Mechanism lipase, molecular

T. Shibatani, K. Omori, H. Akatsuka, E. Kawai, H. Matsumae, Enzymatic resolution of diltiazem intermediate by Serratia marcescens lipase molecular mechanism of lipase secretion and its industrial application J. Mol. Cat. B. Enz. 2000, 10,141-149. 

Holm C et al Molecular mechanisms regulating hormone sensitive lipase and lipolysis. Annu Rev Nutr 2000 20 365. 

C. Holm, T. Osterlund, H. Laurell, and J.A. Contreras, Molecular mechanisms regulating hormone-sensitive lipase and lipolysis, Annu. Rev. Nutr.,... 

Under the influence of ACTH, free fatty acids and glycerol concentrations increase in adipose tissue. ACTH stimulates lipolysis in adipose tissue by activating a hormone-sensitive lipase. However, ACTH does not act directly on the lipase. There are at least two other intermediate messengers adenylate cyclase and cyclic adenylate. The molecular mechanism of action of ACTH on lipolysis will be discussed in more detail in the section devoted to adipose tissue metabolism. 

Figure 5 (pg. 694) shows how the chiral solvent molecules play an important role in the stereoselectivity of the enzyme. Thus, S-(+)-carvone maintains the S enantiopref-erence observed for achiral solvents and lipase B of C. antarctica [97], whereas R- —)-carvone changes the enantioselectivity over long reaction times. A molecular mechanics study of the stability of the diastereomeric complexes formed by both carvones and both enantiomers of the substrate was carried out. The results are shown in Fig. 6 (pg. 694). 

The catalytic alcohol racemization with diruthenium catalyst 1 is based on the reversible transfer hydrogenation mechanism. Meanwhile, the problem of ketone formation in the DKR of secondary alcohols with 1 was identified due to the liberation of molecular hydrogen. Then, we envisioned a novel asymmetric reductive acetylation of ketones to circumvent the problem of ketone formation (Scheme 6). A key factor of this process was the selection of hydrogen donors compatible with the DKR conditions. 2,6-Dimethyl-4-heptanol, which cannot be acylated by lipases, was chosen as a proper hydrogen donor. Asymmetric reductive acetylation of ketones was also possible under 1 atm hydrogen in ethyl acetate, which acted as acyl donor and solvent. Ethanol formation from ethyl acetate did not cause critical problem, and various ketones were successfully transformed into the corresponding chiral acetates (Table 17). However, reaction time (96 h) was unsatisfactory. 

Use of Pseudomonas cepacia lipase (lipase PS) or Porcine pancreatic lipase does allow for the enzymatic ROP of lactide. Matsumura and coworkers reported polymers with extraordinarily high molecular weights (Mw up to 270 kDa) and very narrow PDI (<1.3) [135-137]. However, high temperatures (130°C) were needed to achieve good conversions, and polymerizations proceeded only when conducted in bulk. It is conceivable that another non-enzymatic mechanism contributed in these polymerizations. In fact, Koning and coworkers synthesized copolymers... 

Studies of the ability of the lipase B from Candida antarctica (CAL-B) to catalyse the enantioselective aminolysis of esters by cis- and firms-2-phenylcycloalkanamines (54 n = 1, 3, 4) have been followed up by molecular modelling approaches in order to probe the lipase-catalysed aminolysis mechanism. CAL-B possesses a typical serine-dependent triad, so it was possible, with access to an X-ray crystal structure of CAL-B, to model a series of phosphonamidates (55 n = 1, 3, 4) as analogues of the tetrahedral intermediate (TI) resulting from attack of the amine on the carbonyl of the acyl-enzyme. The results suggested as the most plausible intermediate for the CAL-B-catalysed aminolysis a zwitterionic TI resulting from the direct His-assisted attack of the amine on to a C=0 group of the acyl-enzyme.80... 

Enzymatic polymerization of lactones is a promising approach and has been investigated by several workers [45,46,71-78]. Poly(e-CL) with Mn=14,500 and a molecular weight distribution of 1.23 has recently been reported using Pseudomonas sp. lipase as the catalyst [71]. A complex mechanism involving both ring-opening and linear condensation polymerizations has been proposed for the enzymatic polymerization of lactones. 

Enzymatic cleaners contain enzymes derived from animals, plants, or microorganisms. Plant and microorganism-derived enzymes may cause sensitization in many lens wearers (391). A list of commonly used enzymes is provided in Table 10. AU these enzymes are effective in removing deposits from the contact lens surface (392). They are biochemical catalysts that are specific for catalyzing certain chemical reactions. Those that aid in removing debris from contact lenses are protease (protein-specific enzyme), lipase (lipid-specific enzyme), and amylase (polysaccharide-specific enzyme). Such enzymes catalyze breakdown of substrate molecules— protein, lipid, and mudn— into smaller molecular units. This process yields fragments that are readily removed by mechanical force and rinsing. 

In an elegant recent work, Loos et al. [51, 52] reported the synthesis of polydialanine) via lipase-catalyzed ring-opening of 2-azetidinone (Scheme 5.4) (see Chapter 14 for details on the polymerization mechanism). After removal of cyclic side products and low-molecular-weight species, pure linear poly(P-alanine) was obtained. The average DP of the polymer obtained was limited to 8 because of the solubility of the polymer in the reaction medium. Control experiments with P-alanine as substrate confirmed that the ring structure of the 2-azetidinone was necessary to obtain the polymer. 

Lipases are usually active in aqueous systems as well as in organic solvents which makes them applicable not only for hydrolytic reactions but also for esterifications and transesterifications or for the formation of amides. These enzymes are known to accept a wide variety of substrates quite often with high enantioselectivity which makes them useful for chiral organic substrates. Numerous molecular modeling studies during the last decade describe these phenomena and provide us today with a clear picture of the mechanisms behind the enzymatic reaction particularly of CALB. Vicente Gotor, Karl Hult, and Romas J. Kazlauskas are three of the most cited names in this regard who have contributed fantastic work in this field. 

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