Lipids fatty acid oxidation

Green, D.E. Gibson, D.M. (1960). Fatty acid oxidation and synthesis. In Metabolic Pathways (Greenberg, D.M. Ed.) Vol. I, pp. 301-340. Academic Press, New York. Lipmann, F. (1948-1949). Biosynthetic Mechanisms. Harvey Lectures XLIV, 99-123. Vagelos, P.R. (1964). Lipid metabolism. Annu. Rev. Biochem. 33, 139-172. 

Fatty acid utilized by muscle may arise from storage triglycerides from either adipose tissue depot or from lipid stores within the muscle itself. Lipolysis of adipose triglyceride in response to hormonal stimulation liberates free fatty acids (see Section 9.6.2) which are transported through the bloodstream to the muscle bound to albumin. Because the enzymes of fatty acid oxidation are located within subcellular organelles (peroxisomes and mitochondria), there is also need for transport of the fatty acid within the muscle cell this is achieved by fatty acid binding proteins (FABPs). Finally, the fatty acid molecules must be translocated across the mitochondrial membranes into the matrix where their catabolism occurs. To achieve this transfer, the fatty acids must first be activated by formation of a coenzyme A derivative, fatty acyl CoA, in a reaction catalysed by acyl CoA synthetase. 

Fatty acids Despite the fact that fatty acids are lipid soluble, so that they will diffuse across membranes without a transporter, one is present in the plasma membrane to speed up entry into the cells, so that it is sufficient to meet the demand for fatty acid oxidation. Triacylglycerol transport into cells also depends on the fatty acid transporter. Since it is too large to be transported per se, it is hydrolysed within the lumen of the capillaries in these tissues and the resultant fatty acids are taken up by the local cells via the fatty acid transporter (Chapter 7). Hence the fatty acid transporter molecule is essential for the uptake of triacylglycerol. 

Schulz, H., Oxidation of fatty acids. In D. E. Vance, and J. E. Vance (eds.), Biochemistry of Lipids, Lipoproteins and Membranes. Amsterdam Elsevier Science Publishers, 1991. Provides an advanced and current summary of fatty acid oxidation in prokaryotes and eukaryotes. 

Biochemical stress can be minimized by using frequent feedings to minimize dependence on fatty acid oxidation, particularly for the liver. Meals should have a high-carbohydrate, low-fat content. Medium-chain triglycerides (synthetic or derived from coconut or palm kernel oils) can be used as these lipids can be oxidized independent of carnitine. These steps are particularly important when any external metabolic stress, such as a viral illness, is present. 

In addition, hepatic fatty acid oxidation is also required to sustain gluconeogenesis. These fatty acids may be obtained from exogenous feeding or metabolism of fatty acids released from endogenous lipid stores. (3-Oxidation of fatty acids provides the acetyl-CoA needed to activate mitochondrial pyruvate carboxylase and the NADH used as the substrate in the reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase in the direction of gluconeogenesis (see Fig. 10-1). 

Insulin is probably the most important inhibitor of lipolysis. In contrast to adults, in whom catecholamines represent the most important stimulators of lipolysis, thyrotropin (TSH) is the most important stimulator of lipolysis in the newborn. Plasma free fatty acid concentrations rise markedly in the first hours after birth in response to a marked increase in the TSH concentration and a fall in the insulin concentration. The fatty acids released from lipid stores are oxidized by some extrahepatic tissues (e.g., heart and skeletal muscle, kidney, intestine, and lung). Because the respiratory quotient (the ratio of carbon dioxide production to oxygen use) falls from a value of 1.0 (showing that carbohydrate oxidation is the primary source of energy) to a value of 0.8 to 0.9 (showing increasing oxidation of protein or fatty acids) at 2 to 12 hours of age, at a time when protein catabolism is usually insignificant, fatty acid oxidation must represent... 

The discovery of the statin mevalonic acid synthesis inhibitors focused new attention on control of blood lipid levels as a measure to stave off heart disease. A number of compounds have been found that treat elevated lipid levels by other diverse mechanisms. The phosphonic acid derivative ibrolipim (9) is believed to lower those levels by accelerating fatty acid oxidation. The phosphoms-containing starting material 7 can in principle be obtained by the Arbuzov reaction of a protected from of p-bromomethylbenzoic acid (6) with triethyl phosphate. Removal of the protecting group and conversion of the acid to an acyl chloride then affords 7. Condensation of this intermediate with substituted aniline 8 leads to the hypolipidemic agent (9). ... 

Fatty acid synthesis occurs in the cytoplasm, whereas fatty acid oxidation occurs in mitochondria. As mentioned previously, physicians are not so much interested in the intracellular localization of reactions as they are in the distribution of the reactions in the various organ systems. Lipids are such important components of cell membranes that the processes of lipid biosynthesis and degradation are near universal. Lipid" storage as triglycerides, however, is mainly a function of fat cells. 

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