Fatty acid synthase regulation

Bennett MK, Lopez JM, Sanchez HB, Osborne TF. Sterol regulation of fatty acid synthase promoter. Coordinate feedback regulation of two major lipid pathways. J Biol Chem 1995 270 25578-25583. 

Before closing we should point out that, over an extended period, dietary conditions can alter the levels of enzymes involved in fatty acid metabolism. For example, the concentrations of fatty acid synthase and acetyl-CoA carboxylase in rat liver are reduced four- to fivefold after fasting. When a rat is fed a fat-free diet, the concentration of fatty acid synthase is 14-fold higher than in a rat maintained on standard rat chow diet. Current evidence indicates that the levels of these enzymes are governed by the rate of enzyme synthesis, not degradation. It appears that synthesis of the enzyme, in turn, is controlled by the rate of transcription of DNA into mRNA. A question of current interest is how this transcription of DNA is regulated. 

Another major lipogenic enzyme, fatty acid synthase, is also regulated in the liver by nutritional status, insulin, glucagon and T3. Wilson et al. [78] have found that stimulation of fatty acid synthase requires both thyroid hormones and insulin (40-fold stimulation), whereas T3 or insulin alone had much smaller effects (2.5.-fold). Experiments performed in the presence or the absence of puromycin suggest that a common T3-induced peptide intermediate regulates the level of both fatty acid synthase and malic enzyme mRNAs. 

Goodridge AG. Regulation of the gene for fatty acid synthase. Fed Proc 45 2399-2405, 1986. 

Fatty acid synthase is transcriptionally regulated by upstream stimulatory factor and sterol regulatory element binding protein Ic (SREBP-lc), in response to feeding/insulin. 

Long-term control is mediated by changes in the rates of synthesis and degradation of the enzymes participating in fatty acid synthesis. Animals that have fasted and are then fed high-carbohydrate, low-fat diets show marked increases in their amounts of acetyl CoA carboxylase and fatty acid synthase within a few days. This type of regulation is known as... 

C. F. Semenkovich. 1997. Regulation of fatty acid synthase (FAS) Prog. Lipid Res. 36 43-53. (PubMed)... 

Regulation of NADl H Production Fatty Acid Synthase Reapiiatory Quotient Data from Human Studies... 

H.S. Sul and D. Wang, Nutritional and hormonal regulation of enzymes in fat synthesis Studies on fatty acid synthase and mitochondrial glycerol-3-phosphate acyltransferase gene transcription, Annu. Rev. Nutr., 1998, 18, 331-351. 

Regulation of metabolic processes can be accomplished by other methods. One is the use of a multienzyme complex (e.g., pyruvate dehydrogenase complex or fatty acid synthase complex) in which various enzymes are organized such that the product of one becomes the substrate for an adjacent enzyme. A single polypeptide chain may contain multiple catalytic centers that carry out a sequence of transformations (e.g., the mammalian fatty acid synthase see Chapter 18). Such multifunctional polypeptides increase catalytic efficiency by abolishing the accumulation of free intermediates and by maintaining a stoichiometry of 1 1 between catalytic centers. 

Wolf, G. 1996, Nutritional and hormonal regulation of fatty acid synthase. Nutr. Rev. 54 122-123. 

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