Triacylglycerols metabolism, control

Fig. 7. Neurohumoral control of the metabolic changes during the acute phase of septic shock. AVP, vasopressin SNS, sympathetic nervous system TAG, triacylglycerol FFA, free faty acid. (Reproduced with permission from Clin. Endocrinol. K. N. Frayn, 24,577-599, 1986, by copyright permission of Blackwell Science Ltd., Oxford, UK.)...

The major role of skeletal muscle is movement, which is described and discussed in Chapter 13). Nevertheless, since muscle comprises 40% of the body it is large enough to play a part in control of the blood concentrations of the major fuels glucose, fatty acids, triacylglycerol and some amino acids. Skeletal muscle contains the largest quantity of protein in the body, which is used as a source of amino acids under various conditions (e.g. starvation, trauma, cancer see above). It plays an important part in the metabolism, in particular, of branched-chain amino acids, glutamine and alanine, which are important in the overall metabolism of amino acids in the body (discussed below). 

The flow of intermediates through metabolic pathways is controlled by 1bir mechanisms 1) the availability of substrates 2) allosteric activation and inhibition of enzymes 3) covalent modification of enzymes and 4) induction-repression of enzyme synthesis. This scheme may at first seem unnecessarily redundant however, each mechanism operates on a different timescale (Figure 24.1), and allows the body to adapt to a wde variety of physiologic situations. In the fed state, these regulatory mechanisms ensure that available nutrients are captured as glycogen, triacylglycerol, and protein. 

Adipokinetic hormones control metabolism of insects during long-distance flight.359 363 In the migratory locust these hormones consist of a pair of related octapeptides and a decapeptide (Table 30-5). The hormones stimulate triacylglycerol lipase in the insects fat bodies, induce release of carbohydrates from body stores, and affect many other aspects of metabolism.363 Insects also have hormones of the insulin family, proteins consisting of disulfide-linked A and B chains as in insulin. The silkworm Bombyx mori has 38 genes for the insulinlike bombyxins, which are synthesized in the brain.364... 

In addition to the provision of fatty acids for triacylglycerol synthesis, the low but regulated rates of lipogenesis may be critical for overall control of fatty acid metabolism in humans. As discussed above, malonyl-CoA, which is the product of the ACC reaction and the only free intermediate of fatty acid synthesis, inhibits CPT-1 activity, and thereby prevents transport of fatty acids into mitochondria. Thus, the dual role of malonyl-CoA as an intermediate of fatty acid synthesis and as a regulator of fatty acid oxidation, prevents the operation of the futile cycle, in tissues where both fatty acid synthesis and oxidation can be active. 

The release of fatty acids from triacylglycerols in adipocytes is controlled by hormones. In a scheme that will look famihar from our discussions of carbohydrate metabolism, a hormone binds to a receptor on the plasma membrane of the adipocyte (Figure 21.3). This hormone binding activates adenylate cyclase. 

Metabolism of triacylglycerols in animals requires the interaction of lipoprotein lipase (involved in uptake of acyl chains from plasma) and hormone-sensitive lipase (involved in release of fatty acids from lipid stores). Some aspects of lipoprotein lipase action are discussed in Section 12.3 and the reader is also referred to Brockerhoff and Jensen (1974) and Jensen (1971). The enzyme is also known as clearing factor lipase, requires apo-Cn for activity and may be bound via heparan sulphate proteoglycan at the endothelial surface in vivo (Williams et aly 1983). Considerable work has been carried out on intracellular processing of the enzyme in active tissues (Cryer, 1981) and on the action of hormones in controlling the adipose and heart tissue enzymes (Ashby and Robinson, 1980 de Gasquet etaL, 1975). 

Thyroid hormones stimulate the rate of triacylglycerol biosynthesis in liver but have the opposite effect in adipose tissue. This may be due to an increased rate of general metabolic turnover rather than a specific effect on PAP. Recent research indicates that the hormones most immediately implicated in the control of PAP activity are the glucocorticoids. High serum cortisol concentrations are associated with most of the conditions described above that lead to an increased activity of PAP and an elevated rate of... 

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