Initiation of lipid peroxidation as a result of hemoglobin transformation into hemichrome induced by free fatty acids

The effects of free fatty acids on hemoglobin conversion and lipid peroxidation were studied in hemoglobin-containing liposomes (hemosomes) formed from an equimolar mixture of phosphatidylcholine (PC) and phosphatidylethanolamine (PE). It was shown that in hemosomes oxyhemoglobin is converted into hemichrome by the interaction of saturated fatty acids (arachidic, stearic, palmitic, myristic and lauric). This is accompanied by accumulation of primary and secondary products of lipid peroxidation. All fatty acids, except for lauric acid, have a stabilizing effect on lipid peroxidation in liposomes prepared from an equimolar mixture of PC and PE. The formation of lipid peroxidation products is inhibited by superoxide dismutase, D-alpha-tocopherol, D-mannitol and thiourea. The relationships between hemoglobin conversion and lipid peroxidation in hemosomes under effects of fatty acids were studied. The mechanisms of these reactions are discussed.     

Hemoglobin conversion to hemichrome under the influence of fatty acids

The effect of free fatty acids on the process of hemoglobin conversion and lipid peroxidation has been studied in model systems and erythrocytes. It has been found that methemoglobin and oxyhemoglobin are converted to the low spin oxidized form, namely, reversible hemichrome under the action of fatty acids. In the case of oxyhemoglobin, an increase in the level of active oxygen forms is observed in the system which initiates the formation of primary and secondary lipid peroxidation products. Incubation of erythrocytes with free fatty acids causes the formation of Heinz bodies and is accompanied by an increase of the lipid peroxidation level.     

Temperature adaptation in yeasts: the role of fatty acids

Studies on the yeasts Candida oleophila, Candida utilis, Lipomyces starkeyi, Rhodosporidium toruloides and Saccharomyces cerevisiae revealed the existence of three different temperature adaptation responses involving changes in fatty acid composition. These conclusions were drawn by determining the growth rates, total cellular fatty acid content, fatty acid composition, degree of unsaturation, and the mean chain length of fatty acids over a range of growth temperatures. Within temperatures permitting growth, there were no changes in the major fatty acids of any of the yeasts, but the absolute amounts and relative compositions of the fatty acids did alter. In S. cerevisiae there were temperature-induced changes in the mean fatty acid chain length, whereas in R. toruloides there were changes in the degree of unsaturation. C. oleophila, C. utilis and L. starkeyi showed both responses, depending on whether the growth temperature was above or below 20-26 degrees C. Below 20-26 degrees C temperature-dependent changes were observed in the mean chain length whereas above 20-26 degrees C there were changes in the degree of unsaturation.     

The role of membrane fatty acids in mammalian hibernation

During mammalian hibernation, cellular membranes continue to function at temperatures approaching 0 C. The molecular mechanisms that confer this capacity to the membranes are unknown but may be related to the fluidity of the membrane and to the level of unsaturated fatty acids. The basic tenets of membrane fluidity and the contribution of cholesterol, polar head groups, and fatty acids toward maintaining a fluid membrane in a liquid-crystalline state are examined in this review. It is shown that although unsaturated fatty acids can enhance membrane fluidity at low temperatures, there does not appear to be a consistent trend toward increased levels of unsatruated fatty acids during hibernation in all tissues of hibernators. Consequently, there may be some other role for the alterations in the composition of membrane fatty acids found during the hibernating cycle other than increasing membrane fluidity to permit continued activity at reduced temperatures.     

The role of fatty acids in the development and progression of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) has emerged as a serious obesity-related disorder. NAFLD encompasses a wide spectrum of hepatic derangements ranging from a surfeit of fat in the liver (steatosis) to lipid surplus accompanied by fibrosis and cellular death (nonalcoholic steatohepatitis or NASH). The most widely accepted model to explain the progression from simple NAFLD to NASH is the "two-hit hypothesis," wherein fat over accumulation per se is not sufficient to induce the progression to statohepatitis, but renders the liver more susceptible to "second hits" that, once imposed upon the steatotic liver, cause further aberrations that culminate in the development of NASH. However, in light of recent data from our laboratory and elsewhere, we propose that an increased ratio of saturated-to-unsaturated fatty acids delivered to or stored within the liver may, in part, mediate the progression from simple steatosis to NASH. The molecular mechanisms that mediate the effect of saturated fatty acids are unclear, although proinflammatory cytokines, reactive oxygen species, and endoplasmic reticulum stress may all play a role. Collectively, these data suggest that saturated fatty acids may represent an intrinsic second hit to the liver that hastens the development of NASH.     

Insights into binding of fatty acids by fatty acid binding proteins

Members of the phylogenetically related intracellular lipid binding protein (iLBP) are characterized by a highly conserved tertiary structure, but reveal distinct binding preferences with regard to ligand structure and conformation, when binding is assessed by the Lipidex method (removal of unbound ligand by hydrophobic polymer) or by isothermal titration calorimetry, a true equilibrium method. Subfamily proteins bind retinoids, subfamily II proteins bind bulky ligands, examples are intestinal bile acid binding protein (I-BABP) and liver fatty acid binding protein (L-FABP) which binds 2 ligand molecules, preferably monounsaturated and n-3 fatty acids. Subfamily III intestinal fatty acid binding protein (I-FABP) binds fatty acid in a bent conformation. The fatty acid bound by subfamily IV FABPs has a U-shaped conformation; here heart (H-) FABP preferably binds n-6, brain (B-) FABP n-3 fatty acids. The ADIFAB-method is a fluorescent test for fatty acid in equilibrium with iLBP and reveals some correlation of binding affinity to fatty acid solubility in the aqueous phase; these data are often at variance with those obtained by the other methods. Thus, in this review published binding data are critically discussed, taking into account on the one hand binding increments calculated for fatty acid double bonds on the basis of the solubility hypothesis, on the other hand the interpretation of calorimetric data on the basis of crystallographic and solution structures of iLBPs.     

On the role of catalase in the oxidation of tissue fatty acids

The role of catalase in lipid metabolism has been studied by means of a comparison of the turnover characteristics of the major lipid classes in the normal mouse with those of animals in which the catalase activity had been inhibited and blocked by aminotriazole and allylisopropylacetamide. Double isotope ratios were determined in the lipid fractions of several tissues following the injection of labeled glycerol, and a number of significant differences were identified between these treatments. Since catalase is recognized as an integral component of the peroxisomal pathway of fatty acid oxidation, these results may be taken as indicating that interruption of the process of peroxisomal beta-oxidation in this manner cause extensive perturbations of lipid metabolism in the living animal, and these perturbations extend well beyond those tissues where the predominant localization of these organelles occurs. The concept which derives from these data--that of a significant regulatory role of peroxisomes in relation to the overall balance of lipid metabolism in the animal body--is described and discussed.     

Furan fatty acids: their role in plant systems

Furan fatty acids (F-acids) are heterocyclic fatty acids having a furan ring in their structure. Most existing studies on F-acids are related to either fish or other marine animals. Even though F-acids have been detected in many plant species, not much work has been done exclusively in plants of economic importance, especially oilseed crops. This review focuses mainly on the functions and roles of F-acids in plants. In plants, they are bound to phospholipids by substituting PUFA and function as free radical scavengers suggesting their role in defense against oxidative stress. Owing to their antioxidative property F-acids are highly unstable and their photooxidative products can contribute to the flavor of edible oils.     

Control of gluconeogenesis: role of fatty acids in the alpha-adrenergic response

Phenylephrine increases hepatic gluconeogenesis for as long as it is present in the extracellular medium. This effect is accompanied by a parallel increase in oxygen consumption. No apparent stoichiometric relationship exists between the phenylephrine-stimulated respiration and the energy required to meet the demands of gluconeogenesis. In the absence of extracellular calcium, no sustained stimulation of respiration was observed and phenylephrine failed to enhance gluconeogenesis; however, acute and transient effects of the alpha-adrenergic agonist were still observable. The following observations indicate that fatty acids are not involved in the alpha-adrenergic response: (1) the effects of phenylephrine and octanoate on respiration and gluconeogenesis were found to be additive; (2) unlike phenylephrine, octanoate is capable of stimulating gluconeogenesis in calcium-depleted liver; (3) in the absence of calcium, phenylephrine was incapable of further stimulating respiration or gluconeogenesis in the presence of octanoate. It is concluded that the conditions of increased lipid mobilization and/or oxidation are not sufficient to explain the metabolic response to alpha-adrenergic agonists. Fatty acids and alpha-adrenergic stimulation share a common role of stimulating gluconeogenesis in a manner dependent on their ability to stimulate respiration; however, the additive nature of their effects and distinct calcium requirements indicate that they act to trigger different mechanisms.     

The role of dietary fatty acids in the pathology of metabolic syndrome

Dysfunctional lipid metabolism is a key component in the development of metabolic syndrome, a very frequent condition characterized by dyslipidemia, insulin resistance, abdominal obesity and hypertension, which are related to an elevated risk for type 2 diabetes mellitus. The prevalence of metabolic syndrome is strongly associated with the severity of obesity; its physiopathology is related to both genetics and food intake habits, especially the consumption of a high-caloric, high-fat and high-carbohydrate diet. With the progress of scientific knowledge in the field of nutrigenomics, it was possible to elucidate how the majority of dietary fatty acids influence plasma lipid metabolism and also the genes expression involved in lipolysis and lipogenesis within hepatocytes and adipocytes. The aim of this review is to examine the relevant mechanistic aspects of dietary fatty acids related to blood lipids, adipose tissue metabolism, hepatic fat storage and inflammatory process, all of them closely related to the genesis of metabolic syndrome.     

不饱和脂肪酸在逆境胁迫中的作用

生物膜是将细胞与环境分开的第一道屏障,是环境胁迫造成损伤的主要位点.脂肪酸是生物膜的主要组成成分,不饱和脂肪酸在决定生物膜的生理特性中具有重要作用,增加脂肪酸的不饱和程度能增加膜脂的流动性.近年来,很多研究发现,生物通过脂肪酸脱饱和维持膜的流动性来适应外界环境变化.本文主要从不饱和脂肪酸在环境温度胁迫、盐胁迫、氧化胁迫、酸碱胁迫、干旱胁迫、乙醇胁迫及铝胁迫中的作用研究进展进行了综述.     

Differential incorporation of fatty acids into and peroxidative loss of fatty acids from phospholipids of human spermatozoa

Intact human sperm incorporated radiolabelled fatty acids into membrane phospholipids when incubated in medium containing bovine serum albumin as a fatty acid carrier. The polyunsturated fatty acids were preferentially incorporated into the plasmalogen fraction of phospholipid. Uptake was linear with time over 2 hr; at this time sufficient label was available to determine the loss of fatty acids under conditions of spontaneous lipid peroxidation. Loss of the various phospholipid types, the loss of the various fatty acids from these phospholipids, and the overall loss of fatty acids were all first order. The loss of saturated fatty acids was slow with first order rate constant k₁ = 0.003 hr^?1; for the polyunsaturated fatty acids, arachidonic and docosahexaenoic acids, k₁ = 0.145 and 0.162 hr^?1, respectively. The rate of loss of fatty acids from the various phospholipid types was dependent on the type, with loss from phosphatidylethanolamine being the most rapid. Among the phospholipid types, phosphatidylethanolamine was lost at the greatest rate. Analysis of fatty acid loss through oxidation products was determined for radiolabelled arachidonic acid. Under conditions of spontaneous lipid peroxidation at 37°C under air in the absence of albumin, free arachidonic acid was found in the medium, along with minor amounts of hydroxylated derivative. All the hydroperoxy fatty acid remained in the cells. In the presence of albumin, all the hydroperoxy fatty acid was found in the supernatant bound to albumin; none could be detected in the cells. Albumin is known as a very potent inhibitor of lipid peroxidation in sperm; its action may be explained, based on these results, as binding the damaging hydroperoxy fatty acids. These results also indicate that a phospholipase A₂ may act in peroxidative defense by excising a hydroperoxy acyl group from phospholipid and providing the hydroperoxy fatty acid product as substrate to glutathione peroxidase. This formulation targets hydroperoxy fatty acid as a key intermediate in peroxidative degradation. © 1995 wiley-Liss, Inc.     

Essential fatty acids and their role in the treatment of impulsivity disorders

Essential fatty acids (EFAs) have been shown to benefit patients with depression, schizophrenia and dementia. More recently, their role in disorders characterised by impulsivity has attracted some attention. The psychiatric conditions of attention-deficit hyperactivity disorder and borderline personality disorder as well as the phenomena of deliberate self-harm and violence have been ameliorated by the supplementation of EFAs in a number of recent clinical trials. This paper summarises the burgeoning clinical and basic research indicating the existence of significant deficits of EFAs in impulsivity disorders and the supplementation studies of EFAs in these diverse conditions, all of which remain a major therapeutic challenge.