Fatty acid synthesis, specific

Treating mice with 23 led to the inhibition of atherosclerotic progression, whereas macrophage-specific knockout of LXR exacerbates atherosclerosis [111]. In vivo activation of LXR leads to increased fatty acid synthesis, accumulation of TG and the development of hepatic steatosis [109]. Successful LXR agonists will show desirable HDL elevation without these side effects [112]. 

Fatty acid synthesis is catalysed in animals by the enzyme fatty acid synthase, which is a multifunctional protein containing all of the catalytic activities required. Bearing in mind the necessity to provide a specific binding site for the various substrates involved, and then the fairly complex sequence of reactions carried out, it raises the question of just how it is possible for this process to be achieved at the enzymic level. Nature has devised an elaborate but satisfyingly simple answer to this problem. 

The endoplasmic reticulum is composed of a convoluted network of channels and so has a large surface area. Apart from cytochromes P-450, the endoplasmic reticulum has many enzymes and functions, besides the metabolism of foreign compounds. These include the synthesis of proteins and triglycerides and other aspects of lipid metabolism and fatty acid metabolism. Specific enzymes present on the endoplasmic reticulum include cholesterol esterase, azo reductase, glucuronosyl transferase, NADPH cytochromes P-450 reductase and NADH cytochrome b5 reductase and cytochrome b5. A FAD-containing monooxygenase is also found in the endoplasmic reticulum, and this is discussed later in this chapter. 

Libertini, L. J. and Smith S. 1978. Purification and properties of thioesterase from lactating rat mammary gland which modifies the product specificity of fatty acid synthesis. J. Biol. Chem. 253, 1398. 

Before discussing the specific aspects of regulation of fatty acid metabolism, let us review the main steps in fatty acid synthesis and degradation. Figure 18.18 illustrates these processes in a way that emphasizes the parallels and differences. In both cases, two-carbon units are involved. However, different enzymes and coenzymes are utilized in the biosynthetic and degradative processes. Moreover, the processes take place in different compartments of the cell. The differences in the location of the two processes and in the... 

For some time, the effects of and responses to vitamin E have been interpreted in terms of an antioxidant mechanism of action. However, several observations have raised the question as to whether other mechanisms could be involved. For example, the effects of selenium and vitamin E on growth and polyunsaturated fatty acid synthesis in cultured mouse fibroblasts could not be reproduced by artificial antioxidants [198, 199]. The specific requirement of (+ )-a-toco-pherol for the phenotypic differentiation of the rotifer [200] may not be through an antioxidant mechanism. The effects of vitamin E on differentiation of neuroblastoma cells [201] and metamorphosis of various species [202] are likely to be due to a growth-factor-like action. A study on the interaction... 

G D Agnolo, IS Rosenfeld, J Awaya, S Omura, PR Vagelos. Inhibition of fatty acid synthesis by the antibiotic cerulenin specific inactivation of P-ketoacyl-acyl carrier protein synthase. Biochem Biophys Acta 236 155-166, 1973. 

The three hormones that regulate pheromone production in insects are shown in Figure 1.1. PBAN alters enzyme activity through second messengers at one or more steps during or subsequent to fatty acid synthesis during pheromone production (Rafaeli and Jurenka, Chapter 5). In contrast, 20-hydroxyecdysone and JH induce or repress the synthesis of specific enzymes at the transcription level (Tittiger, Chapter 7 Blomquist, Chapter 9). 

Suh et al. (1999) studied the isoforms of acyl carrier protein involved in seed-specific fatty acid synthesis in coriander seed, ft produces unusual monoenoic fatty acids which constitute over 80% of the total fatty acids of the seed oil. The initial step in the formation of these fatty acids is the desaturation of palmitoyl-ACP (acyl carrier protein) at the DELTA4 or DELTA6 positions to produce DELTA4-hexadecenoic acid (16 1DELTA4) or DELTA6-hexadecenoic acid (16 1DELTA6), respectively. 

Suh, M.C., Schultz, D.J. and Ohlrogge, J.B. (1 999) Isoforms of acyl carrier protein involved in seed specific fatty acid synthesis. Plant Journal 1 7(6), 679-688. 

Identiflcation/quantiflcation of a select group of metabolites, generally part of a specific pathway such as glycolysis or fatty acid synthesis. See Dunn, W.B. and Ellis, D.I., Metabolomics current analytical platforms and methodologies, Trends Anal. Chem. 24, 285-294, 2005. 

Figure 1 Fatty acid synthesis in mammals. Gene encoding enzymes are shown in italics and are based on current evidence for substrate specificities. (A) De novo fatty acid synthesis. (B) Synthesis of the highly unsaturated fatty acids AA, EPA, and DHA from Cl 8 2 oo3 and Cl 8 3 m3 obtained from the diet. Details are found within the text.

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