Enzymes formaldehyde-activating

Biological systems overcome the inherent unreactive character of 02 by means of metalloproteins (enzymes) that activate dioxygen for selective reaction with organic substrates. For example, the cytochrome P-450 proteins (thiolated protoporphyrin IX catalytic centers) facihtate the epoxidation of alkenes, the demethylation of Al-methylamines (via formation of formaldehyde), the oxidative cleavage of a-diols to aldehydes and ketones, and the monooxygenation of aliphatic and aromatic hydrocarbons (RH) (equation 104). The methane monooxygenase proteins (MMO, dinuclear nonheme iron centers) catalyze similar oxygenation of saturated hydrocarbons (equation 105). ... 

Hagemeier, C.H., Griesinger, C., and Vorholt, J.A. (2002) A glutathione-dependent formaldehyde-activating enzyme (Gfa) from Paracoccus den-itrijicans detected and purified via two-dimensional proton exchange NMR spectroscopy. /. Biol. Chem., 277,... 

It is not known how N, N -methylenetetrahydro-folate is formed in tissues. In the laboratory, formylal-dehyde mixed with tetrahydrofolate results in spontaneous formation of the N, N -methylenetetrahy-drofolate. In tissues, a formaldehyde-activating enzyme probably catalyzes the condensing of formaldehyde with tetrahydrofolate. 

The authenticity of the enzymically formed active formaldehyde was established by its reactivity in serine biosynthesis and its oxidation to... 

A subclass of lyases, involved in amino acid metabolism, utilizes pyridoxal 5-phosphate (PLP, 3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinecarbaldehyde) as a cofactor for imine/ enamine-type activation. These enzymes are not only an alternative to standard fermentation technology, but also offer a potential entry to nonnatural amino acids. Serine hydroxymethyl-tansferase (SHMT EC 2.1.2.1.) combines glycine as the donor with (tetrahydrofolate activated) formaldehyde to L-serine in an economic yield40, but will also accept a range of other aldehydes to provide /i-hydroxy-a-amino acids with a high degree of both absolute and relative stereochemical control in favor of the L-erythro isomers41. 

Red blood cells also contain sufficient acid phenylphospha-tase for mild hemolysis to cause false elevations. Therefore, inhibitors such as ethanol, formaldehyde, copper sulfate> and 1-tartrate have been used to inhibit selectively the enzyme of one or more tissues and enhance the specificity of the test (101). Ethanol is unsuitable because it inhibits the enzyme from erythrocytes and prostate simultaneously, and because it yields serum activities which correlate poorly with prostatic disease. Formaldehyde inhibits the erythrocytic enzyme and has been said to yield clinically satisfactory results. The copoper resistant acid phosphatase of serum is elevated by metastatic carcinoma of the breast, as well as by other metastatic cancers, and is also elevated by a wide variety of non-cancerous diseases. 

The three different enzymes used in combination in this system were FateDH, FaldDH, andADH. FateDH catalyzes the initial reduction of C02 to formate, FaldDH the reduction of formate to formaldehyde, and ADH the reduction of formaldehyde to methanol. Interestingly, the enzymes when immobilized were more active than a combination of the free enzymes, which is claimed to be due to a reduction of spatial interference among the different enzymes. Moreover, due to the immobilization of enzymes within the microreactor, the intermediate species have significantly reduced distances to travel between active sites [21, 22]. 

The successful of recovery of RNase A functional activity by a heat-induced AR method suggested the possibility of recovering RNase A immunoreactivity as well. The immunoreactivity of native RNase A and RNase A that was incubated at a concentration of 4 mg/mL in 10% neutral buffered formalin for 1 day and then freed of formaldehyde by dialysis against PBS was compared using capture enzyme-linked immunosorbent assay (ELISA). Selected fractions that... 

Formaldehyde solutions prepared by dissolving and depolymerization of paraformaldehyde (a homopolymer of formaldehyde with empirical formula HO (CH20)nH, where n > 6) are free of admixtures of methanol and formic acid. Depolymerized paraformaldehyde is useful in enzyme histochemistry, when the preservation of the enzyme activity is of crucial importance, but it has no advantage over formalin solutions routinely used in pathology and in immunohistochemistry. 

Human colon microsomal cytochrome P450 enzymes can demethylate 1,2-dimethylhydrazine, yielding formaldehyde, and activities in the descending colon are always higher than in the ascending or transverse colon (Newaz et al., 1983). A-Demethylation was also detected in microsomes from a human colon tumour line, adenocarcinoma LS 174T cells. The activity was inducible by phenobarbital and/or hydrocortisone. 

TA medical therapy based on competition at the active site is used to treat patients who have ingested methanol, a solvent found in gas-line antifreeze. The liver enzyme alcohol dehydrogenase converts methanol to formaldehyde, which is damaging to many tissues. Blindness is a common result of methanol ingestion, because... 

After receiving his Ph.D., Dr. French spent two years, 1942 to 1944, as a post-doctorate fellow in the laboratories of Professors J. D. Edsall and E. J. Cohn at Harvard Medical School. During this period, French worked in the area of amino acids and proteins, and he became especially interested in relating the structure of amino acids and proteins to chemical reactivity. With Dr. Edsall, he published an excellent review on the reactions of formaldehyde with amino acids and proteins. In this stage of his career, his interest was aroused in proteins that possess enzymic activity. In later years, much of his research was devoted to enzymes and their mode of action, and to the molecular mechanisms and theoretical aspects of enzyme action. 

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