Fatty acids synthesis and degradation

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... 

The anabolic hormone insulin has the opposite effect to glucagon and epinephrine. It stimulates the formation of triacylglycerols through decreasing the level of cAMP, which promotes the dephosphorylation and inactivation of hormone-sensitive lipase (Fig. 5). Insulin also stimulates the dephosphorylation of acetyl CoA carboxylase, thereby activating fatty acid synthesis (see Topic K3). Thus fatty acid synthesis and degradation are coordinately controlled so as to prevent a futile cycle. 

Fatty acid synthesis and degradation. Fatty acids are synthesized in the cytosol by the addition of two-carbon units to a growing chain on an acyl carrier protein. Malonyl CoA, the activated intermediate, is formed by the carboxylation of acetyl CoA. Acetyl groups are carried from mitochondria to the cytosol as citrate by the citrate-malate shuttle. In the cytosol, citrate is cleaved to yield acetyl CoA. In addition to transporting acetyl CoA, citrate in the cytosol stimulates acetyl CoA carboxylase, the enzyme catalyzing the committed step. When ATP and acetyl CoA are abundant, the level of citrate increases, which accelerates the rate of fatty acid synthesis (Figure 30.8). 

Fatty acid synthesis and degradation are reciprocally regulated so tliat both are... 

Tie reactions constitute a metabolic motif that we will see again in fatty acid synthesis and degradation as well as in the degradation of some amino acids. A methylene group (CH2) is converted into a carbonyl group (C=0) in three steps an oxidation, a hydration, and a second oxidation reaction, Oxaloacetate is thereby regenerated for another round of the cycle, and more energy is extracted in the form of FADH and NADH. 

Fatty acid synthesis and degradation are reciprocally regulated so that both are not simultaneously active. Acetyl CoA carboxylase, the essential control site, is phosphorylated and inactivated by AMP-dependent kinase. The phosphorylation is reversed by a protein phosphatase. Citrate, which signals an abundance of building blocks and energy, partly reverses the inhibition by phosphorylation. Carboxylase activity is stimulated by insulin and inhibited by glucagon and epinephrine. In times of plenty, fatty acyl CoAs do not enter the mitochondrial matrix, because malonyl CoA inhibits carnitine acyl transferase I. 

The addition of water to carbon-carbon double bonds is very common to biology, and a large variety of enzymes from different sources representing almost a hundred different hydro-lyase types have been characterized biochemically. Hydro-lyases are for instance involved in the metabolism of a variety of carbohydrates and play a prominent role in fatty acid synthesis and degradation as well. Despite the abundant presence of hydro-lyases in nature, however, applications of these enzymes in organic chemical synthesis are not as widespread. This is mainly due to the limited availability of these enzymes and the fact that many of the enzymes cannot easily be stably maintained during catalysis. 

Transcriptional regulation of the genes of fatty acid synthesis and degradation... 

Discuss the different modes of regulation of acetyl CoA carboxylase. Explain the reciprocal control of fatty acid synthesis and degradation through global and local regulation and dietary composition. 

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