2 homologous antagonist/killer (Bak)] in the external inguinal lymph nodes. B-cell depletion was more accentuated in pigs fed the control diet, whereas interleukin (IL)-2 mRNA expression was downregulated. Histopathological examination of the lungs revealed that the interstitial pneumonia tended to be more severe in infected pigs fed the control diet, which were also affected by growth retardation. CD8+ T cells were the primary cellular targets of CLA action in peripheral blood (CD8+CD29low and CD8+CD45RC+) and thymus (CD8+ and CD4+CD8+). CLA interacted with PCV2 to increase the proliferation of CD8+ T cells and to suppress PCV2-specific interferon (IFN)-gamma production in CD4+ T cells. At the molecular level, these cellular immunoregulatory properties were associated with differential patterns of peroxisome proliferator-activated receptor (alpha and gamma) mRNA expression between diets in virally infected pigs.

Animals↗
PubMed2002

Potent suppressive activity of fresh and dried peels from Satsuma mandarin Citrus unshiu (Marcorv.) on hydroperoxide generation from oxidized linoleic acid.

The effects of various extracts prepared from fresh and dried peels of Satsuma mandarin (Citrus unshiu Marcov.) on hydroperoxide generation from oxidized linoleic acid were compared under different extraction conditions. The cold-and hot-water extracts of fresh peels showed significant suppressive activity against hydroperoxide generation in a dose-dependent manner. However, the methanol or acetone extract of fresh peels did not exhibit significant suppressive effects. The commercially available ascorbic acids equivalent to their concentrations in the water extracts of fresh peels showed roughly equal antioxidative activities compared with those of the water extracts of fresh peels. Although the cold- and hot- water extracts of dried peels indicated a considerable reduction of ascorbic acid concentration, they exhibited much higher antioxidative activities than those of the fresh peels. The methanol extract of dried peels also showed significant antioxidative activities, but did not contain significant ascorbic acid. These results suggest that the fresh peels of Satsuma mandarin have potential antioxidant activities, and the drying treatment of fresh peels caused an enhancement of the antioxidant activity. The pharmacological significance of this finding is discussed.

Antioxidants↗
PubMed2002

Lipase-catalyzed acidolysis of menhaden oil with conjugated linoleic acid: effect of water content.

The effect of the water content on the lipase-catalyzed (Candida rugosa) interesterification (acidolysis) of menhaden oil with conjugated linoleic acid was studied for amounts of added water ranging from 0-4% (w/w). The rate of the acidolysis reaction increased with increasing water content, but the corresponding percentage of n-3 fatty acids liberated also increased. The implications of water content for minimization of the release of n-3 fatty acid residues while maximizing incorporation of CLA are discussed.

Alkanes↗
PubMed1998

Effect of linoleic acid on endothelial cell inflammatory mediators.

Selected lipids may influence the inflammatory cascade within the vascular endothelium. To test this hypothesis, endothelial cells were treated with linoleic acid (18:2, n - 6) for 12 hours and/or tumor necrosis factor-alpha (TNF) for 4 hours. For a combined exposure to 18:2 and TNF (18:2 + TNF), cells were first preenriched with 18:2 for 8 hours before exposure to TNF for an additional 4 hours. Exposure to 18:2 increased cellular oxidative stress, activated nuclear factor-kappaB (NF-kappaB), increased interleukin-8 (IL-8) production, and elevated intercellular adhesion molecule-1 (ICAM-1) levels. A combined exposure to 18:2+ TNF resulted in decreased NF-kappaB activation compared with TNF treatment alone. In addition, preexposure to 18:2 altered TNF-mediated IkappaB-alpha signaling. Within the first 15 minutes of a 90-minute period, cytoplasmic levels of IkappaB-alpha decreased more rapidly in cells treated with 18:2 + TNF compared with TNF, suggesting translocation and activation of NF-kappaB in cultures that were pretreated with 18:2 before TNF exposure. A combined exposure to 18:2+TNF had various effects on IL-8 production and ICAM-1 levels depending on the time of exposure. For example, 18:2 + TNF treatment increased ICAM-1 levels at 12 hours but decreased ICAM-1 levels at 24 hours compared with treatment with TNF alone. These data suggest that selected fatty acids such as 18:2 can exert proinflammatory effects and, in addition, may markedly alter TNF-mediated inflammatory events.

Cells, Cultured↗
PubMed2004

A test of Ockham's razor: implications of conjugated linoleic acid in bone biology.

The philosopher William of Ockham is recognized for the maxim that an assumption introduced to explain a phenomenon must not be multiplied beyond necessity, or that the simplest explanation is probably the correct explanation. The general truth is that conjugated linoleic acids (CLAs) are nutrients. However, the demonstration that these isomers of octadecadienoic acid protect against cancers in rodents stimulated curiosity that directed significant resources to characterize the biological functions of these fatty acids in cell and animal models. The benefits to human subjects given supplements of CLA were at best modest. The disappointing results in humans should be taken as an opportunity to critically evaluate all findings of CLA use and to consolidate the common actions of this nutrient so that future investigations focus on specific isomers and the most reasonable mechanisms. As such, the principal and consistently reported benefits of CLA have been in improving cancer outcomes, reducing body fat in growing animals, and modulating cell functions. Recognizing where related actions of CLA converge in specific disease conditions and physiologic states is how research efforts should be directed to minimize the pursuit of superfluous theories. Here, we briefly review the current biological effects of CLA and attempt to integrate their potential effect on the physiology and health of the skeletal system. Thus, the purpose of this review is to advance the science of CLA and to identify areas of research in which these nutrients affect bone metabolism and skeletal health.

Animals↗
PubMed2005

Butter naturally enriched in conjugated linoleic acid and vaccenic acid alters tissue fatty acids and improves the plasma lipoprotein profile in cholesterol-fed hamsters.

Butter, which is naturally enriched in cis-9, trans-11 conjugated linoleic acid (rumenic acid; RA) and vaccenic acid (VA), has been shown to be an effective anticarcinogen in studies with animal models; however, there has been no examination of the effects of a naturally derived source of VA and RA on atherosclerosis-related biomarkers. The current study was designed to determine the effect of a diet containing VA/RA-enriched butter on plasma lipoproteins and tissue fatty acid profiles in cholesterol-fed hamsters. Male Golden Syrian hamsters were fed diets containing 0.2% cholesterol and 20% added fat as: 1) Control, 20% standard butter (CT); 2) 5% standard butter + 15% VA/RA-enriched butter (EB); 3) 15% standard butter + 5% partially-hydrogenated vegetable oil (VO). After 4 wk, plasma lipoproteins were isolated, cholesterol quantified, and tissue fatty acid profiles determined. Tissue concentrations of VA and RA were increased by consumption of the EB diet compared with both the CT and VO diets, whereas the VO diet increased their concentration compared with the CT diet only. Total and LDL cholesterol concentrations were significantly reduced in hamsters fed EB and VO compared with CT, whereas VLDL cholesterol concentrations were reduced in hamsters fed EB compared with those fed CT and VO. HDL cholesterol concentrations did not differ among treatments. The ratio of potentially atherogenic lipoproteins [VLDL + intermediate density lipoproteins (IDL) + LDL] to antiatherogenic HDL was significantly lower in hamsters fed VA/RA-enriched butter (0.60) than in those fed either control diet (1.70) or the diet containing partially hydrogenated vegetable oil (1.04). Thus, increasing the VA/RA concentration of butter results in a plasma lipoprotein cholesterol profile that is associated with a reduced risk of atherosclerosis.

Animals↗
PubMed2003

Modulation of body fat and serum leptin levels by dietary conjugated linoleic acid in Sprague-Dawley rats fed various fat-level diets.

OBJECTIVES: In this study, we examined the effect of dietary conjugated linoleic acid (CLA) on body fat levels in Sprague-Dawley rats. METHODS: Rats were fed AIN-93G type diets containing 4%, 7%, and 10% fats with or without 1.5% CLA. RESULTS: Three weeks after the onset of the experimental period, the weights of perirenal white adipose tissue were lower in CLA-fed rats. The weights of epididymal white adipose tissue also were lower in CLA-fed rats than in control rats, but this effect disappeared with increased dietary fat level. Serum leptin levels tended to be lower in the CLA group, especially the low-fat diet group, than in the control group. There were significant positive correlations between serum leptin level and weights of perirenal and epididymal white adipose tissues in control groups, but these correlations were weaker in the CLA groups. Serum tumor necrosis factor-alpha levels also tended to be lower in CLA-fed rats, and this tendency was most remarkable in the rats fed 7% fat diets. CONCLUSION: In conclusion, dietary CLA, especially the low-fat diet, reduced body fat without hepatic injury to Sprague-Dawley rats.

Adipose Tissue↗
PubMed2001

Dietary supplementation with conjugated linoleic acid increased its concentration in human peripheral blood mononuclear cells, but did not alter their function.

The purpose of this study was to examine if conjugated linoleic acid (CLA) supplementation of diets would alter fatty acid (FA) composition and function of peripheral blood mononuclear cells (PBMC). Seventeen women, 20-41 yr, participated in a 93-d study conducted at the Metabolic Research Unit. The same diet (19, 30, and 51% energy from protein, fat, and carbohydrate, respectively) was fed to all subjects throughout the study. Seven subjects (control group) supplemented their diet with six daily capsules (1 g each) of placebo oil (sunflower) for 93 d. For the other 10 subjects (CLA group), the supplement was changed to an equivalent amount of Tonalin capsules for the last 63 d of the study. Tonalin provided 3.9 g/d of a mixture of CLA isomers (trans-10,cis-12, 22.6%; cis-11,trans-13, 23.6%; cis-9,trans-11, 17.6%; trans-8,cis-10, 16.6%; other isomers 19.6%), and 2.1 g/d of other FA. PBMC isolated on study days 30 and 90 were used to assess intracellular cytokines by flow cytometry, secreted cytokines, and eicosanoid by enzyme-linked immonosorbent assay, and FA composition by gas-liquid chromatography. After supplementation, total CLA concentration increased from 0.012 to 0.97% (P < 0.0001) in PBMC lipids, but it did not significantly alter the concentration of other FA. CLA supplementation did not alter the in vitro secretion of prostaglandin E2, leukotriene B4, interleukin-1beta (IL-1beta), or tumor necrosis factor alpha (TNFalpha) by PBMC simulated with lipopolysaccharide, and the secretion of IL-2 by PBMC stimulated with phytohemagglutinin. Nor did it alter the percentage T cells producing IL-2, interferon gamma, and percentage of monocytes producing TNFalpha. The intracellular concentration of these cytokines was also not altered. None of the variables tested changed in the control group. Our results show that CLA supplementation increased its concentration in PBMC lipids, but did not alter their functions.

Adult↗
PubMed1999

Changes in body composition in mice during feeding and withdrawal of conjugated linoleic acid.

Two experiments were conducted. In Experiment 1, 8-wk-old mice were fed control diet or diet supplemented with 0.5% conjugated linoleic acid (CLA) to study the effect of CLA on body composition (CLA: 40.8-41.1% c-9,t-11 isomer, 43.5-44.9% t-10,c-12 isomer). The data for CLA-fed mice vs. controls described parallel but significantly distinct responses for both absolute and relative changes in body fat mass (reduced in CLA-fed mice) and for relative changes in whole body protein and whole body water (both of which were increased in CLA-fed mice). In the CLA-fed mice, the effect on whole body protein appeared to precede the reduction in body fat mass. In Experiment 2, weanling mice were fed control diet or diet supplemented with 0.5% CLA for 4 wk (test group), at which time all mice were fed control diet devoid of added CLA. The test group exhibited significantly reduced body fat and significantly enhanced whole body water relative to controls at the time of diet change. Time trends for changes in relative body composition were described by parallel lines where the test group exhibited significantly less body fat but significantly more whole body protein, whole body water, and whole body ash than controls. Tissue CLA levels declined following the withdrawal of CLA from the diet. In skeletal muscle of mice fed CLA-supplemented diet, the t-10,c-12 isomer was cleared significantly faster than the c-9,t-11 CLA isomer.

Adipose Tissue↗
PubMedDate not supplied

Conjugated linoleic acid (CLA) up-regulates the estrogen-regulated cancer suppressor gene, protein tyrosine phosphatase gamma (PTPgama), in human breast cells.

BACKGROUND: Conjugated linoleic acid (CLA), a naturally occurring compound found in ruminants products, has been shown to possess anticancer properties in vivo and in vitro. There are several CLA isomers in ruminant-produced foods, among which t10, c12-CLA and c9, t11-CLA are the most potent. Protein tyrosine phosphatase gamma (PTPgamma) has been implicated as a tumor suppressor gene in kidney and lung cancers. Our previous results indicated that estradiol-17beta (E2)-induced suppression of PTPgamma may play a role in mammary tumorigenesis. MATERIALS AND METHODS: The effects of t10, c12-CLA and c9, t11-CLA on PTPgamma mRNA expression in human breast epithelial cells and stromal cells, isolated from surgical specimens of mammoplasty and breast cancer patients, were detected and quantified by RT-PCR RESULTS: The PTPgamma mRNA expression was lower in cancer than in normal breast cells. Both t10, c12-CLA and c9, t11-CLA significantly (p < 0.05) increased the PTPgamma mRNA levels in primary cultured normal breast epithelial cells, normal breast stromal cells and breast cancer epithelial cells, but not in breast cancer stromal cells. t10, c12-CLA appeared to be the most active isomer in estrogen receptor a (ERalpha)-positive human breast cancer epithelial cells. CONCLUSION: The results indicate that dietary CLA might serve as a chemo-preventive and chemo-therapeutic agent in human breast cancers by up-regulating the estrogen-regulated tumor suppressor gene, PTPgamma expression.

Breast Neoplasms↗
PubMed2004

Maternal dietary ratio of linoleic acid to alpha-linolenic acid affects the passive immunity of hatching chicks.

The objective of the current study was to examine the effect of dietary ratio of linoleic acid (LA) to alpha-linolenic acid (LNA) on the humoral immune response in laying hens and further on the passive immunity of their progeny. Thirty-two Single Comb White Leghorn laying hens, 24 wk of age, were randomly assigned to 1 of 4 diets that had LA-to-LNA ratios of 0.8, 5.4, 12.5, and 27.7, respectively, by changing the proportions of sunflower and linseed oils. After 5 wk on the experimental diets, hens were immunized intramuscularly with 1 mg of BSA, followed by 2 boosters 2 and 6 wk later. Serum and egg yolk were obtained weekly from 0 to 6 wk following the first injection of BSA. One week after the second booster, fertile eggs were collected and incubated. The sera of 11-d-old embryos and hatchlings were collected. All serum samples were stored at -20 degrees C before analysis. The results showed that dietary LA-to-LNA ratio had no effect on the total IgG and BSA-specific antibody IgG concentrations in the serum or egg yolk of laying hens. Hatchlings from hens fed the diet containing the LA-to-LNA ratio of 12.4 showed lower (P < 0.05) BSA-specific IgG titer in the serum than those from hens given the diet containing LA-to-LNA ratio of 0.8. A lower (P < 0.05) total IgG concentration was observed in hatchlings from hens fed the diet containing LA-to-LNA ratio of 12.4 compared with those from hens fed diets containing 0.8 and 5.4 of LA-to-LNA ratios. It is suggested that the dietary ratio of LA to LNA has no effect on laying hen humoral response but affects the passive immunity of hatching chicks.

Animal Nutritional Physiological Phenomena↗
PubMed2003

Conjugated linoleic acid exhibits stimulatory and inhibitory effects on prostanoid production in human endothelial cells and platelets.

In addition to their reported antitumorigenic properties, various conjugated linoleic acid (CLA) isomers have also been shown to decrease prostanoid synthesis as a result of inhibiting the cyclooxygenase (COX) enzyme. We have previously reported that several CLA isomers inhibited both platelet aggregation and formation of thromboxane A(2) (TXA(2)), a proaggregatory and vasoconstrictive agent. Since the interaction between platelets and vascular endothelial cells is essential to maintaining vascular homeostasis, we decided to investigate the effects of various CLA isomers on the production of endothelial prostacyclin (PGI(2)), a potent vasodilator and inhibitor of platelet function. Using interleukin 1-beta (IL1-beta)-stimulated human umbilical vein endothelial cells (HUVECs), we initially established that HUVECs of passage #2 should be used since these cells were most responsive to thrombin-induced conversion of endogenous arachidonic acid to PGI(2), as monitored by the formation of its stable, inactive metabolite, 6-ketoPGF(1alpha). In the first part of the study, the effects of CLA isomers in the free fatty acid form were tested. The 10(E), 12(Z)- and 9(Z), 11(E)-CLA isomers inhibited thrombin-induced 6-ketoPGF(1alpha) formation with I(50)'s of 2.6 and 5.5 microM, whereas the 9(Z), 11(Z)- and 9(E), 11(E)-CLA were ineffective at concentrations up to 60 microM. The inhibitory effect of the 10(E), 12(Z)-CLA was irreversible. Next, the effects of CLA incorporation into HUVECs on PGI(2) generation was determined. An average 8-fold stimulation of 6-ketoPGF(1alpha) formation was obtained with quiescent IL1-beta-exposed HUVECs pretreated for 18 h with 25 microM 9(Z), 11(Z)-CLA, whereas cells preincubated with the 10(E), 12(Z) isomer enhanced this eicosanoid 3-fold. Such IL1-beta-treated HUVECs prelabeled with 25 microM 9(Z), 11(Z)-CLA became refractory to thrombin stimulation, as measured by 6-ketoPGF(1alpha) production, whereas a small, statistically insignificant, inhibition was observed upon thrombin treatment of HUVECs prelabeled with the 10(E), 12(Z) isomer. Qualitative similar results were obtained with resting or thrombin-stimulated platelets containing these esterified CLA isomers indicating that these effects occur with cells that contain either the COX-1 or COX-2 isozymes. The results of this in vitro study indicate that the effects of CLA on cellular prostanoid formation in endothelial cells and platelets can be either inhibitory or stimulatory, and this seems to depend not only on the specific CLA isomer and whether or not the CLA is in the free fatty acid form or esterified into cellular lipids, but also whether cells are in the resting or stimulated state. These findings suggest that in vivo, CLA might have multiple, complex effects on vascular homeostasis.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Comparison of the effects of two low fat diets with different alpha-linolenic:linoleic acid ratios on coagulation and fibrinolysis.

Fish oils rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been demonstrated to alter coagulation and fibrinolysis variables. This study compared the effects of a traditional cholesterol-lowering diet and a similar diet, which had 50% of the linoleic acid (LA) replaced with the 18 carbon n-3 fatty acid, alpha-linolenic acid (ALA), on selected hemostatic variables. After a 2-week run-in diet with 39.5% total energy (en) from fat, 29 healthy male subjects consumed a 31.5% en fat diet with approximately 7% en from polyunsaturated fat and an ALA:LA ratio of either 1:1.2 (ALA-rich, n=15) or 1:21 (LA-rich, n=14) for 6 weeks. Blood was collected at the beginning, middle and end of test diets for analysis of Factor VIIc and VIIIc, fibrinogen, von Willebrand factor, activated protein C resistance (APC resistance), tissue plasminogen activator and plasminogen activator inhibitor type-1 activities and/or protein concentrations and platelet fatty acids. The ALA-rich diet tripled the percentage of platelet EPA, (P < 0.0005) but had little effect on coagulation and fibrinolysis. The APC ratio demonstrated increased anticoagulant activity on the ALA-rich diet (P < 0.001) only. Studies in patients with vascular pathologies are indicated to corroborate the current findings. Greater ratios of ALA:LA, achievable only with greater amounts of polyunsaturated fat, may be necessary to produce the effects demonstrated after feeding fish oils.

Adolescent↗
PubMed1980

Incorporation of linoleic acid into membrane glycerophospholipids from rat brain submitted to ischemia and hypoxia.

In the presence of ATP, Mg and CoA-SH]1-14C]linoleic acid was incorporated into membrane phospholipids (P2 fraction and synaptosomes) prepared from rat brain cortex. The relative order for linoleate incorporation was: phosphatidyl-choline greater than phosphatidylethanolamine greater than phosphatidylinositol greater than ethanolamine plasmalogen greater than phosphatidylserine. The incorporation of labeled linoleate into P2 fraction phospholipids was investigated in rats, aged 4, 16, and 90 days, after being subjected to ischemic and hypoxic conditions. With the exception of a small increase in the incorporation of the radioactivity into diacyl-GPC, little change in incorporation profile was observed with 4-day-old rats submitted to ischemic and hypoxic conditions. However, the incorporation of labeled linoleate into membrane phospholipids was decreased in 16- and 90-day-old rats being subjected to ischemic and hypoxic conditions. Among the phospholipids, the decrease in incorporation of radioactivity was most prominent with ethanolamine plasmalogens and phosphatidylinositol, although the radioactivity of phosphatidylcholine seemed to remain relative constant. The decreased incorporation activity in these two age groups was noted along with concomitant increase in the FFA content, whereas in FFA was not observed in the 4-day-old brain samples. Thus, the specific decrease in labeling of ethanolamine plasmalogens and phosphatidylinositol may be the result of increased enzymic degradation of these compounds after ischemic and hypoxic treatment. Furthermore, the decrease in incorporation of linoleate into membrane phospholipids may be due to an increase in the membrane FFA pool which subsequently gave a dilution of the labeled precursor.

Animals↗
PubMed2002

Short-term administration of conjugated linoleic acid reduces liver triglyceride concentration and phosphatidate phosphohydrolase activity in OLETF rats.

The present study explored the short-term effects of dietary conjugated-linoleic acid (CLA) on liver lipid metabolism in starved/refed Otsuka Long Evans Tokushima Fatty (OLETF) rats. Male OLETF rats (12 weeks old) were starved for 24 hours, then refed for 48 hours with either a CLA diet [7.5% CLA and 7.5% Safflower oil (SAF)] or a SAF control diet (15% SAF). The results demonstrated a 30% reduction of hepatic triglyceride (TG) concentration in the CLA group when compared to the control group. Liver cholesterol concentration was also 26% lower in the CLA fed rats. The activity of mitochondrial carnitine palmitoyltransferase, the rate-limiting enzyme of fatty acid oxidation, was moderately elevated by 1.2-fold in the livers of the CLA group when compared to the control. In contrast, phosphatidate phosphohydrolase, the rate-limiting enzyme for TG synthesis, was found to be 20% lower in the livers of the CLA-fed rats. Therefore, dietary CLA evidently lowers liver lipid concentrations through a reduced TG synthesis and enhanced fatty acid oxidation in starved/refed OLETF rats.

Animals↗
PubMed2001

Two distinct pathways of formation of 4-hydroxynonenal. Mechanisms of nonenzymatic transformation of the 9- and 13-hydroperoxides of linoleic acid to 4-hydroxyalkenals.

The mechanism of formation of 4-hydroxy-2E-nonenal (4-HNE) has been a matter of debate since it was discovered as a major cytotoxic product of lipid peroxidation in 1980. Recent evidence points to 4-hydroperoxy-2E-nonenal (4-HPNE) as the immediate precursor of 4-HNE (Lee, S. H., and Blair, I. A. (2000) Chem. Res. Toxicol. 13, 698-702; Noordermeer, M. A., Feussner, I., Kolbe, A., Veldink, G. A., and Vliegenthart, J. F. G. (2000) Biochem. Biophys. Res. Commun. 277, 112-116), and a pathway via 9-hydroperoxylinoleic acid and 3Z-nonenal is recognized in plant extracts. Using the 9- and 13-hydroperoxides of linoleic acid as starting material, we find that two distinct mechanisms lead to the formation of 4-H(P)NE and the corresponding 4-hydro(pero)xyalkenal that retains the original carboxyl group (9-hydroperoxy-12-oxo-10E-dodecenoic acid). Chiral analysis revealed that 4-HPNE formed from 13S-hydroperoxy-9Z,11E-octadecadienoic acid (13S-HPODE) retains >90% S configuration, whereas it is nearly racemic from 9S-hydroperoxy-10E,12Z-octadecadienoic acid (9S-HPODE). 9-Hydroperoxy-12-oxo-10E-dodecenoic acid is >90% S when derived from 9S-HPODE and almost racemic from 13S-HPODE. Through analysis of intermediates and products, we provide evidence that (i) allylic hydrogen abstraction at C-8 of 13S-HPODE leads to a 10,13-dihydroperoxide that undergoes cleavage between C-9 and C-10 to give 4S-HPNE, whereas direct Hock cleavage of the 13S-HPODE gives 12-oxo-9Z-dodecenoic acid, which oxygenates to racemic 9-hydroperoxy-12-oxo-10E-dodecenoic acid; by contrast, (ii) 9S-HPODE cleaves directly to 3Z-nonenal as a precursor of racemic 4-HPNE, whereas allylic hydrogen abstraction at C-14 and oxygenation to a 9,12-dihydroperoxide leads to chiral 9S-hydroperoxy-12-oxo-10E-dodecenoic acid. Our results distinguish two major pathways to the formation of 4-HNE that should apply also to other fatty acid hydroperoxides. Slight ( approximately 10%) differences in the observed chiralities from those predicted in the above mechanisms suggest the existence of additional routes to the 4-hydroxyalkenals.

Aldehyde-Lyases↗