Lipid unesterified fatty acid

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... 

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... 

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. 

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.

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... 

Unesterified fatty acids within cells are commonly bound by fatty acid-binding proteins (FABPs), which belong to a group of small cytosolic proteins that facilitate the Intracellular movement of many lipids. These proteins contain a hydrophobic pocket lined by p sheets (Figure 18-3). A long-chain fatty acid can fit into this pocket and Interact noncovalently with the surrounding protein. 

Trace amounts of many other proteins are recovered in purified fractions of plasma lipoproteins. Some, like albumin, have plausible functions both at the lipoprotein surface [binding unesterified fatty acids newly generated from lipoprotein triacylglycerol (TG)] and in free solution to ensure osmotic balance between cells and their surroundings. Blood-clotting proteins are present in low amounts in TG-rich lipoproteins, but it is not clear that they play a unique biological role in lipoproteins. Many lipoprotein-associated proteins have no known function in lipid transport. 

The principal lipids of milk are triacylglycerols which may represent up to 98% of the total lipids (Table 3.219). Human milk contains significant quantities of phospholipids, sterols, sterol esters, unesterified fatty acids and monoacylglycerols. In contrast, the proportion of phospholipids in bovine milk is low (Table 3.219). 

The most obvious connection of skin lipids with medical problems has been with acne vulgaris. It is often stated that the severity of acne correlates with the amount of seborrhoea (Cunliffe and Shuster, 1969). Moreover, unesterified fatty acids have been thought to play a role in its pathogenesis since they are both irritant and comedogenic (Stillman et ai, 1975). However, the importance of unesterified fatty acids in the pathogenesis of acne has been doubted by others (e.g. Voss, 1974). 

The composition of skin surface lipids varies over the body but in sebaceous-enriched parts such as the face, scalp and upper trunk about 95% of the lipid is sebum (Greene et al, 1970). The epidermal portion contains mainly cholesterol, cholesterol esters and triacylglycerols. When sebum is freshly formed it consists mainly of triacylglycerols, wax esters and squalene (Table 12.4). Little or no unesterified fatty acid is present at first but this is generated by bacterial lipases. There are large differences in the skin surface... 

The difference between the alcohol and the lipids is probably due to the limited number of pathways which would lead to retention of l C of the labeled ethanol. The greater yield of C02 per mMole acyl carbon from labeled unesterified fatty acids in contrast to... 

The composition of human skin surface lipids varies over the body but in sebaceous gland-enriched areas (such as the face) the secretion, sebum, may represent 95%. When sebum is freshly formed it contains mainly triacylglycerols, wax esters and squalene. However, due to bacterial action, unesterified fatty acids are rapidly released. These acids are both irritant and comedogenic (give rise to black-heads ) and have been implicated in acne vulgaris - an extremely common complaint of puberty. It is often stated that the severity of acne correlates with the amount of seborrhoea and many treatments are designed primarily to remove epidermal lipids from the skin surface. 

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. 

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. 

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. 

Phospholipids and glycosphingolipids are amphipathic lipid constituents of membranes (Chapter 10). They play an essential role in the synthesis of plasma lipoproteins (Chapter 20) and eicosanoids (Chapter 18). They function in transduction of messages from cell surface receptors to second messengers that control cellular processes (Chapter 30) and as surfactants. Cholesterol is mainly of animal origin and is an essential constituent of biomembranes (Chapter 10). In plasma, cholesterol is associated with lipoproteins (Chapter 20). Cholesterol is a precursor of bile acids formed in the liver of steroid hormones secreted by adrenals, gonads, and placenta and 7-dehydrocholesterol of vitamin D formed in the skin. In tissues, cholesterol exists primarily in the unesterified form (e.g., brain and erythrocytes), although appreciable quantities are esterified with fatty acids in liver, skin, adrenal cortex, and plasma lipoproteins. 

The receptor SR-BI differs In two Important respects from the LDL receptor. First, SR-BI clusters on microvilli and in cell-surface lipid rafts (Chapter 5), not In coated pits as does the LDL receptor. Second, SR-BI mediates the transfer of lipids across the membrane, not endoc3rt osIs of entire LDL particles as mediated by the LDL receptor. A multifunctional receptor, SR-BI can mediate the selective uptake from lipoproteins of diverse lipids (e.g., cholesteryl esters, vitamin E) it also functions in the reverse direction to facilitate the export of unesterified cholesterol from cells to bound lipoproteins. SR-BI has a structure similar to that of the fatty acid transporter CD36, and they both belong to the superfamily of scavenger receptors as discussed later, some of these receptors apparently play a role In the onset of atherosclerosis. 

Polyunsaturated fatty acids and especially arachidonic acid are highly susceptible to lipid peroxidation, which leads to the generation of lipid hydroperoxides, which then undergo carbon-carbon bond cleavage giving rise to the formation of short chain, unesterified aldehydes and aldehydes still esterified to the parent lipid, termed core-aldehydes (Esterbauer et al. 1987). Considerable progress has been made in recent years in dissecting the molecular structures of OxPL, which consequently allowed for the experimental use of defined compounds rather than complex lipoproteins and lipid mixtures. 

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