Enzymes glycine reductase

Arkowitz RA, RH Abeles (1989) Identification of acetyl phosphate as the product of clostridial glycine reductase evidence for an acyl enzyme intermediate. Biochemistry 28 4639-4644. 

Hermann K, Andreesen JR. 1989. Reductive cleavage of sarcosine and betaine by Eubacterium acidaminophilum via enzyme systems different from glycine reductase. Arch Microbiol 153 50-9. 

GLYCINE REDUCTASE GLYCINE SYNTHASE Glycogen debranching enzyme, DEBRANCHING ENZYME Glycogenolysis tracer kinetics,... 

Excessive activity of the enzyme aldose reductase sometimes accompanies diabetes. The net result is often accumulation of reduced sugars such as galactose in the lens of the eye and ensuing cataract formation. A1 restatin (43), an aldose reductase inhibitor, is one of the first agents found that holds promise of preventing diabetes-induced cataracts. The compound, actually used as its sodium salt, is prepared in straightforward manner by imide formation between 1,8-naphthalic anhydride (41) and glycine. ... 

This enzyme also contains an N-terminal pyruvoyl residue as does one subunit of a selenium-containing glycine reductase which utilizes a dithiol to convert glycine into acetate with coupled formation of ATP ... 

The element Se—not really a metal—is known to play a key role in enzymes such as the well-known glutathione peroxidase, formate dehydrogenase, glycine reductase, and the previously mentioned hydrogenases (Chapter 9). The unusual amino acid selenocysteine has a unique codon on the DNA (TGA/UGA), but selenation of serine also appears to be possible [16]. A brief review on Selenium can be found in the literature [17],... 

Aminopterin and amethopterin are 4-amino analogues of folic acid (Fig. 11.5) and as such are potent inhibitors of the enzyme dihydrofolate reductase (EC 1.5.1.3) (Blakley, 1969). This enzyme catalyses the reduction of folic acid and dihydrofolic acid to tetrahy-drofolic acid which is the level of reduction of the active coenzyme involved in many different aspects of single carbon transfer. As is clear from Fig. 11.6, tetrahydrofolate is involved in the metabolism of (a) the amino acids glycine and methionine (b) the carbon atoms at positions 2 and 8 of the purine ring (c) the methyl group of thymidine and (d) indirectly in the synthesis of choline and histidine. 

Pyruvoyl cofactor is derived from the posttranslational modification of an internal amino acid residue, and it does not equilibrate with exogenous pyruvate. Enzymes that possess this cofactor play an important role in the metabolism of biologically important amines from bacterial and eukaryotic sources. These enzymes include aspartate decarboxylase, arginine decarboxylase," phosphatidylserine decarboxylase, . S-adenosylmethionine decarboxylase, histidine decarboxylase, glycine reductase, and proline reductase. ... 

Two enzymes that contain the pyruvoyl cofactor are not decarboxylases D-proline reductase and glycine reductase. These enzymes were originally reported to contain the pyruvate in an ester linkage, but later studies have demonstrated its presence at the N-terminus of one of the subunits linked by the peptide amide bond. In contrast to the pynivoyl-dependent decarboxylases, the site of internal cleavage and modification of these reductases is a cysteine rather than a serine. The mechanism of post-translational biosynthesis of the pyruvoyl cofactor in these enzymes could conceivably proceed through the same mechanism shown in Scheme 1 but with the cysteine sulfur performing the role of the serine oxygen. 

Clostridal glycine reductase is the bacterial enzyme which has been investigated most thoroughly . This enzyme catalyzes the reductive deamination of glycine to ammonia and acetate with the concomitant synthesis of ATP (Eq. 2). As has been... 

The ability of various diaminopyrimidines to distinguish between analogous forms of the enzyme dihydrofolate reductase is the basis of some of the best contemporary anti-malarial and anti-bacterial therapy (see Section 4.0, p. 123, Tables 4.1 and 4.2, and Section 9.3.3 and 9.6). Let us first look at the differences that exist between various vertebrate types of the enzyme, none of which is much inhibited by trimethoprim (4.P), and then proceed to invertebrate types, which are highly susceptible to this drug. The enzyme from chicken liver has only 75% identity of amino acid sequence with that from ox liver. Moreover, methylmercuric hydroxide activates the avian type twelvefold whereas it inactivates the bovine type. The avian type is much richer in basic amino acids and has an isoelectric point of 8.4 compared to 6.8 for the bovine type. This result is achieved in the avian type by the presence of lysine at positions 32,106, and 154, whereas the bovine type has glycine, threonine, and glutamic acid, respectively, in these positions (Kumars/a/., 1980). 

Cell A mutant K1 cell line of Chinese hamster ovary cells (CHO cells) which lacked the enzyme dihydrofolate reductase (DHFR) was used as a host cell (3). It could not grow without supplements, such as thymidine, glycine, and purine. The expression of DHFR was used as a selective maker of genetically modified cells. A culture medium was composed of a-Minimal Essential Medium (Sigma, St. Louis, MO) supplemented with 50 U/L Penicillin and 50U/L Streptomycin (Whittaker Bioproducts, Inc. Md.) and 5% dialyzed fetal bovine serum (Whittaker Bioproducts, Inc. Md.)... 

Folic acid (Fig. 6) is the precursor of a number of coenzymes vital for the synthesis of many important molecules. These derivatives of folic acid, referred to collectively as active formate and active formaldehyde , are responsible for the donation of one carbon fragments in the enzymatic synthesis of a number of essential molecules. In the formation of methionine from homocysteine, the folic acid coenzyme donates the S-methyl group, and in the conversion of glycine to serine it is necessary for the formation of the hydroxymethyl group. Folic add is converted into its active coenzyme forms by an initial two step reduction to tetra-hydrofolic add (Fig. 6) by means of two enzymes, folic reductase and dihydrofolic reductase. Conversion of tetrahydrofolic acid (THF) to an active coenzyme folinic acid subsequently occurs by ad tion of an Ns formyl group (Fig. 6). The formation of similar compounds such as an Nio formyl derivative, or the bridged Ns,Nio-methylenetetrahydrofolic acid, also leads to active coenzymes. 

FIGURE 40-3 Glycine cleavage system and some related reactions. Glycine and serine are readily interchangeable. Enzymes (1) Glycine cleavage system (2) and (4) Serine hydroxymethyltransferase (3) N5 10-methylenetetrahydrolate reductase. N5 I0-CH2-FH4, N5>10-methylenetetrahydrolate FH4, tetrahydrofolic acid. 

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