Degradation of fatty acids

These changes in animal fatty acid synthetase (FAS) levels have now been studied at the subcellular level. FAS mRNA has been isolated from different tissues after various hormonal or dietary manipulations and translated in vitro. Recombinant plasmids have been used to ascertain the size of FAS mRNA and also the amounts of this mRNA in tissues. By these means it has been shown that differences in FAS activity are caused by changes in enzyme levels rather than its intrinsic activity. These alterations are themselves changed by the balance of enzyme synthesis and degradation, mediated by the quantity of FAS mRNA present in the cell. 

A common way in which the rate of a particular metabolic reaction can be controlled is through the supply of substrate. In the case of animal fatty acid synthetase, this regulation has been examined with regard to NADPH. However, it appears that NADPH production is adjusted to cope with the altering demands of fatty acid synthesis rather than the other way around. In contrast, supply of malonyl-CoA by acetyl-CoA carboxylase activity (section 3.2.7(a)) is considered to be a major factor regulating overall fatty acid (and lipid) formation under many conditions. 

The above mechanisms probably apply also to organisms other than animals. Thus, in developing seeds, where there is a spectacular rise in fat accumulation during a particular stage of maturation, the increase in fatty 

Dietary changes that result in the induction of synthesis of fatty acid synthetase produce similar rises in activity of A9 desaturase but have little effect on A4, A5 or A6 desaturases. Several hormones have been reported to influence desaturase activity, notably insulin. In the rat, made diabetic by poisoning the pancreas with streptozotocin, liver A9 desaturase activity is low and can be restored by administration of insulin. However, dietary fructose, glycerol or saturated fatty acids can also restore enzyme activity, so that the role of insulin may be indirect. Little further progress can be made until purified desaturases are available so that short- and long-term regulation can be studied directly. 

The main pathways of fatty acid breakdown involve oxidation at various points on the acyl chain or lipoxidation at certain double bonds of specific unsaturated fatty acids. The main forms of oxidation are termed a-, and (0-. They are named depending on which carbon of the acyl chain is attacked  

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Separation of Fatty Acids. Tall oil is a by-product of the pulp and paper manufacturiag process and contains a spectmm of fatty acids, such as palmitic, stearic, oleic, and linoleic acids, and rosia acids, such as abietic acid. The conventional refining process to recover these fatty acids iavolves iatensive distillation under vacuum. This process does not yield high purity fatty acids, and moreover, a significant degradation of fatty acids occurs because of the high process temperatures. These fatty and rosia acids can be separated usiag a UOP Sorbex process (93—99) (Tables 8 and 9). 

Cysteine [52-90 ] is a thiol-bearing amino acid which is readily isolated from the hydrolysis of protein. There ate only small amounts of cysteine and its disulfide, cystine, in living tissue (7). Glutathione [70-18-8] contains a mercaptomethyl group, HSCH2, and is a commonly found tripeptide in plants and animals. Coenzyme A [85-61-0] is another naturally occurring thiol that plays a central role in the synthesis and degradation of fatty acids. 

The oxidation/reduction reactions that require one of the nicotinamide coenzymes are everywhere in metabolism in the glycolytic pathway, the citric acid cycle, the synthesis and degradation of fatty acids, the synthesis of steroids, and so on. Certain of... 

The most important process in the degradation of fatty acids is p-oxidation—a metabolic pathway in the mitochondrial matrix (see p. 164). initially, the fatty acids in the cytoplasm are activated by binding to coenzyme A into acyl CoA [3]. Then, with the help of a transport system (the carnitine shuttle [4] see p. 164), the activated fatty acids enter the mitochondrial matrix, where they are broken down into acetyl CoA. The resulting acetyl residues can be oxidized to CO2 in the tricarboxylic acid cycle, producing reduced... 

Most fatty acids are saturated and even-numbered. They are broken down via p-oxidation (see p.l64). In addition, there are special pathways involving degradation of unsaturated fatty acids (A), degradation of fatty acids with an odd number of C atoms (B), a and ro oxidation of fatty acids, and degradation in peroxisomes. 

Fig. 6 Hock cleavage degradation of fatty acids. Reproduced from [33] by permission of Springer...

Scheme 7.1 Enzymatic degradation of fatty acids by the j -oxidation cycle and formation of various types of aroma compounds in fruits and vegetables...

The flavour of distillates from apple and pear is characterised by typical aroma compounds from these fruits formed by enzymatic degradation of fatty acids to C6-fragments like hexanol, trans-2-hexenol, as well as ethyl esters and acetates of hexanoic acid. In distillates of pears, especially of the variety Bartlett pear, the characteristic pear flavour is mainly dominated by the ethyl and methyl esters of frans-2-czs-4-decadienoic acid and trans-2-trans-A-decadienoic acid [27-29], The biogenesis of these monounsaturated, diunsaturated, and triunsaturated esters may be explained by -oxidation of unsaturated linoleic and linolenic acid in the fruits. The sesquiterpene compound a-farnesene, which is formed during postharvest ripening and storage of Bartlett pears [28], shows that quality and intensity of distilled pear spirits is mainly influenced by the quality and degree of ripeness of the fruits. 

A, freeing carnitine to return to the intermembrane space through the same transporter. Acyltransferase I is inhibited by malonyl-CoA, the first intermediate in fatty acid synthesis (see Fig. 21-1). This inhibition prevents the simultaneous synthesis and degradation of fatty acids... 

A very well known dairy product is Roquefort cheese, its flavour is generated by mould action. This so called Blue cheese flavour is attributed to methyl ketones and is formed by the degradation of fatty acids by Penicillium roquefortii. The production of these bioflavours has also been investigated by our group [12,13] and will not be further discussed here. 

The reverse of the above reaction is a key step in the oxidative degradation of fatty acids. This reverse Claisen condensation (catalyzed by thiolase) involves the cleavage of a carbon-carbon bond of a /3-keto ester of coenzyme A by another molecule of coenzyme A to give a new acyl derivative (RCO—SCoA) and ethanoyl (acetyl) derivative (CH3CO—SCoA) ... 

Exercise 20-25 A first step in unravelling the mechanism of the metabolism of fatty acids was made in 1904 by F. Knoop, who found that dogs metabolized 4-phenyl-butanoic acid to phenylethanoic acid and 3-phenylpropionic acid to benzoic acid. What does this pattern of results indicate about the mechanism of degradation of fatty acids Give your reasoning. 

What effect would the following have on the control of the citric acid cycle (a) a sudden influx of acetyl-CoA from the degradation of fatty acids, and... 

Synthesis and degradation of fatty acids. Both synthesis and degradation of fatty acids occur by multistep pathways involving totally different enzymes located in different parts of the cell. Both pathways are similar in that two carbon atoms are either added (in synthesis) or deleted (in degradation) in each round of a repetitious, cyclical process. 

The degradation of fatty acids also involves a repetitious process yielding a two-carbon unit (acetyl-CoA) in every cycle. This acetyl-CoA can be fed into the TCA cycle, or, alternatively, it can be used to make ketone bodies. 

Elaborate controls prevent synthesis and degradation of fatty acids from occurring simultaneously. 

Comparison between synthesis and degradation of fatty acids in the liver. Both processes involve two carbons at a time and very similar intermediates, even though they go in opposite directions. CoA is also heavily involved in both processes. Here the similarities end. The enzymes used in the two processes are totally different, and the coenzymes are also different. In the degradative direction FAD and NAD+ are used, whereas in the synthetic direction the coenzyme NADPH is used. Degradation occurs in the mitochondrial matrix, and synthesis occurs in the cytosol. 

The degradation of fatty acids occurs by an oxidation process in the mitochondria. The breakdown of the 16-carbon saturated fatty acid, palmitate, occurs in blocks of two carbon atoms by a cyclical process. The active substrate is the acyl-CoA derivative of the fatty acid. Each cycle involves four discrete enzymatic steps. In the process of oxidation the energy is sequestered in the form of reduced coenzymes of FAD and NAD+. These reduced coenzymes lead to ATP production through the respiratory chain. The oxidation of fatty acids yields more energy per carbon than the oxidation of glucose because saturated fatty acids are in the fully reduced state. 

Kawaguchi A and Iwamoto-Kihara A (1999) Biosynthesis and degradation of fatty acids. Comprehensive Natural Products Chemistry, Vol 1. Elsevier, Amsterdam, pp 23-59. 

The oxidative phosphorylation system contains over 80 polypeptides. Only 13 of them are encoded by mtDNA, which is contained within mitochondria, and all the other proteins that reside in the mitochondrion are nuclear gene products. Mitochondria depend on nuclear genes for the synthesis and assembly of the enzymes for mtDNA replication, transcription, translation, and repair (Tl). The proteins involved in heme synthesis, substrate oxidation by TCA cycle, degradation of fatty acids by /i-oxidalion, part of the urea cycle, and regulation of apoptosis that occurs in mitochondria are all made by the genes in nuclear DNA. 

FIGURE 7.6 Short-chain aldehydes and alcohols produced from the degradation of fatty acids in grapes via the lipoxygenase (LOX)/hydroperoxide lyase (HPL) pathway during the prefermentative stages of vinification (adapted from Camara, 2004). 

Oxidation The individual reactions involved in the degradation of fatty acids by (3-... 

Other investigators (7-9) have identified a large number of carbonyls from heated fat. The remaining meat aroma components derived by heating lipids are esters, lactones, alkan-2-ones (methyl ketones), benzenoids and other alkylfurans. Several investigators have analyzed volatile compounds formed during thermal degradation of fatty acids (10-12). 

Acetyl-CoA is produced from fatty acids, proteins, and carbohydrates and is a central and major compound in intermediary metabolism. The mechanism of its formation from the degradation of fatty acids and proteins is discussed in Chaps. 13 and 15, respectively here, the means whereby carbohydrates form this most important molecule will be presented. The glycolytic pathway can yield pyruvate from all degradable sugars, and this can be converted to acetyl-CoA. Pyruvate enters the mitochondrial matrix and is the substrate for the multienzyme complex pyruvate dehydrogenase. 

Figure 22.8. Reaction Sequence for the Degradation of Fatty Acids. Fatty acids are degraded by the repetition of a...

Figure 22.18. Initiation of Peroxisomal Fatty Acid Degradation. The first dehydration in the degradation of fatty acids in peroxisomes requires a flavoprotein dehydrogenase that transfers electrons to O2 to yield H2O2.

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