Fatty acids tissue utilization

Fatty acids are utilized as fuels by most tissues, although the brain, red and white blood cells, the retina, and adrenal medulla are important exceptions. Catabolism of fatty acids requires extramitochondrial activation, transport into mitochondria, and then oxidation via the /3-oxidative pathway. The initial step is catalyzed by fatty acyl-CoA synthetase (also called thiokinase and fatty acyl-CoA ligase), as shown in Equation (19.5). The product, fatty acyl-CoA, then exchanges the CoA for carnitine, as shown in Equation (19.6) ... 

The rate of mitochondrial oxidations and ATP synthesis is continually adjusted to the needs of the cell (see reviews by Brand and Murphy 1987 Brown, 1992). Physical activity and the nutritional and endocrine states determine which substrates are oxidized by skeletal muscle. Insulin increases the utilization of glucose by promoting its uptake by muscle and by decreasing the availability of free long-chain fatty acids, and of acetoacetate and 3-hydroxybutyrate formed by fatty acid oxidation in the liver, secondary to decreased lipolysis in adipose tissue. Product inhibition of pyruvate dehydrogenase by NADH and acetyl-CoA formed by fatty acid oxidation decreases glucose oxidation in muscle. 

The reason for the cholesterol-lowering effect of polyunsaturated fatty acids is still not fully understood. It is clear, however, that one of the mechanisms involved is the up-regulation of LDL receptors by poly-and monounsaturated as compared with saturated fatty acids, causing an increase in the catabolic rate of LDL, the main atherogenic lipoprotein. In addition, saturated fatty acids cause the formation of smaller VLDL particles that contain relatively more cholesterol, and they are utilized by extrahepatic tissues at a slower rate than are larger particles—tendencies that may be regarded as atherogenic. 

Besides water, the diet must provide metabolic fuels (mainly carbohydrates and lipids), protein (for growth and turnover of tissue proteins), fiber (for roughage), minerals (elements with specific metabolic functions), and vitamins and essential fatty acids (organic compounds needed in small amounts for essential metabolic and physiologic functions). The polysaccharides, tri-acylglycerols, and proteins that make up the bulk of the diet must be hydrolyzed to their constituent monosaccharides, fatty acids, and amino acids, respectively, before absorption and utilization. Minerals and vitamins must be released from the complex matrix of food before they can be absorbed and utifized. 

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. 

Long-chain fatty acyl-CoA synthetase [EC 6.2.1.3] catalyzes the reaction of ATP with a long-chain carboxylic acid and coenzyme A to produce an acyl-CoA, AMP, and pyrophosphate. While utilizing a wide range of long-chain saturated and unsaturated fatty acids as substrates, enzymes from different tissues vary in their specificity. 

Fatty acids are transported in the blood bound to albumin for uptake and utilization by other tissues. 

The 3-OH FAs have had great utility in the determination of LPS levels in indoor air. However, in tissues and body fluids it has been determined that 3-OH FAs are naturally present at low levels as products of mammalian metabolism (mitochondrial fatty acid p oxidation). Due to this background GC-MS/MS for 3-OH FAs is not recommended as a general marker to determine trace LPS levels in clinical samples [14]. However, in certain situations the assessment of 3-OH FAs has been successfully used, for example, in the diagnosis of chronic peridontitis [15]. There is great potential for the utility of 3-OH FAs as markers for LPS contamination in pharmaceutical products, where often the background matrix would be anticipated to be much less complex. 

Alpha oxidation and omega oxidation. Animal tissues degrade such straight-chain fatty acids as palmitic acid, stearic acid, and oleic acid almost entirely by (3 oxidation, but plant cells often oxidize fatty acids one carbon at a time. The initial attack may involve hydroxylation on the a-carbon atom (Eq. 17-3) to form either the d- or the L-2-hydroxy add.17 18-32 323 The L-hydroxy acids are oxidized rapidly, perhaps by dehydrogenation to the oxo acids (Eq. 17-3, step b) and oxidative decarboxylation, possibly utilizing H202 (see Eq. 15-36). The D-hydroxy acids tend to accumulate... 

Chromium also slimulales fatty acid and cholesterol synthesis from acetate in liver. Thai chromium is an essential cofaclor for the action of insulin on the rat lens was shown by Parkas in 1964. In the absence of the element, no significant insulin effect on glucose utilization of lens can be demonstrated. Chromium supplementation to the donor animals resulls in a significant response of lens tissue to the hormone. Numerous other findings indicate that chromium may play several vital roles in biological systems. 

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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