Unesterified fatty acids

In vertebrates, free fatty acids (unesterified fatty acids, with a free carboxylate group) circulate in the blood bound noncovalently to a protein carrier, serum albumin. However, fatty acids are present in blood plasma mostly as carboxylic acid derivatives such as esters or amides. Lacking the charged carboxylate group, these fatty acid derivatives are generally even less soluble in water than are the free fatty acids. 

Dietary triglycerides and esterified cholesterol and phospholipids are broken down in the intestine Uiivugh, respectively, pancreatic lipase, cholesterol ester hydrolase, and phospholipase A2, to form free fatty acids, unesterified cholesterol and lysophospholipids (phospholipids with only one fatty acid group), which are absorbed. 

The LDL receptor pathway assures a constant steady-state level of cellular cholesterol. This is accomplished both by adjusting cellular cholesterol synthesis according to ambient LDL levels and by altering LDL receptor number to limit the amount of LDL getting into cells. Like free fatty acids, unesterified cholesterol can be toxic to cells. The formation of cholesterol esters protects cells from cholesterol toxicity. 

When most lipids circulate in the body, they do so in the form of lipoprotein complexes. Simple, unesterified fatty acids are merely bound to serum albumin and other proteins in blood plasma, but phospholipids, triacylglycerols, cholesterol, and cholesterol esters are all transported in the form of lipoproteins. At various sites in the body, lipoproteins interact with specific receptors and enzymes that transfer or modify their lipid cargoes. It is now customary to classify lipoproteins according to their densities (Table 25.1). The densities are... 

Fatty acid transport proteins (FATPs) are an evolutionary conserved family of integral membrane proteins found at the plasma membrane and on internal membranes. FATPs facilitate the unidirectional uptake and/ or intracellular activation of unesterified long-chain and very long-chain fatty acids (LCFAs) into a variety of lipid-metabolizing cells and tissues. 

Fatty acids occur mainly as esters in natural fats and oils but do occur in the unesterified form as free fatty acids, a transport form found in the plasma. Fatty acids that occur in natural fats are usually straight-chain derivatives containing an even number of carbon atoms. The chain may be saturated (containing no double bonds) or unsaturated (containing one or more double bonds). 

Free fatty acids—also called unesterified (UFA) or non-esterified (NEFA) fatty acids—are fatty acids that are in the unesterified state. In plasma, longer-chain FFA are combined with albumin, and in the cell they are attached to a fatty acid-binding protein, so that in fact they are never really free. Shorter-chain fatty acids are... 

More than 600 different carotenoids from natural sources have been isolated and characterized. Physical properties and natural functions and actions of carotenoids are determined by their chemical properties, and these properties are defined by their molecular structures. Carotenoids consist of 40 carbon atoms (tetraterpenes) with conjugated double bonds. They consist of eight isoprenoid units j oined in such a manner that the arrangement of isoprenoid units is reversed at the center of the molecule so that the two central methyl groups are in a 1,6-position and the remaining nonterminal methyl groups are in a 1,5-position relationship. They can be acyclic or cyclic (mono- or bi-, alicyclic or aryl). Whereas green leaves contain unesterified hydroxy carotenoids, most carotenoids in ripe fruit are esterified with fatty acids. However, those of a few... 

Mercury is known to exert an effect on the synthesis of membrane lipids. Mercuric chloride produces lipid alteration in pig kidney epithelial cells (LLC-PK, cells), with rapid accumulation of unesterified fatty acids (particularly arachidonic acid) and lysophospholipids and loss of cellular phospholipids... 

The naturally occurring fatty acids are carboxylic acids with unbranched hydrocarbon chains of 4-24 carbon atoms. They are present in all organisms as components of fats and membrane lipids, in these compounds, they are esterified with alcohols (glycerol, sphingosine, or cholesterol). However, fatty acids are also found in small amounts in unesterified form. In this case, they are known as free fatty adds (FFAs). As free fatty acids have strongly amphipathic properties (see p. 28), they are usually present in protein-bound forms. 

Their relative blood concentrations are an expression of nutritional balance, providing a view of the metabolic disturbances arising in a patient. In conjunction with the measurement of unesterified fatty acids (UEFA) and glucose, they are useful tools with which to investigate intermediary metabolism in health and disease, particularly in inherited metabolic diseases. 

Table 1.4.14 Data from a patient affected with a long-chain 3-hydroxyacyl enzyme A dehydrogenase defect. UEFA Unesterified fatty acids...

LCAT catalyzes the transfer of a preferentially unesterified fatty acid from the sn-2 position of phosphatidylcholine to the 3/i-hydroxy group of cholesterol, and thereby produces lysophosphatidylcholine and a cholesteryl ester [50]. Depending on the mutation in the LCAT gene, homozygous or compound heterozygous patients present with one of two clinical phenotypes, classical LCAT deficiency or fish-eye disease [58, 85]. Classical LCAT deficiency is caused by a broad spectrum of missense and non-sense mutations that interfere with the synthesis or secretion or affect the catalytic activity of LCAT [10]. Fish-eye disease is caused by a limited number of missense point mutations that alter the surface polarity, and thereby interfere with the binding of the enzyme to apoA-I containing lipoproteins [77]). 

An adult ingests about 60 to 150 g of lipids per day, of which more than n nety percent is normally triacylglycerol (formerly called triglyceride). Uhe remainder of the dietary lipids consists primarily of cholesterol, cholesteryl esters, phospholipids, and unesterified ("free") fatty acids. "The digestion of dietary lipids is summarized in Figure 15.2. 

Fate of fatty acids The free (unesterified) fatty acids move through the cell membrane of the adipocyte, and immediately bind to albumin in the plasma. They are transported to the tis sues, where the fatty acids enter cells, get activated to their CtA derivatives, and are oxidized for energy. [Note Active transport of fatty acids across membranes is mediated by a membrane fatty acid binding protein.] Regardless of their blood levels, plasma free fatty acids cannot be used for fuel by erythrocytes, which have no mitochondria, or by the brain because of the imperme able blood-brain barrier. rr f-... 

The receptors can be recycled, whereas the lipoprotein remnants in the vesicle are transferred to lysosomes and degraded by lysosomal (hydrolytic) enzymes, releasing free cholesterol, amro acids, fatty acids, and phospholipids. These compounds can be reutilized by the cell. [Note Rare autosomal recessive deficiencies in the ability to hydrolyze lysosomal cholesteryl esters (Wolman disease), or to transport unesterified cholesterol out of the lyso some (Niemann-Pick disease, type C) have been identified.]... 

The lipases of milk are apparently inactive in the udder and at the time of milking. Milk always contains relatively large proportions of unesterified fatty acids (Thomas et al. 1955A), but these may be left over from the metabolic pool. 

Bacteria usually lack polyunsaturated fatty acids but often contain branched fatty acids, cyclopropane-containing acids, hydroxy fatty acids, and unesterified fatty acids. Mycobacteria, including the human pathogen Mycobacterium tuberculosis, contain mycolic acids. In these compounds the complex grouping R contains a variety of functional groups including -OH, -OCH3,... 

Unesterified fatty acids are carried in plasma by albumin (chapter 18). The plasma also transports more complex lipids (cholesterol, triacylglycerols) among the various tissues as components of lipoproteins (spherical particles composed of lipids and proteins). Because cholesterol and triacylglyc-erol are insoluble in an aqueous medium such as the plasma, these lipoproteins (which are soluble in plasma) have evolved for the purpose of transporting complex lipids among tissues. In this section we are concerned with the structure and metabolism of these lipoproteins. 

Some cholesterol entering from the diet may be esterified to various fatty acids, although the extent of esterification is variable. For example, egg yolk cholesterol is about 10% esterified (Bitman and Wood, 1980 Tattrie, 1972) cholesterol in meat and poultry is at least 50% esterified (Kritchevsky and Tepper, 1961). Esterified cholesterol entering the intestinal tract is mostly hydrolyzed by pancreatic enzymes, yielding free cholesterol and fatty acids (Howies et al., 1996). Only unesterified cholesterol is available for absorption. 

Figure 22 Dynamics of principal lipid constituents in horse-mackerel during cruising and fatigue. (After Yuneva et al., 1991.) The free fatty-acid level increases in red muscle and liver when the fish swim, and decreases during fatigue. Other constituents decrease under both conditions. TG, triacyl-glycerols PL, phospholipids PC, phosphatidyl choline PE, phosphatidyl ethanolamine FFA, free (unesterified) fatty acids. Black columns, red muscle empty columns, white muscle shaded, liver.

Another possible dietary factor concerns the essential fatty acid content of human and artificial milk. It has been postulated by Sinclair that many modern dietaries are deficient in the essential polyethenoid fatty acids (EFA) and that in consequence there is a rise in unesterified (and more active) vitamin D and in unesterified cholesterol. He has suggested that a part of the etiology of infantile idiopathic hypercalcemia may be attributed to EFA deficiency (S5). He has pointed to the lower content of certain unsaturated fatty acids in cow s milk as compared with human milk as a factor in the development of idiopathic hypercalcemia in artificially fed infants. He considers that dried milk has an even lower content of essential fatty acids than liquid cow s milk and that the longer it is stored the lower does the essential fatty acid content become. On the basis of some observations on rats, he suggests that a dietary deficiency of the essential fatty acids increases susceptibility to the possible toxic effects of vitamin D. The age of the rats, the duration of the essential fatty acid deficient diet, or the dosage of vitamin D is not mentioned, and there would appear to be no other experimental data to support these views. 

Fatty acid methyl esters C. verticillatum total Intestinal content unesterified fatty Intestinal content entire Bile Blood plasma Intestinal wall Liver... 

Partial esters of fatty acids with polyhydroxy compounds of the type CH2OH (CHOH) CH2OH where n = 0-4 are the basis of a useful class of surfactants. The weak hydrophobic properties are provided by the unesterified hydroxyl group, which essentially limits the range to monoesters. In general, monoesters of lauric, palmitic, stearic and oleic... 

The composition and structure of bovine milk fat have been reviewed extensively. There are early reviews by Morrison (1970), Christie (1978, 1995), Jensen and Clark (1988), and Jensen and Newberg (1995) recent articles include a comprehensive review of recent research by Jensen (2002) and two book chapters by Vanhoutte and Huyghebaert (2003), and Zegarska (2003). Bovine milk lipids are similar to the milk lipids of other species as they are largely composed of triacylglycerols however, there are also minor amounts of diacyl-glycerols, monoacylglycerols, free (unesterified) fatty acids, phospholipids and... 

Monoacylglycerols and diacylglycerols may be genuine membrane constituents or may be products of lipolysis. Unesterified fatty acid levels... 

Parks, O.W., Allen, C. 1979. State of unesterified fatty acids in skim-milk. J. Dairy Sci. 62, 1045-1050. 

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