THE UTILIZATION OF FATTY ACIDS

CONTENTS Acknowledgments, Margery G. Ord and Lloyd A. Stocken. Introduction. Biochemistry Before 1900. Early Metabolic Studies Energy Needs and the Composition of the Diet. Carbohydrate Utilization Glycolysis and Related Activities. Aspects of Carbohydrate Oxidation, Electron Transfer, and Oxidative Phosphorylation. Amino Acid Catabolism in Animals. The Utilization of Fatty Acids. The Impact of Isotopes 1925-1965. Biochemistry and the Cell. Concepts of protein Structure and Function. Chronological Summary of Main Events Up to ca. 1960. Principal Metabolic Pathways. Index. 

The Utilization of Fatty Acids as Fuel Requires Three Stages of Processing... 

Finally, there is also an anaerobic pathway for fatty acid degradation in E. coli that is shared by other gram-negative bacteria [19]. This system allows the utilization of fatty acids in the anaerobic intestinal environment. 

In the liver, mitochondrial fatty acid oxidation and TG-biosynthesis are the major competitors for the utilization of fatty acids as substrate. The regulatory interrelationship between P-oxidation and TG-biosynthesis has not yet been elucidated in detail by fibrates and n-3 fatty acids. Growing evidence indicates that availability of TG is a major driving force in the secretion of TG-lipoproteins by the liver. It is, therefore, conceivable that factors influencing TG-biosynthesis of fatty acid oxidation may ultimately influence plasma lipoprotein levels and metabolism. 

Prevention of fatty livers. Choline is a lipotropic agent lipotropic means having an affinity for fat. In this role, choline prevents the abnormal accumulation of fat in liver (fatty liver) by promoting its transport as lecithin or by increasing the utilization of fatty acids in the liver itself. Without choline, fatty deposits build up inside the liver, blocking its hundreds of functions and throwing the whole body into a state of ill health. 

Historically, many attempts have been made to systematize the arrangement of fatty acids in the glyceride molecule. The even (34), random (35), restricted random (36), and 1,3-random (37) hypotheses were developed to explain the methods nature utilized to arrange fatty acids in fats. Invariably, exceptions to these theories were encountered. Plants and animals were found to biosynthesize fats and oils very differently. This realization has led to closer examination of biosynthetic pathways, such as chain elongation and desaturation, in individual genera and species. 

Several additional points should be made. First, although oxygen esters usually have lower group-transfer potentials than thiol esters, the O—acyl bonds in acylcarnitines have high group-transfer potentials, and the transesterification reactions mediated by the acyl transferases have equilibrium constants close to 1. Second, note that eukaryotic cells maintain separate pools of CoA in the mitochondria and in the cytosol. The cytosolic pool is utilized principally in fatty acid biosynthesis (Chapter 25), and the mitochondrial pool is important in the oxidation of fatty acids and pyruvate, as well as some amino acids. 

The role of fatty acids as oxidizable fuels for brain metabolism is negligible, but ketone bodies, derived from fatty acid oxidation, can be utilized, particularly in the neonatal period. Diseases of carbohydrate and fatty acid metabolism may affect the brain directly or indirectly [1,10]. 

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. 

This sequence of reactions, namely oxidation of CH2-CH2 to CH=CH, then hydration to CH2-CHOH, followed by oxidation to CH2-CO, is a sequence we shall meet again in the -oxidation of fatty acids (see Section 15.4.1). The first oxidation utilizes FAD as coenzyme, the second NAD+. In both cases, participation of the oxidative phosphorylation system allows regeneration of the oxidized coenzyme and the subsequent generation of energy in the form of ATP. 

Another source of rubredoxins was found in an aerobic bacterium, Pseudomonas oleovorans, utilizing n-hexane as a carbon source (10). This particular rubredoxin differs from those commonly found in anaerobic bacteria in some of its properties it has a molecular weight of 19,000, and one iron form of the protein is readily converted to a two-iron form (11). The rubredoxin of P. oleovorans functions as a terminal electron transfer component in an enzyme system which participates in the ( -hydroxylation of fatty acids and hydrocarbons. The hydrocarbon-oxidizing... 

At the beginning of this century the production of plant lipases was performed by mechanical dismption of the seed of ricintrs after procedures of Nicloux and Hoyer. These lipases were utilized for the production of fatty acids from oils and fats. 

Whereas in acetonitrile the number of double bonds seems to be more important for solubility, in methanol the chain length seems more important. Utilization of the different properties of these two solvents offers some possibility for the separation of fatty acids whose differences in chain length and degree of unsaturation may make them difficult to separate with the use of either acetonitrile or methanol alone. 

The level of fatty acids in the bloodstream is one factor that dictates how much fatty acid is delivered to a tissue. Further controls are necessary in the cell to regulate the utilization... 

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