Liver trans fatty acids

Trans fatty acids in liver of rats Silica AgNOj argentation 15... 

Humans produce about 1 gram of cholesterol daily in the liver. Dietary cholesterol is consumed through food. High cholesterol foods are associated with saturated fats and trans-fatty acids (commonly called trans fats). Dietary cholesterol comes from animal products (plants contain minute amounts of cholesterol) such as meats and dairy products. Table 26.1 shows the amount of cholesterol in common foods. 

There are other cases of inhibition of lipid enzymatic pathways by trans fatty acid isomers. The above reported mono-14 -trans isomer of arachidonic acid is inhibitor of the synthesis of thromboxane B2 and, therefore, can prevent rat platelet aggregation [52]. The transformation of mono-trans isomers of linoleic acid by rat liver microsomes showed that the 9-cis,12-trans isomer is better desaturated, whereas the 9-trans, 2-cis isomer (Scheme 6.1) is better elongated [53]. 

During the 1980s, research indicated that trans fatty acids have an effect on blood cholesterol similar to that of saturated fats, although study results vary. Several studies reported that trans fatty acids raise the levels of LDL-cholesterol, low-density lipoproteins containing cholesterol that can accumulate in the arteries. Some studies also report that trans fatty acids lower HDL-cholesterol, high-density lipoproteins that carry cholesterol to the liver to be excreted. 

In heart, liver, and brain, trans fatty acids occm mainly in membrane phospholipids. The position of the double bond as well as the conformation of the carbon chain may determine the pattern of trans fatty acid esterification in phospholipids, but there is evidence that trans- 8 fatty acids are preferentially incorporated into position 1 of the phospho-acylgly-cerols, as are saturated fatty acids in contrast, oleic acid is randomly distributed. 

Testosterone (T.) derivatives for clinical use. T. esters for im. depot injection are T. propionate and T. heptanoate (or enanthate). These are given in oily solution by deep intramuscular injection. Upon diffusion of the ester from the depot, esterases quickly split off the acyl residue, to yield free T. With increasing lipophilicity, esters will tend to remain in the depot, and the duration of action therefore lengthens. A T. ester for oral use is the undecanoate. Owing to the fatty acid nature of undecanoic acid, this ester is absorbed into the lymph, enabling it to bypass the liver and enter, via the thoracic duct, the general circulation. 17-0 Methyltestosterone is effective by the oral route due to its increased metabolic stability, but because of the hepatotoxicity of Cl 7-alkylated androgens (cholestasis, tumors) its use should be avoided. Orally active mesterolone is 1 a-methyl-dihydrotestosterone. Trans-dermal delivery systems for T. are also available. 

In the intestinal mucosal cells, /3-carotene is cleaved via an oxygenase (an enzyme that introduces molecular 02 into organic compounds) to frans-retinal (aldehyde form of trans-retinol, as shown in Table 6.2), which in turn is reduced to frans-retinol, vitamin Av Retinol is then esterified with a fatty acid, becomes incorporated into chylomicrons, and eventually enters the liver, where it is stored in the ester form until it is required elsewhere in the organism. The ester is then hydrolyzed, and vitamin Ax is transported to its target tissue bound to retinol-binding protein (RBP). Since RBP has a molecular weight of only 20,000 and would be easily cleared by the kidneys, it is associated in the bloodstream with another plasma protein, prealbumin. 

The liver has a variety of functions in lipid metabolism (7.) uptake, oxidation and transformation of free fatty acids, (2.) synthesis of plasma lipoproteins, (3.) trans-... 

Monooxygenase metabolism of essential fatty acids has received comparatively little attention. DiAugustine and Fonts found that in liver microsomes, linoleic acid, linolenic acid and arachidonic acid induced spectral changes of type I, which are associated with metabolism, but the products were not identified [394]. These polyunsaturated fatty acids could be expected to be wl- and w2-hydroxylated like their saturated counterparts and to be transformed into hydroxylated cis,trans conjugated products by chemical peroxidation (autooxidation) as discussed above. Recent studies show that cytochrome P-450 can metabolise polyunsaturated fatty acids to a large extent by epoxidation. The epoxides are rapidly hydrolysed to vicinal diols by microsomal or soluble enzymes. 

The apolipoproteins, along with the lipids which are bonded over hydrophilic interactions, form the. so-called lipoproteins. Chylomicrons are responsible for the uptake in the blood and tran.spori of the fat contained in food. In the blood apolipoprolein Cll is taken up from high-density lipoproteins (HDLsl which are activated by the lipoprotein lipase. With their help the fats are hydrolyzed in the chylomicrons. The free fatty acids are now available for the body cells or bind with the albumins of the blood. The remaining particles are completely degraded in the liver. 

In fact a fatty acid does not have to have two or more double bonds in order to serve as a substrate for a 5-desaturase. A number of different cis and trans monoenoic acids are desaturated at position 5 (Lemarchal and Bornens, 1968 Mahfouz and Holman, 1980 Pollard eta/., 1980a). When seven different methyl branched isomers of 8,11,14-20 3 were used as substrates for desaturation with rat liver microsomes only the 13, 17, 18, and 19 methyl branched substrates were desaturated at significant rates. The 2, 5, and 10 methyl branched isomers were virtually inactive (Do and Sprecher, 1975). It remains to be determined whether a single acyl-CoA 5-desaturase can act on such a variety of different substrates. 

Wei Y, Wang D, Pagliassotti MJ. Saturated fatty acid-mediated endoplasmic reticulum stress and apoptosis are augmented by trans-10, cis- 12-conjugated linoleic acid in liver... 

An experimental study reported a CLA level of 1.6 mg/g fat in the liver and 0.6 mg/g fat in the muscle of juvenile yellow perch, even though CLA was absent in then-diet (59). However, Ackman (60) could not detect any CLA in farmed carp, tilapia, and rockfish. It is interesting to note that Chin et al. (10) did not detect the cis-9, trans-11-isomer in CLA from any of their marine samples. Ackman (60), an authority on marine lipids, points out that during chromatographic analysis, the marine fatty acids 18 4n-3 and 18 4n-l elute in the region that CLA isomers occupy. Thus the CLA values recorded for marine products may be due to these 18 4 fatty acids and not CLA itself. With increasing reliance on aquaculture worldwide, the future may see some CLA in marine products if ruminant-derived ingredients are used in their feed. 

Except for eicosanoic acid, the proportions of all fatty acids in egg yolk lipids were significantly (P < 0.01) influenced by the dietary CLA (59). The proportions of myristic, palmitic, and stearic acids, and CLA cis-9,trans- CLA and transit),cis-f2 CLA) in egg yolk lipids were increased by dietary CLA, but those of palmitoleic, oleic, linoleic, and linolenic, arachidonic acids, and DHA were decreased. These changes in fatty acid composition of yolk lipids are similar to those reported by Chamruspollert and Sell (60), although the total CLA concentration observed in the current research when a 5% CLA diet was fed (8.5-8.6%) was less than the 11.2% reported by those authors. The decrease in the concentrations of linoleic and linolenic acids in yolk lipids of hens fed CLA likely reflects the relatively low concentration of these fatty acids in the CLA source compared with soybean oil. Decreases in arachidonic acid and DHA in yolk lipids from hens fed CLA also could be related to the low concentration of dietary linoleic and linolenic acids, which serve as precursors to the formation of arachidonic acid and DHA. Another possibility is that CLA may compete with Unoleic and/or linolenic add for A6-desaturase, the rate-limiting step for the conversion of these fatty acids into arachidonic acid and/or DHA in liver microsomes (48). Feeding CLA increased the concentration of stearic acid in yolk lipids. 

Another compound of interest is dolichol which was first isolated from liver and is now known to be present in many other animal tissues. It is a long chain molecule (n=17-21), its first isoprene residue is saturated and it has 2 trans double bonds. It is found in liver part as the free alcohol and another part esteri-fied with fatty acids. We now know that a small amount is present as the phosphate or pyrophosphate and may have various sugars joined to it. These dolichol derivatives are involved in the glycosylation of proteins. An excellent review on polyprenols has been written by Hemming (1974). 

The concentration of CLA in plasma lipids is determined by bioavailability from the gut, and subsequent partitioning between p-oxidation, incorporation into tissue lipids, secretion from the gut and liver, and turnover within the plasma compartment. There is only limited information available about the metabolic fate of CLA in humans. Using deuterated fatty acid ethyl esters, Emken et al. (2002) showed that the bioavailability of cis-9,tram- CLA and trans- 0,cis- 2 CLA after a bolus was lower than that of oleic acid. However, since the fatty acids were not ingested as TAG any effect of the conjugated double bonds... 

The cod liver oil proved to be the critical component of the diet. Substitution by com oil made the diet nontoxic, and crude linoleic acid was approximately as effective. The eclamptic disease could be prevented by treating the animals with a-tocopherol or lettuce before the toxic diet was given, or by adding these materials to the eclamptogenic diet. Apart from a possible toxic effect of the vitamin D, it is also possible that the oil itself has a toxic effect. It is known that highly unsaturated acids are present which do not have the activity of the essential unsaturated fatty acids, because they have cis-trans and trans-trans configurations instead of the active cis-ds form. Even deficiency of the essential unsaturated fatty acids may be promoted. The crude linoleic acid, which was not quite as active as corn oil, may contain about 50% of the inactive cis-trans configura-tion(s). The vitamin E content of the com oil is probably important also. 

Following the discovery of peroxisomal long chain fatty acid P-oxidation in rat liver and its induction by hypolipidemic drugs, the involved enzymes were characterized mainly by Hashimoto, Osumi and coworkers in liver from induced rats. This resulted in the following picture. After activation, the CoA-esters are desatured by an FAD-dependent acyl-CoA oxidase. The formed 2-trans- noy -Cok is hydrated to a 3-L-hydrox-yacyl-CoA that is subsequently dehydrogenated to a 3-oxoacyl-(ToA. These reactions are... 

A%A-Enoyl-CoA isomerase activity (EC 5.3.3.8) was first demonstrated in isolated rat liver mitochondria by Stoffel and coworkers. The enzyme catalyzes the conversion of both cis and tra 5-3-enoyl-CoA esters to their trans-2 counterparts with the catalytic rate being about ten times higher for cw-enoyl-CoA substrates. Originally, isomerase was regarded as an obligatory enzyme for the metabolism of monounsaturated and polyunsaturated fatty acids with double bonds at odd-numbered carbon atoms, e.g. oleic, linolenic and arachidonic acids. However, according to recent data, isomerase also participates in the P-oxidation of unsaturated fatty acids with double bonds at even-numbered position, since A intermediates arise from double bonds at the A -position via a 2,4-dienoyl-CoA reductase-dependent pathway" (see below). 

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