Lipases triacylglycerol lipase

FIGURE 24.3 (a) A duct at the junction of the pancreas and duodenum secretes pancreatic juice into the duodenum, the first portion of the small intestine, (b) Hydrolysis of triacylglycerols by pancreatic and intestinal lipases. Pancreatic lipases cleave fatty acids at the C-1 and C-3 positions. Resulting monoacylglycerols with fatty acids at C-2 are hydrolyzed by intestinal lipases. Fatty acids and monoacylglycerols are absorbed through the intestinal wall and assembled into lipoprotein aggregates termed chylomicrons (discussed in Chapter 25). 

FIGURE 25.17 Hormonal signals regulate fatty acid synthesis, primarily through actions on acetyl-CoA carboxylase. Availability of fatty acids also depends upon hormonal activation of triacylglycerol lipase. 

Triacylglycerol lipase Lipase, triglyceride lipase Triglycerides... 

L. Brady, A. M. Brzozowski, Z. S. Derewenda, E. Dodson, G. Dodson, S. Tolley, J. P. Turkenburg, L. Christiansen, B. Huge-Jensen, L. Norskov, L. Thim, U. Menge, A Serine Protease Triad Forms the Catalytical Centre of a Triacylglycerol Lipase , Nature 1990, 343,161-110. 

The physiological pathway for oxidation of fatty acids in organs or tissues starts with the enzyme triacylglycerol lipase within adipose tissue, that is, the hormone-sensitive lipase. This enzyme, plus the other two lipases, results in complete hydrolysis of the triacylglycerol to fatty acids, which are transported to various tissues that take them up and oxidise them by P-oxidation to acetyl-CoA. This provides a further example of a metabolic pathway that spans more than one tissue (Figure 7.13) (Box 7.1). 

Figure 7.19 The physiological pathway for ketone body oxidation from triacylglycerol in adipose tissue to their oxidation in a variety of tissues/organs. The pathway spans three tissues/ organs. The flux-generating step is the triacylglycerol lipase and ends with CO2 in one or more of the tissues/organs.

The hypothesis that is formulated on the basis of these properties is as follows. The signal for increased thermogenesis, when the body temperature falls, is an increase in the level of catecholamines, probably the local concentration of noradrenaline, which will be increased via stimulation of sympathetic nervous system. The catecholamine increases the activity of triacylglycerol lipase within the brown adipose tissue, by a similar mechanism to that which occurs in white adipose tissue (Chapter 7), i.e. by an... 

Figure 9.29 Control of heat production in brown adipose tissue. Catecholamines increase cyclic AMP concentrab on which stimulates triacylglycerol lipase which increases the long-chain fatty acid level, which increases the fluxes through P-oxidation and the Krebs cycle, and the activity of the uncoupling protein. Uncoupling decreases the ATP concentration which further increases the activity of the uncoupling.

This enzyme [EC 3.1.1.34] (also called clearing factor lipase, diglyceride lipase, and diacylglycerol lipase) catalyzes the hydrolysis of a triacylglycerol to produce a diacylglycerol and a fatty acid anion. This enzyme hydrolyzes triacylglycerols in chylomicrons and in low-density lipoproteins and also acts on diacylglycerols. See also Lipases... 

Lipases are enzymes that catalyze the in vivo hydrolysis of lipids such as triacylglycerols. Lipases are not used in biological systems for ester synthesis, presumably because the large amounts of water present preclude ester formation due to the law of mass action which favors hydrolysis. A different pathway (using the coenzyme A thioester of a carboxylic acid and the enzyme synthase [Blei and Odian, 2000]) is present in biological systems for ester formation. However, lipases do catalyze the in vitro esterification reaction and have been used to synthesize polyesters. The reaction between alcohols and carboxylic acids occurs in organic solvents where the absence of water favors esterification. However, water is a by-product and must be removed efficiently to maximize conversions and molecular weights. 

Chylomicrons deliver tiiacylglycerols to tissues, where lipoprotein lipase releases free fatty acids for entry into cells. Triacylglycerols stored in adipose tissue are mobilized by a hormone-sensitive triacylglycerol lipase. The released fatty acids bind to serum albumin and are carried in the blood to the heart, skeletal muscle, and other tissues that use fatty acids for fuel. 

T Glycogen phosphorylase I Glycogen synthase I PFK-1 T FBPase-2 i Pyruvate kinase T PEP carboxykinase T Triacylglycerol lipase Perilipin phosphorylation T Acetyl-CoA carboxylase... 

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... 

Transesterification, fatty acid analysis of lipids, 437, 439 Triacetin, lipase assays, 378 Triacylglycerol acylhydrolase, 371, 375, 378. See also Lipases Triacylglycerols, 432 Tributyrin, lipase assays, 378 Trichloroacetic acid (TCA) solubility index for protein hydrolysis, 152 in TBARS determination, 548-550 Trienes, conjugated, determination of, 515-517, 523-524, 526, 528 Trifluoroacetic acid (TFA), for determination of neutral sugars, 721-722, 724-725, 729-730... 

Hydroxymethylglutaryl-CoA reductase Acetyl-CoA carboxylase Triacylglycerol lipase... 

When certain hormones (e.g., epinephrine) bind to their receptors in adipose tissue, adenylate cyclase is activated. The cAMP that is formed activates protein kinase A, which phosphorylates triacylglycerol lipase. The phosphorylated form of this enzyme is the active species, and triacylglycerols are degraded to fatty acids. 

Carboxylesterase Arylesterase Triacylglycerol lipase Phospholipase A2 Lysophospholipase Acetylesterase Acetylcholinesterase Cholinesterase... 

Lipases (triacylglycerol acyl hydrolases, EC 3.1.1.3), have been well established as a valuable catalyst in organic synthesis.12 They are usually distinguished from carboxyl esterases (EC 3.1.1.1) by their substrate spectra, i.e. esterases prefer water soluble substrates and lipases show significantly higher activity towards their natural substrates,... 

The major source of free fatty acids in the blood is from the breakdown of triacylglycerol stores in adipose tissue which is regulated by the action of hormone-sensitive triacylglycerol lipase (see Topic K4). Fatty acid breakdown and fatty acid synthesis are coordinately controlled so as to prevent a futile cycle (see Topic K3). 

Regulation The concentration of free fatty acids in the blood is controlled by the rate at which hormone-sensitive triacylglycerol lipase hydrolyzes the triacylglycerols stored in adipose tissue. Glucagon, epinephrine and norepinephrine cause an increase in the intracellular level of cAMP which allosterically activates cAMP-dependent protein kinase. The kinase in turn phosphorylates hormone-sensitive lipase, activating it, and leading to the release of fatty acids into the blood. Insulin has the opposite effect it decreases the level of cAMP which leads to the dephosphorylation and inactivation of hormone-sensitive lipase. 

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