Tissues fatty acid utilisation

Figure 7.6 Release of fatty acids from the triacylglycerol in adipose tissue and their utilisation by other tissues. Fatty acids are long-chain fatty acids, abbreviated to FFA (see below). Hydrolysis (lipolysis) of triacylglycerol in adipose tissue produces the long-chain fatty acids that are released from the adipocytes into the blood for oxidation by various tissues by P-oxidation (see below).

There are two tissues that cannot use long-chain fatty acids, the small intestine and the brain. Both can, however, oxidise ketone bodies and therefore can restrict glucose utilisation. It is not known why these tissues do not oxidise fatty acids possibly the activity of the enzymes in oxidation is very low. 

The properties are as follows, (i) The activity of the protein (i.e. the inward transport of protons) is inhibited by ATP. (ii) The activity of the protein is increased by the presence of long-chain fatty acids, since they relieve the ATP inhibition, (iii) When mitochondria, isolated from brown adipose tissue, are incubated in the presence of fatty acids, there is a sharp increase in the rates of electron transfer, substrate utilisation and oxygen consumption, whereas the rate of ATP generation remains low. These studies indicate that the rate of proton transport, by the uncoupling protein, depends on the balance between the concentrations of ATP and fatty acids, (iv) In adipocytes isolated from brown adipose tissue, the rate of oxygen consumption (i.e. electron transfer) is increased in the presence of catecholamines. 

Changes in the blood levels of these hormones all contribute to regulation of blood glncose level in several conditions. After a meal glucose utilisation is increased, since insulin stimulates glucose uptake by muscle and inhibits release of fatty acids from adipose tissue. Physical activity... 

Blood-bome fuels are glucose, which is derived from liver glycogen, and fatty acids derived from adipose tissue. Uptake depends on the flow of blood through the muscle, the concentration of the fuel in the blood and the demand for ATP within the muscle. During sustained exercise the flow of blood to the muscle can increase up to 50-fold and the rate of utilisation of the fuel can increase to a similar extent, yet the concentration of the fuels in blood remains remarkably constant (Table 13.5). 

Figure 16.2 Redprocal relationship between the changes in the concentrations of glucose and fatty adds in blood during starvation in adult humans. As the glucose concentration decreases, fatty acids are released from adipose tissue (for mechanisms see Figure 16.4). The dotted line is an estimate of what would occur if fatty acid oxidation did not inhibit glucose utilisation. Such a decrease occurs if fatty acid oxidation in muscle is decreased by specific inhibitors.

This figure shows the way in which glucose or fatty acids (in the form of fatty acyl coenzyme A, acyl CoA) are utilised as a source of energy by tissue. It shows the incorporation of acetyl CoA into the citric acid cycle, and also the points at which connections are made with other areas of metabolism. Amino... 

An alternate route utilises malate nicotinamide adenine dinucleotide phosphate (NADP) dehydrogenase (decarboxylating) to form malate, and then conversion to oxalacetate within the citric acid cycle to citrate. The relative importance of these two routes probably depends upon the subcellular distribution of the relevant enzymes in the tissue or subcellular organelle under study. This is referred to in detail in a later section. It should also be noted that pyruvate can be incorporated into the citric acid cycle either as oxalacetate or via acetyl CoA into citrate. This alternative applies only to the glycolytic pathway fatty acid oxidation, which is an alternate pathway of energy production, terminates with acetyl CoA which can only enter the citric acid cycle as citrate. 

Many of these deficiency conditions in animals can be explained in terms of the role of TPP in the oxidative decarboxylation of pyruvic acid. On a thiamin-deficient diet animals accumulate pyruvic acid and its reduction product lactic acid in their tissues, which leads to muscular weakness. Nerve cells are particularly dependent on the utilisation of carbohydrate and for this reason a deficiency of the vitamin has a particularly serious effect on nervous tissue. Since acetyl coenzyme A is an important metabolite in the synthesis of fatty acids (see p. 220), lipogenesis is reduced. The pentose phosphate pathway is also impaired by a deficiency of thiamin but there is little effect on the activity of the citric acid cycle. 

Unlike the other B vitamins, choline is not a metabolic catalyst but forms an essential structural component of body tissues. It is a component of lecithins, which play a vital role in cellular structure and activity. It also plays an important part in hpid metabolism in the liver, where it converts excess fat into lecithin or increases the utilisation of fatty acids, thereby preventing the accumulation of fat in the hver. Choline is a component of acetylcholine, which is responsible for the transmission of nerve impulses. Finally, choline serves as a donor of methyl groups in transmethylation reactions that involve folic acid or vitamin B12- Although other compounds, such as methionine and betaine, can also act as methyl donors, they cannot replace choline in its other functions. 

Griffiths, G., Stymne, S. and Stobart, A.K. (1988b) The utilisation of fatty acid substrates in triacylglycerol biosynthesis by tissue-slices of developing safflower (Carthamus tinctorius L.) and sunflower (Helianthus annuus L.) cotyledons. Planta 173, 309-319. 

Scaife, J.R., Wahle, K.W.J. and Garton, G.A. (1978), Utilisation of methylmalonate for the synthesis of branched-chain fatty acids by preparations of chicken liver and sheep adipose tissue. Biochem. 176,799. 

Alcohols may be released from the esterified form by any of the hydrolytic or transesterification procedures described in Chapter 4. If a pure wax ester fraction is hydrolysed, the alcohols are obtained simply by solvent extraction of the alkaline solution. On the other hand, when other lipids are present, it is advisable to isolate them as a class by adsorption chromatography. TLC on layers of silica gel G with the elution system described for simple lipid separations in Chapter 2, i.e. with hexane-diethyl ether-formic acid (80 20 2 by volume) as the mobile phase, is usually used. With such a system, any secondary alcohols migrate ahead of primary alcohols, which in turn are slightly less polar than cholesterol diols migrate just in front of monoacylglycerols. If cholesterol is present in an extract, it may be necessary to re-run the plate in the same direction to obtain additional resolution and ensure that primary alcohols and cholesterol are fully separated. Procedures of this kind were utilised to isolate trace levels of fatty alcohols from animal tissues, for example [108,662,904]. When wax esters are transesterified, the methyl esters and free alcohols can be separated on a mini-column of... 

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