Mechanism of fatty acids

Fatty acids are biosynthesized by way of acetyl coenzyme A The following sec tion outlines the mechanism of fatty acid biosynthesis... 

Uptake of LCFAs across the lipid-bilayer of most mammalian cells occurs through both a passive diffusion of LCFAs and a protein-mediated LCFA uptake mechanism. At physiological LCFA concentrations (7.5 nM) the protein-mediated, saturable, substrate-specific, and hormonally regulated mechanism of fatty acids accounts for the majority (>90%) of fatty acid uptake by tissues with high LCFA metabolism and storage such as skeletal muscle, adipose tissue, liver,... 

W3. Wakil, S. J., and Gibson, D. M., Studies on the mechanism of fatty acid synthesis. VIII. The participation of protein bound biotin in the biosynthesis of fatty acids. Biochim. et Biophys. Acta 41, 122-129 (1960). 

Recall that fatty acid chains nearly always contain an even number of carbon atoms (see chapter 17). Investigations into the mechanisms of fatty acid catabolism began around the turn of the century when Fritz Knoop reported experiments that indicated fatty acids were degraded by removal of two carbons at a time. The data indicated that carbon 3 of a fatty acid was oxidized with subsequent cleavage between carbons 2 and 3. 

Sun, M.Y., Wakeham, S.G, and Lee, C. (1997) Rates and mechanisms of fatty acid degradation in oxic and anoxic coastal marine sediments. Geochim. Cosmochim. Acta 61, 341-355. 

The mechanism of fatty acid unsaturation (e.g., stearic acid — oleic acid) utilizes a system similar to that involving cytochrome P-450 (Chapter 17) it is micro-some bound, and it includes a heme-containing protein (cytochrome b5), an FAD-containing reductase, and an iron-sulfur center-containing "desaturase." The electron source is NADH or NADPH. Equation (19.14) summarizes this process ... 

The de novo synthesis of fatty acids in the mammary gland utilizes mainly acetate and some (3-hydroxybutyrate. These precursors arise from the microbial fermentation of cellulose and related materials in the rumen. Once in the mammary gland, acetate is activated to acetyl-CoA. The mechanism of fatty acid synthesis essentially involves the carboxylation of acetyl-CoA to malonyl-CoA, which is then used in a step-wise chain elongation process. This leads to a series of short-chain and medium-chain length fatty acids, which differ by two CH2 groups (e.g., 4 0, 6 0, 8 0, etc.) (Hawke and Taylor, 1995). These are straight-chain, even-numbered carbon fatty acids. However, if a precursor such as propionate, valerate or isobutyrate, rather than acetate, is used, branched-chain or odd-numbered carbon fatty acids are synthesised (Jenkins, 1993 see Chapter 2). 

In 1904, Franz Knoop made a critical contribution to the elucidation of the mechanism of fatty acid oxidation and demonstrated that most of the fatty acids are degraded by oxidation at the p-carbon. p-Oxidation of fatty acids takes place in mitochondria. Fatty acids are activated before they enter into mitochondria for oxidation. 

Figure 2. Schematic oxidation mechanism of fatty acids by Penicillium roqueforti.

Lange LG, Mechanism of fatty acid ethyl ester formation and biological significance. Ann NY Acad Sci 1991 625 802-806. 

Fatty-acid synthesis. The pathway and mechanism of fatty-acid synthesis is depicted in this figure. The fatty-acid synthase is a large enzyme complex which contains a number of enzymic activities and acyl carrier proteins. The synthesis is followed only to the formation of butyryl acyl carrier proteins however this, in fact, is repeated until palmytyl acyl carrier protein is formed by the addition of two carbons at a time. The portion added as acetyl CoA, instead of the malonyl CoAs, is indicated in purple to show that the growing chain is added... 

Lee, D.-S., A. Yamada, H. Sugimoto, I. Matsunaga, H. Ogura, K. Ichihara et al. (2003). Substrate recognition and molecular mechanism of fatty acid hydroxylation by cytochrome P450 from Bacillus subtilis. J. Biol. Chem. 278, 9761-9767. 

MOLECULAR MECHANISMS OF FATTY ACID P-OXIDATION ENZYME CATALYSIS... 

Midecular Mechanisms of Fatty Acid -Oxidation Emyme Catalysis... 

Fig. 2. Hypothetical mechanism of fatty acid cyclooxygenase reactions.

Mechanism of Fatty Acid Synthesis in Adipose Tissue... 

The Mechanisms of Fatty Acid Chain Elongation and Desaturation in Animals... 

Fig, 17.18 The mechanisms of fatty acid synthesis. The boldly printed S refers to the central sulphydryl group of the fatty acid synthetase. The peripheral sulphydryl groups are in normal print. 

Mechanisms of Fatty Acid Nitration Chanical and Cell Synthesis... 

Wojtczak, L., Wie.ckowski, M. R. (1999). The Mechanisms of Fatty Acid-Induced Proton Permeability of the Inner Mitochondrial Membrane. Journal of Bioenergetics and Biomembranes, 57(5), 447-455. doi 10.1023/A 1005444322823... 

Lee DS, Yamada A, Sugimoto H, Matsunaga 1, Ogura H, Ichihara K, Adachi S, Park SY, Shiro Y (2003) Substrate recognition and molecular mechanism of fatty acid hydroxylation by cytochrome P450 imm Bacillus subtilis. Crystallographie, speetroseopie, and mutational studies. J Biol Chem 278 9761-9767... 

Porter, N.A. Mechanism of fatty acid and phospholipid autoxidation. Food Tech. 38(3), 49 (1984). 

The molecular mechanism of fatty acid synthesis can best be understood if the anabolism of fatty acid is first examined in bacteria. The fatty acid synthetase complex of bacteria presents two major advantages it is readily solubilized, and it can be resolved into separate protein components. Three major stages of fatty acid synthesis can be described. First, acetyl-CoA reacts with an SH protein to yield bound acetyl derivatives and free CoA. This reaction is catalyzed by a fatty acid transacylase. Second, the acetyl 5 -protein... 

Coon, M.J., Autor, A.P., Boyer, R.F., Lode, E.T., Strobel, H.W. On the mechanism of fatty acid, hydrocarbon, and drug hydroxylation in liver microsomal and bacterial enzyme systems. In Oxidases and related redox systems, vol. 2, p. 529-553. Baltimore, Maryland University Park Press 1973... 

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