Metabolic fatty acid degradation

By contrast, acetyl CoA does not have anaplerotic effects in animal metabolism. Its carbon skeleton is completely oxidized to CO2 and is therefore no longer available for biosynthesis. Since fatty acid degradation only supplies acetyl CoA, animals are unable to convert fatty acids into glucose. During periods of hunger, it is therefore not the fat reserves that are initially drawn on, but proteins. In contrast to fatty acids, the amino acids released are able to maintain the blood glucose level (see p. 308). 

In eukaryotes, the cytoplasm, representing slightly more than 50% of the cell volume, is the most important cellular compartment. It is the central reaction space of the cell. This is where many important pathways of the intermediary metabolism take place—e.g., glycolysis, the pentose phosphate pathway, the majority of gluconeogenesis, and fatty acid synthesis. Protein biosynthesis (translation see p. 250) also takes place in the cytoplasm. By contrast, fatty acid degradation, the tricarboxylic acid cycle, and oxidative phosphorylation are located in the mitochondria (see p. 210). 

Compartmentation. Glycolysis takes place in the cytoplasm, whereas fatty acid degradation takes place in mitochondria. What metabolic pathways depend on the interplay of reactions that take place in both compartments ... 

Various tiny structures, so-called organelles, are embedded in the cytoplasm where they make numerous cell functions possible, (s. fig. 2.9) (s. tab. 2.1) The enzyme-rich mitochondria have an outer and an inner membrane, with the latter forming creases (cristae). The outer membrane is relatively permeable for small molecules. However, the inner membrane (which surrounds the matrix) must use specific transport proteins to enable protons, calcium, phosphate and so on to pass. Energy-rich substrates are transformed into ATP in the mitochondria. The enzymes which are responsible for fatty-acid degradation and the citric-acid cycle can be found in the matrix. The inner membrane also contains the enzymes of the so-called respiratory cycle. An enormous number of energy-providing reactions and metabolic processes take effect at this site. They have a round-to-oval shape with a diameter of about 1 im. There are 1,400-2,200 mitochondria per liver cell (18-22% of the liver cell volume). They generally lie in... 

Many aroma compounds in fruits and plant materials are derived from lipid metabolism. Fatty acid biosynthesis and degradation and their connections with glycolysis, gluconeogenesis, TCA cycle, glyoxylate cycle and terpene metabolism have been described by Lynen (2) and Stumpf ( ). During fatty acid biosynthesis in the cytoplasm acetyl-CoA is transformed into malonyl-CoA. The de novo synthesis of palmitic acid by palmitoyl-ACP synthetase involves the sequential addition of C2-units by a series of reactions which have been well characterized. Palmitoyl-ACP is transformed into stearoyl-ACP and oleoyl-CoA in chloroplasts and plastides. During B-oxi-dation in mitochondria and microsomes the fatty acids are bound to CoASH. The B-oxidation pathway shows a similar reaction sequence compared to that of de novo synthesis. B-Oxidation and de novo synthesis possess differences in activation, coenzymes, enzymes and the intermediates (SM+)-3-hydroxyacyl-S-CoA (B-oxidation) and (R)-(-)-3-hydroxyacyl-ACP (de novo synthesis). The key enzyme for de novo synthesis (acetyl-CoA carboxylase) is inhibited by palmitoyl-S-CoA and plays an important role in fatty acid metabolism. 

For the majority of obese humans, who produce leptin, perhaps a genetic defect exists in the leptin receptor. Or perhaps the genetics of obesity in humans is more complex than in mice. Clearly lipid metabolism in animals is a complex process and is not yet fully understood. The discovery of the leptin gene, and the hormone it produces, is just one part of the story. In this chapter we will study other aspects of Upid metaboUsm the pathways for fatty acid degradation and biosynthesis and the processes by which dietary lipids are digested and excess Upids are stored. 

In this chapter we attempted to review the transcriptional regulation of fatty acid metabolism in the liver. Many transcription factors are involved in this process. We chose to focus on PPARa and SREBP-lc because of their established regulatory roles in the control of transcriptional programs that govern fatty acid degradation and synthesis, respectively. Moreover, we thought their distinct activation processes and sensitivity to various stimuli make them very... 

The utilization of acetyl-CoA by the tricarboxylate cycle is dependent upon the availability of an appropriate intramitochondrial concentration of oxaloacetate which is maintained by anaplerotic reactions (Section 12.6). The intracellular concentration of oxaloacetate therefore depends upon the levels of certain glycolytic intermediates. If carbohydrate metabolism is depressed and fatty acid degradation predominant such as during starvation, fasting or diabetes mellitus, acetyl-CoA cannot enter the tricarboxylate cycle and is utilized by a reaction sequence leading to ketone body formation. There are three so-called ketone bodies ... 

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