Nonenzymatic Processes

Lenthionine (53) is one of flavoring substances in Lentinus edodes (Berk.) Sing (67CPB988). It was proposed that 53 is produced by polymerization of the parent dithiirane (54), which was formed from lentinic acid (55) by enzymatic and then nonenzymatic processes (76TL3129 77MI1). 

The few reports on bioremediation of colored effluents by yeasts usually mention nonenzymatic processes as the major mechanism for azo dye decolorization [5-10]. In a first approximation based on the cellular viability status, these processes can be divided into two different types bioaccumulation and biosorption. Bioaccumulation usually refers to an active uptake mechanism carried out by living microorganisms (actively growing yeasts). The possibility of further dye biotransformation by redox reactions may also occur due to the involvement of... 

Lactone ring opening can be both enzymatic and nonenzymatic, but it appears that the two mechanistic routes are seldom distinguished in metabolic studies [2], Thus, a number of the reports published on metabolism of lactones assume enzymatic hydration and do not examine what the relative contribution of nonenzymatic processes may be. Like for lactonization reactions, only very few in vitro biochemical studies address the question of relative enzymatic contribution and mechanism. 

Such groups are relevant in our context since they occur in drugs, drug metabolites, prodrugs, and other xenobiotics. Their hydrolysis is essentially a nonenzymatic process, the rates depending not only on the biological context, but also on the structure and properties of the compounds. 

The bioavailability of azathioprine (80%) is superior to 6-MP (50%). After absorption azathioprine is rapidly converted by a nonenzymatic process to 6-MP. 6-Mercaptopurine subsequently undergoes a complex biotransformation via competing catabolic enzymes (xanthine oxidase and thiopurine methyltransferase) that produce inactive metabolites and anabolic pathways that produce active thioguanine nucleotides. Azathioprine and 6-MP have a serum half-life of less than 2 hours however, the... 

It may be concluded that both metal activation and metal inhibition follow the order of complex stability in enzymatic as well as nonenzymatic processes, and that this order cannot be observed at any one metal concentration when activation and inhibition occur simultaneously. However, the order is approximated by the sequence of peaks in a plot of activity vs. metal ion concentration. 

Recently, Senoh, Tokuyama, and Witkop (37) have studied a metal-activated enzymatic reaction in the presence and the absence of enzyme, and have discovered that the order of effectiveness of the metals is exactly the reverse in the enzymatic and nonenzymatic processes. The reaction was O-methylation of 3,4-dihydroxybenzaldehyde. In the absence of divalent metal ions, the nonenzymatic reaction yields very predominantly the paramethylated product in neutral solution, since the p-hydroxyl group is the more electronegative. Metal complex formation... 

Methyl iodide incubated with human erythrocytes conjugates nonenzymatically with glutathione. In addition, an enzymatic conjugation was apparent with erythrocytes from 10/17 donors, but even among these people, the nonenzymatic process was dominant (Hallier et al., 1990). 

In addition to deliberate enzyme-catalyzed processes, there are nonenzymatic processes that alter proteins. These include the degradative reactions described in Section 5 and also reversible reactions that may be physiologically important. For example, the N-terminal amino groups of peptides, and other amino groups of low p Ka can form carbamates with bicarbonate (Eq. 2-21 ).301-303 This provides an important mechanism of carbon dioxide transport in red blood cells (Chapter 7) and a way by which C02 pressure can control some metabolic processes. 

A clue comes from the fact that chemiluminescence is very common when 02 is used as an oxidant in nonenzymatic processes. The slow oxidation of alcohols, aldehydes, and many nitrogen compounds (Eqs. 23-43,23-44) is accompanied by emission of light... 

As before, the enzymatic reduction is the method of choice for the enantioselective reduction of purely aliphatic ketones and only in the case of fert-butyl methyl ketone could the bench mark of 90 % ee be crossed by the transfer hydrogenation and both other catalytic hydrogenation methods. However, substantial success in the hydrogenation of aromatic ketones by transition metal complexes with respect to the enantioselectivity and the activity (TON) strengthens the confidence that further progress is possible, enabling us to use some advantages of these nonenzymatic processes for extended application in the near future, for example in the facilitation of product isolation. 

Glutamic y-semialdehyde cyclizes with a loss of H2O in a nonenzymatic process to give A i-pyrroline-5-carboxylate, which is reduced by NADPH to proline. Alternatively, the semialdehyde can be transaminated to ornithine, which is converted in several steps into arginine (Section 23.4.1). 

Malic acid (hydroxybutanedioic acid) is a chemical intermediate and is also used as a food flavor enhancer. It can be made by several routes. U.S. 5,210,295 (to Monsanto) describes a nonenzymatic process. U.S. 4,772,749 (to Degussa) describes recovery of malic acid from the product of enzymatic conversion of fumaric acid. U.S. 4,912,042 (to Eastman Kodak) describes an enzymatic separation process for separating the L- and D-isomers. U.S. 5,824,449 (to Ajinomoto Co.) describes a selective fermentation from maleic acid. Estimate the cost of production of D-malic acid by each process and determine which is cheapest. 

Several other studies dedicated to the comparison of biocatalytic and nonenzymatic transformations have been published [56-58]. The major aspect can be summarized as follows if high substrate and product concentration can be reached using low-priced substrates, this will result in an advantage for biocatalytic methods relative to nonenzymatic processes, at least if highly enantioenriched products are needed. 

In a somewhat different interpretation of available data, Baynes and Thorpe (1999) have stressed the importance of the formation in diabetic tissues of reactive carbonyl compounds, produced by either metabolic or nonenzymatic processes that may or may not require oxygen. The excess of reactive carbonyls is proposed to then promote glycoxidation and lipoxidation so as to cause chemical modification of proteins. These... 

Under normal circumstances, cellular antioxidant defense mechanisms minimize any damage. ROS are also formed during nonenzymatic processes. For example, exposure to UV light and ionizing radiation cause ROS formation. 

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