Synthesis of fatty acids

Fatty acid synthesis provides an organism with a means of storing energy in the form of an organic 

Fatty acid degradation involves a reverse Claisen 

Therefore, we could consider using the Claisen reaction in fatty acid synthesis. 

However, a more favourable pathway is used, employing a more reactive nucleophile. Rather than using the enolate anion derived from acetyl-CoA, nature uses the enolate anion derived from malonyl-CoA. Malonyl-CoA is obtained from acetyl-CoA by means of an enzymic carboxylation reaction, incorporating CO2 (usually from the soluble form bicarbonate). Now CO2 is a particularly unreactive material, so this reaction requires the input of energy (from ATP) and the presence of a suitable coenzyme, biotin, as the carrier of CO2 (see Section 15.9). The 

The Claisen reaction can now proceed smoothly, but nature introduces another little twist. The carboxyl group introduced into malonyl-CoA is simultaneously lost by a decarboxylation reaction during the Claisen condensation. Accordingly, we now see that the carboxylation step helps to activate the a-carbon and facilitate Claisen condensation, and the carboxyl is immediately removed on completion of this task. An alternative rationalization is that decarboxylation of the malonyl ester is used to generate the acetyl enolate anion without any requirement for a strong base (see Box 10.17). 

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Rittenberg and Bloch showed in the late 1940s that acetate units are the building blocks of fatty acids. Their work, together with the discovery by Salih Wakil that bicarbonate is required for fatty acid biosynthesis, eventually made clear that this pathway involves synthesis of malonyl-CoA. The carboxylation of acetyl-CoA to form malonyl-CoA is essentially irreversible and is the committed step in the synthesis of fatty acids (Figure 25.2). The reaction is catalyzed by acetyl-CoA carboxylase, which contains a biotin prosthetic group. This carboxylase is the only enzyme of fatty acid synthesis in animals that is not part of the multienzyme complex called fatty acid synthase. 

Cyanobacteria, prokaryotic algae that perform oxygenic photosynthesis, respond to a decrease in ambient growth temperature by desaturating the fatty acids of membrane lipids to compensate for the decrease in the molecular motion of the membrane lipids at low temperatures. During low-temperature acclimation of cyanobacterial cells, the desaturation of fatty acids occurs without de novo synthesis of fatty acids [110, 111]. All known cyanobacterial desaturases are intrinsic membrane proteins that act on acyl-Hpid substrates. 

The pentose phosphate pathway is an alternative route for the metabolism of glucose. It does not generate ATP but has two major functions (1) The formation of NADPH for synthesis of fatty acids and steroids and (2) the synthesis of ribose for nucleotide and nucleic acid formation. Glucose, fructose, and galactose are the main hexoses absorbed from the gastrointestinal tract, derived principally from dietary starch, sucrose, and lactose, respectively. Fructose and galactose are converted to glucose, mainly in the liver. 

THE MAIN PATHWAY FOR DE NOVO SYNTHESIS OF FATTY ACIDS (LIPOGENESIS) OCCURS IN THE CYTOSOL... 

Domino reactions are not a new invention - indeed, Nature has been using this approach for billions of years However, in almost of Nature s processes different enzymes are used to catalyze the different steps, one of the most prominent examples being the synthesis of fatty acids using a multi-enzyme complex starting from acetic acid derivatives. 

Fatty acid synthesis Synthesis of fatty acid esters for membranes CoA... 

O. Morin, in Recent Developments in the Synthesis of Fatty Acid Derivatives,... 

Lynen s work on the breakdown and synthesis of fatty acids was recognized by the award of a Nobel prize in 1964. 

Examples of such intra cellular membrane transport mechanisms include the transfer of pyruvate, the symport (exchange) mechanism of ADP and ATP and the malate-oxaloacetate shuttle, all of which operate across the mitochondrial membranes. Compartmentalization also allows the physical separation of metabolically opposed pathways. For example, in eukaryotes, the synthesis of fatty acids (anabolic) occurs in the cytosol whilst [3 oxidation (catabolic) occurs within the mitochondria. 

In the bacterium Penicillium chrysogenum the genomic PPTase is similar to others. When the gene was knocked out, the bacteria needed lysine to survive and no longer produced penicillin or pigmentation. However the bacterium still completed the syntheses of roquefortine, another mycotoxin, and fatty acids. This work suggests that the pptase gene is not needed for the synthesis of fatty acids and roquefortine in this species of bacteria. 

Synthesis of fatty acid and thence triacylglycerol, via the fatty acid synthesis and the esterification pathways (Chapter 11). 

The synthesis of fatty acids in humans takes place in the liver and adipose tissue. The rates of synthesis are normally relatively low in adults in developed countries, probably because the normal diet contains such a high proportion of fat which reduces the activities of enzymes involved in fatty acid synthesis by decreasing expression... 

CH 11 SYNTHESIS OF FATTY ACIDS, TRIACYLGLYCEROL, PHOSPHOLIPIDS AND FATTY MESSENGERS... 

The synthesis of fatty acids involves an ordered sequence of condensations (to build up the chain length), reductions (to convert a carbonyl to a methylene group), dehydrations and a further reduction reaction. (A simplified description of condensation and reduction reactions is presented in Figme 11.4.)... 

Synthesis of fatty acids and their incorporation into triacylglycerols are stimulated during this time of energy excess. 

Nagao, A. and Kite, M. (1990) Lipase-catalyzed synthesis of fatty acid esters useful in the food industry. Biocatalysis, 3, 295-305. 

Ester synthesis of fatty acid ethyl ester. The lipase-catalyzed esterification of fatty acid and alcohol is well-known. It was also favorable for the esterification of poly unsaturated fatty acids under mild conditions with the enzyme. However, the activity of native lipase is lower in polar organic solvents, i.e. ethanol and methanol. The synthesis of Ae fatty acid ethyl ester was carried out in ethanol using the palmitic acid-modified lipase. As shown in Figure 7, the reactivity of the modified lipase in this system was much higher than that of the unmoditied lipase. 

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