Short-chain fatty adds

Fats and oils are important food constituents. Their nutritional, chemical, and physical properties are influenced by the position of fatty adds, their chain length, and the degree of unsaturation. Usually, lipases are used to obtain modified fats with nutritionally improved properties and they provide high value fats such as cocoa butter that contains palmitic and stearic acids. Commercial lipases are mainly employed in the dairy industry for flavor enhancement in cheese (Mase et al., 2010 Omar et al., 1986), the acceleration of cheese ripening (Fox et al., 1996 Kheadr et al., 2002), the manufacture of cheeselike products, and the Upolysis of butterfat and cream (Purko et al., 1952 Seitz, 1974). Lipases release short-chain fatty acids that develop a tangy flavor and medium chain fatty acids that give a soapy taste to the end product (Sharma et al., 2011). 

Ruminant milk fats contain a high level of butanoic add (C4 0) and other short-chain fatty acids. The method of expressing the results in Table 3.6 (%, w/w) under-represents the proportion of short-chain adds-if expressed as mol %, butanoic acid represents c. 10% of all fatty acids (up to 15% in some samples), i.e. there could be a butyrate residue in c. 30% of all triglyceride molecules. The high concentration of butyric (butanoic) acid in ruminant milk fats arises from the direct incorporation of jS-hydroxybutyrate (which is produced by micro-organisms in the rumen from carbohydrate and transported via the blood to the mammary gland where it is reduced to butanoic acid). Non-ruminant milk fats contain no butanoic or other short-chain adds the low concentrations of butyrate in milk fats of some monkeys and the brown bear require confirmation. 

In mitochondria, there are four fatty acyl CoA dehydrogenase species, each of which has a specificity for either short-, mediurr-long-, or very-long-chain fatty acids. MCAD deficiency, an autos mal, recessive disorder, is one of the most common inborn errors of metabolism, and the most common inborn error of fatty add oxidation, being found in 1 in 12,000 births in the west, and 1 in 40,000 worldwide. It causes a decrease in fatty acid oxidation and severe hypoglycemia (because the tissues cannot obtain full ener getic benefit from fatty acids and, therefore, must now rely on glu cose). Treatment includes a carbohydrate-rich diet. [Note Infants are particularly affected by MCAD deficiency, because they rely for their nourishment on milk, which contains primarily MCADs. 

Inhibition of HDACs is one key mechanism to reactivate the expression of these misregulated genes. The astounding tumor specificity of many HDAC inhibitors relays the potential for many of these new compounds for the treatment of cancer and perhaps other disorders. There are five classes of HDAC inhibitors (reviewed in Refs. 51 and 52) including (i) short-chain fatty adds such as sodium- -butyrate (ii) hydroxyamic acids, such as trichostatin A (TSA), suberoylanilide hydroxamic add (SAHA), m-carboxycinnamic acid bishydroxamic acid (CBHA), azelaic bishydroxamic acid (ABHA), and... 

Figure 19.6 indicates the oxidation of palmitoyl-CoA to myristoyl-CoA with the production of an acetyl-CoA molecule. The myristoyl-CoA molecule can undergo another oxidative cycle, and so on. Note that the /3-hydroxyacyl-CoA dehydrogenase is specific for the l isomer of /3-hydroxyacyl-CoA. Also note that at least three acetyl-CoA dehydrogenases exist, one favoring short-chain fatty acids, another intermediate-length fatty adds, and the third long-chain fatty adds. 

Palmitate can serve as a precursor for both longer and unsaturated fatty adds. Chain elongation takes place in both the endoplasmic reticulum and mitochondria. In the latter, this is a simple reversal of the /3-oxidation reaction sequence, except that the step that would normally require FADH2 requires NADPH instead. This system is designed for the elongation of short-chain acids. There is no activity with palmitate. 

Whether dietary fiber is required for the health of the colonocylcs has not been proven, although evidence suggests such a requirement Absorption of salts and water is a major function of the large intestine. Short-chain fatly adds stimulate the absorption of sodium, chloride, and water in the colon (Hoverstad, 1986). in the absence of short-chain fatty acids, the mucosa of the colon may become inflamed or atrophied. 

Table 4.11 li ts the maximum solubilities of various fatty acids in salt water. Butyric acid, a short-chain fatty acid with 4 carbons, is quite soluble in water and can be dissolved, in the laboratory, to a concentration of about 600 mM. Octanoic add (8 carbons) slightly soluble and can be dissolved to about 20 mM. Fatty adds containing 8 to ID or 12 carbons arc medium-chain fatty adds. Palmitic (16 Carbons), oleic (18 carbons), and longer fatly adds are long-chain fatty acids. The highest concentration attainable for long-chain fatty acids range from 0.1 jiAf to 0.1 mM. 

Carnitine is required for transport of longoxidative metabolism as well as in the formation of ketone bcidies, The concentration of free carnitine in muscle is about 4,0 mmol/kg. The concentration of carnitine bound to long-chain fatty adds (fatty acyl-camitine) is lower, about 0,2 mmol/kg. Short-chain fatty adds, including acetic, are also esterified to carnitine, but the functions of these complexes are not clear. There is some indication that keto forms of BCAAs (BCKAs) can also be esterified to carnitine. These complexes can then be transported into the mitochondria for complete oxidation of the BCKAs, The importance of this mode of BCKA transport is not dear (Takakura et ai., 1997). 

The nature of a fatty add influences its fate. Short- and medium-tdiain fatty adds tend to be oxidised immediately to carbon dioxide, rather than deposited as TGs or phospholipids. The presence of double bonds ("unsaturations") in long-chain fatty adds influences the immediate fate of the add. Some evidence suggests that unsaturated fatty acids, such as 18 2, tend to be oxidized at a slightly faster rate in the hours following a meal than saturated fatty acids, such as 18 0 (Jones et al., 1985, Jones and Schoeller, 1988). More specifically, about 2% of a test meal of 18 0 may be oxidized in the 9 hours toUowing Ingestion, whereas about 10% of a test meal of 18 2 may be oxidized in the same period, The mechanisms that influence the fates of unsahirated and saturated fatty adds are only beginning to be understood. 

A short-chain fatty add thiokinase catalyzes the ATP-dependent conversion of propionic acid to propionyl-CoA. Which cells of the gastrointestinal tract might be expected to have high levels of short-chain thiokinase and of methylmalonyl-CoA mutase. Hint see the section on Dietary Fiber in Chapter 3. 

In the cytosol of the cell, long-chain fatty adds are activated by ATP and coenzyme A, and fatty acyl CoA is formed (Figure 6-12). Short-chain fatty acids are activated in mitochondria. 

Hirayama, F., Ogata, T., Yano, H. et al. Release characteristics of a short-chain fatty add, n-butyric acid, from its (3-cyclodextrin ester conjugate in rat biological media. J. Pharm. Sci. 2000, 89, 1486-1495. 

Wegener, W.S., H.C. Reeves, R. Rabin, and S.J. Ajl. 1968. Alternate pathways of metabolism of short-chain fatty adds. Bacteriol. Rev. 32 1-26. 

In order to be metabolized, long-chain fatty acids must first undergo conjugation to carnitine for transport by the acylcamitine-camitine carrier across the mitochondrial inner membrane [139]. Short-chain fatty acids enter the mitochondria through monocarboxylic acid transporters [139]. Studies were carried out to assess the effects cephaloridine, cephaloglydn and cephalexin on the mitochondrial oxidative metabolism of fatty adds such as butyrate and pahnitate [67]. 

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