Long-chain fatty adds

Amplified photochemical quenching of carbazolyl fluorescence was observed in mixed LB films containing pure CUA and long-chain fatty adds [49,51], A pure CUA was synthesized from 2-nitrobiphenyl and 11-bromoundecanoic add methyl ester as reported previously [49,50]. Two monolayers of mixtures of CUA (fc= 0.02 - 0.50) and PA were deposited on five monolayers of cadmium arachidate at 15°C and 20 mN m 1 at pH 6.3. 

Figure 7.11 Mechanism of transport of long-chain fatty adds across the inner mitochondrial membrane as fatty acyl carnitine. CRT is the abbreviation for carnitine palmitoyl transferase. CPT-I resides on the outer surface of the inner membrane, whereas CPT-II resides on the inner side of the inner membrane of the mitochondria. Transport across the inner membrane is achieved by a carrier protein known as a translocase. FACN - fatty acyl carnitine, CN - carnitine. Despite the name, CRT reacts with long-chain fatty acids other than palmitate. CN is transported out of the mitochondria by the same translocase.

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. 

ATP.NADH, citrate, long-chain fatty adds... 

Reduced storage of bilirubin can be caused by the bilirubin competing with exogenous substances for binding to the Y protein or with long-chain fatty adds for binding to the Z protdn. Thus bilirubin may diffuse back from the hver cell into the blood. 

Carnitine is used mainly for facilitating the transport of long-chain fatty adds into the mitochondria. As shown in Figure4.53, this transport system requires the participation of two different carnitine acyl transferases. One is located on the outside of the mitochondrial membrane, the other on the inner side. Once fatty acyl-camitine is inside the organelle, its carnitine is released. A separate transport system is used to transport this carnitine from the interior of the mitochondrion back to the cytoplasm for reuse. 

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. 

Table 4.11 lists the maximum solubilities of various fatty adds in salt water. Butyric add, 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 acid (8 carbons) is slightly soluble and can be dissolved to about 20 mM. Fatty adds containing 8 to 10 or 12 carbons are medium-chain fatty adds. Palmitic (16 carbons), oleic (18 carbons), and longer fatty adds are long-chain fatty acids. The highest concentration attainable for long-chain fatty adds range from 0.1 jiM to 0.1 mM. 

FIGURE 5.7 One cycle in the oxidation of a long-chain fatty add. 

Several observations can be made. One of the major fatty adds of butter is 14 0. Obviously, this fatty acid was not incorporated into the phospholipids of the membrane. Fatty acids with 14 carbons were essentially absent from the membranes. The food lipids did not contain long-chain fatty adds of 20 or 22 carbons however, the membranes contained substantial amoimts of these acids. For example, about 20% of the fatty add content of the membranes of the com oil-fed rat was 20 4. 

The essential fatty acids are also converted in the body to the 22-carbon fatty acids docosapentaenoic acid (DPA)and docosahexaenoic acid (DHA). DPAis made from linoleic acid DHA is made from linolenic acid.The functions of these 22-carb-on fatty acids are not clear, but they may be important for vision and for other functions of the nervous system. DPA and DHA can be further elongated, in the body, to the "very-long-chain fatty acids." The very-long-chain fatty adds contain 24 to 34 carbons, and occur in the brain, rods of the retina, and in the testes (Sixh et al., 1996). Their functions are not clear. 

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. 

Oil Indian mustard [11] Introduction of very long chain fatty adds by introduction of enzymes (fatty add desaturases and elongases, lysophosphatidic add acyltransferase) involved with their biosynthesis... 

Fig. 4.9. Intracellular transport of long-chain fatty adds into mitodrondria.

Long-chain fatty adds, mono- or di-glycerides... 

Wanders, R.J., van Roermund, C.W., van Wijland, M.J., Schulgens, RB., van den Bosch, H., Schram, A.W. Tagcr, J.M. (1988) Biochem. Biopl s. Res. Commun. 153, 618 24. Direct demonstration that the deficient oxidation of very long chain fatty acids in X-linked adrenoleukodystrophy is due to an impaired ability of peroxisomes to activate very long chain fatty adds. 

The release of H20 from [9,10- H]myristate and/or [9,10- I palmitate has been used extensively for detecting medium- and long-chain fatty add oxidation defects, both in cultured fibroblasts and in fresh lymphocytes. Over the past 10 years we have used both substrates to screen routinely for fatty acid oxidation defects in over 1,200 patients and have identified 113 individuals with specific fatty acid oxidation disorders (Table 1). More recently we have examined the use of a third substrate, [9,10- oleate, to improve discrimination of long-chain defects. ... 

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