Fatty acids metabolic regulation

The ability of an enzyme to respond to concentrations of metabolites other than its substrate and product adds a new dimension to metabolic regulation. It allows the end product of the metabolic pathway to bring about feedback inhibition on earlier steps (Yates and Pardee, 1956). Such feedback control may be exerted by a metabolite several steps removed in a pathway or by metabolites from a different pathway which share a common intermediate with the first pathway. This regul-ability in strategically located enzymes can have profound effects on cellular metabolism. It allows certain key intermediates in one pathway to act as switches for another pathway for example, citric acid can act as the switch for fatty acid metabolism. Regulation by central intermediates—e.g., adenine and pyridine nucleotides—may in fact determine the resultant direction of metabolism as anabolic or catabolic, depending on the energy reserves or redox state of the cell (see metabolite ratios below). 

Substrates change in the setting of heart failure as the heart utilizes less fatty acid metabolism and relies more on carbohydrates [29]. Perhaps by shifting cell use back to fatty acids or optimizing the use of carbohydrates, cardiac function can be improved. The attempt to up-regulate fatty acid... 

Features an important new section on glyceroneogenesis and the triacylglycerol cycle between adipose tissue and liver, including their roles in fatty acid metabolism (especially during starvation) and the emergence of thiazolidinediones as regulators of glyceroneogenesis in the treatment of type II diabetes... 

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... 

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. 

Bremer J, Osmundensen H (1984) In Numa S (ed), Fatty acid metabolism and its regulation. Elsevier, Amsterdam, pp 113-147... 

Stakkestad, J.A., Bremer, J. (1983). The outer carnitine palmitoyltransferase and regulation of fatty acid metabolism in rat liver in different thyroid states. Biochim. Biophys. Acta 750 244-52. 

Yoshikawa T, Ide T, Shimano H, Yahagi N, Amemiya-Kudo M, Matsuzaka T, Yatoh S, Kitamine T, Okazaki H, Tamura Y, et al. Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. I. PPARs suppress sterol regulatory element binding protein-Ic promoter through inhibition of LXR signaling. Mol. Endocrinol. 2003 17 1240-1254. 

Numa, S. Ed. Fatty Acid Metabolism and Its Regulation, Elsevier Amsterdam, 1984. 

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