Calcium lipase activation

Several studies have been conducted on calcium-fat interactions in human infants (64-70). Low synthesis of bile salts and low pancreatic lipase activity may be responsible for poorer fat utilization in infants than in adults (63,71). Fat from infant formulas may be lower than that from human milk because of the lack of a bile-stimulated lipase in the former (72). In infants, fat absorption tends to decrease with increase in fatty acid length, with lower degree of saturation, and with increase of total fat (3). Triglyceride structure may also influence fat absorption in the infant and, thus, indirectly, might also affect calcium absorption in the infant. 

Increase of free cytosolic calcium is toxic for various reasons. Among them are the diminution of ATP levels (Tsuji et al. 1994), the protease and lipase activation, and the FR production that causes a peroxidation of lipids. The inflow of calcium in the terminals could also increase the release of endogenous excitatory amino acids and propagate neuronal damage through positive feedback (Choi and Hartley 1993). Glutamic neurotoxicity mediated by calcium follows three stages ... 

Laminaria is a kelp that finds its place in the brown algae family. It has been an area of study for past many years, and its wonderful biological properties have always attracted medical professionals and researchers to explore more and more from this wonder kelp. The constituents of Laminaria include iodine, potassium, magnesium, calcium and iron. Iodine compounds, TEA-hydroiodide in particular, are great lipolytic agents as they stimulate lipase activity. Laminarins on the other hand are used as a tumor angiogenic blocker. 

P3. Posner, I., and Morales, A., Mechanisms of enzyme and substrate activation by lipoprotein lipase cofactors. I. A specific requirement of physiological concentrations of calcium for enzyme activity. J. Biol. Chem. 247, 2255-2265 (1972). 

At the end of the previous chapter, we discussed the medium dependence of the lipase-catalyzed synthesis of nifedipines, dihydropyridines with an aromatic substituent in the 4-position and often asymmetric ester derivatives in the 3- and 5-positions, which are active as calcium antagonists in cardiovascular therapy. At the Amano Company in Nagoya, Japan, lipase-catalyzed hydrolyses of methylene-oxypropionyl or -pivaloyl diesters with Amano PS (Pseudomonas sp.) lipase were found to yield varying enantiomeric excesses depending on the solvent in cyclohexane the different esters yielded half-esters with 88.8-91.4% e.e. (R)-specificity for a triple mutant ( FVL ) of Amano PS lipase, whereas the same transformation with the same enzyme in diisopropyl ether (DIPE) yielded between 68.1 and > 99% e.e. of the (S)-product (Chapter 12, Figure 12.10) (Hirose, 1992,1995). 

Four major enzyme groups are secreted lipolytic, proteolytic, amylolytic, and nucleic acid splitting enzymes. These pancreatic enzymes, some of which are secreted in multipile forms, possess specificities complementary to die intestinal membrane-bound enzymes (Tabic 1). Fresh, uncontsnkinated pancreatic juice is without proteolytic activity because these enzymes am in the form of inactive zymogens. An important fraction of the calcium in pancreatic juice accompanies the enzymes, especially ct-amylase. Human pancreatic juice is moat dose to that of the pig, with high proportions of lipase and a-amylase in comparison with other mammals [1]. Therefore, pig pancreas extract, pancreatin, has up to now been die oreferred enzvme source for therapeutic tuncreas substitution. 

Figure 4 Effect of iimting concentration of bile salts Hi physiological proportions on die activity of pancxeaiu lipase (HP standard LS7). Reaction condition are neutralized oKve oil, 100 g/U hydroxypropyl methylcdlulose, II g/L calcium, 10 mM NaCI, 100 mM and a mixture of bile salts (29.8ft glycocholale, 24.5ft glycocheDOdesoxy-cbolsle, 11.9ft gly cod eoxydiolate, 12.6ft taimocholaite, tanrochcDodesaxycholate,...

It is dear that the interconnection between the activities of the different lipolytic enzymes, where the first enzyme modifies the physicochemical state of the lipid substrate in such a way that it becomes available to another enzyme, is not only of prime importance for lipid digestion, but also results in a broad synergism between gastric lipase, colipase, pancreatic lipase, phospholipase As. calcium, caiboxylester Lipase, bite salts, and substrate interraecK tes [55,62-64]. 

It is known that a vast variety of enzymes use metal ions in acid/base catalysts. In some cases the role of the metal is to activate water directly, e.g. Zn(OH)2 becomes Zn(OH ) in carbonic anhydrase, but in others it may be that the metal just forms a particularly constructive (useful) H-bond network, e.g. calcium in phospholipase A2 and in staph, nuclease. Substitution of one metal by other metals is now a critical test of the precision of the catalytic site and we know that nickel does not substitute for zinc in carbonic anhydrase, although it binds, and that Sr(II) has a different activity in lipases and nucleases from Ca(II). It is the water in the coordination sphere which is partly responsible for these changes. 

Lipase has a molecular weight of about 40,000 Da and an isoelectric point (pi) of 8.56 (32). It is activated by calcium and inhibited by heavy metals. The optimum pH is 7.5-8.0, and the optimum temperature is 37°C. It is inactivated by heating at 60°C for 15 minutes. Rice bran lipase preferentially hydrolyzes fatty acids from the... 

Muitfay M, Rao GH, Robinson P, and Reddy R. (1995). Influx of extracellular calcium and agonist-coupling appear essoitial for the activation of thromboxane AfdepeadeiA phos dK>lipase A human platelets. Prostaglandin Leuk. Essen. Fatty Acids. 53,31-39. 

The types of enzymes used by organic chemists vary widely and include such well-known biocataiysts as lipases, esterases, oxidoreductases, oxinitrilases, transferases and aldolases [4]. An example which illustrates the industrial application of a lipase concerns the kinetic resolution of a chiral epoxy ester used as the key intermediate in the synthesis of the calcium antagonist Diltiazem, a major therapeutic in the treatment of high blood pressure [6] (Fig. 1). In developing the industrial process for the production of this drug, many different lipases were screened, but only the bacterial lipase from Serratia marescens showed both a sufficiently high activity and enantioselectivity. The intermediate is produced industrially on a scale of 50 tons/year. 

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