Glycine purine metabolism

Sterol biosynthesis Bile acid biosynthesis C2rSteroid hormone metabolism Androgen and estrogen metabolism Nucleotide Metabolism Purine metabolism Pyrimidine metabolism Nucleotide sugar metabolism Amino sugar metabolism Amino Acid Metabolism Glutamate metabolism Alanine and aspartate metabolism Glycine, serine, and threonine metabolism... 

Folic acid serves as a carrier of one-carbon groups in many metabolic reactions. It is required for the biosynthesis of compounds such as choline, serine, glycine, purines, and deoxythymidine monophosphate (dTMP). 

In 1969, Diamond, Friedland, Halberstam and Kaplan (1), in attempting to develop a model for the study of purine metabolism in vitro in an intact human cell system, chose to study leucocytes because of the ease with which they can be obtained and their relative resistance to non-physiological conditions (2). Glycine-... 

It has long been established that glycine incorporation into uric acid, in vivo, is enhanced in certain patients with primary or idiopathic gout (7,8). Since increased glycine incorporation into uric acid precursors can also be demonstrated in vitro in the leucocytes of patients with primary gout, a readily accessible model may be available for the study of purine metabolism in these patients, and other groups as well. 

Studies on purine metabolism For the measurement of the de novo purine synthesis 10 juCi glycine-Cl4 (U) were administered orally in the morning to the patients who were on a low purine diet Following glycine-Cl4 administration the urines were collected in 3 portions on the first day and in one portion on the remaining days 5 rol urine were applied to a Dowex cation-exchange column (Dowex 50 fX 4, 200 - 400 mesh ... 

The effect of a purine-free diet on purine metabolism was studied in mice to ascertain whether the de novo purine synthesis could be altered. It was found that neither were body adenine pools depleted after feeding the diet for 10 weeks, nor was the rate of purine synthesis de novo from glycine-2-C measurably increased in these mice (4 4)- This suggested that the de novo synthetic capacity was adequate to meet the requirements of the mouse without difficulty. ... 

A number of the features of the purine metabolism of these patients are shown in Table 1, In both patients hyperuricemia is moderately severe and each excretes between two and four times the normal quantity of uric acid per day in the urine while receiving a purine-free diet. In both patients the rate of purine synthesis de novo, measured by the incorporation of l C-glycine into urinary uric acid, is increased 3.0- to 4,0-fold beyond that seen in normal individuals. The urinary uric acid/creatinine ratios in these patients are, as expected, increased above normal. Both APRT and... 

Durre P, JR Andreesen (1983) Purine and glycine metabolism by purinolytic Clostridia. J Bacteriol 154 192-199. 

It plays a vital role in various intracellular reactions e.g. conversion of serine to glycine, synthesis of thymidylate, synthesis of purines, histidine metabolism etc. Due to folic acid deficiency these reactions are affected. 

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. 

The coenzyme form of folic acid is tetra hydro folic acid (Figure 6.9). Tetrahydro folic acid is associated with one carbon metabolism. The tetrahydro folic acid serves as a carrier of single carbon moieties such as formyl, methenyl, methylene, formyl or methyl group. (Figure 6.10). It is involved in the biosynthesis of purines, pyrimidines, serine, methionine and glycine. 

Inhibition of the Reductase affects folate metabolism leading to decreased glycine formation from serine and decreased purine synthesis which requires CH3-THF. To facilitate normal cells folinic acid (Leucovorin) is given along with methotrexate. This acid aids normal cells by its conversion to the coenzyme of Thymidyiate S)mthetase, thus bypassing the block. Since the thymidine nucleotide requirements of rapidly proliferating cells are much greater than for quiescent cells folinic acid cannot meet the demands of the cancer cells. 

These cocnxymes derived from folic acid participate in many imponant reactions, including conversion ofhomocys-Icine to methionine, synthesis of glycine from serine, purine synthesis (C-2 and C-8). and hi.stidine metabolism. 

Once inside the cell, folates participate in a number of interconnected metabolic pathways involving (1) thymidine and purine biosynthesis necessary for DNA synthesis, (2) methionine synthesis via homocysteine remethylation, (3) methylation reactions involving S-adenosylmethionine (AdoMet), (4) serine and glycine interconversion, and (5) metabolism of histidine and formate (see Figure 8). Via these pathways. 

In most studies no significant increase in serum uric acid values have been found (Al, T8, Wl), but in some an increase has been reported (B8, S24). The work of Eisen and Seegmiller (E3) is the only report concerned with the metabolic formation of uric acid using radioactive glycine. They did show an increase in the formation of uric acid in extensive psoriasis and a reduction to normal levels with treatment. In addition, the excretion of pseudouridine and uracil was increased in extensive psoriasis (E2) (Table 13). There was a direct correlation in the above studies between the serum uric acid level versus the extent of skin involvement, the excretion of pseudouridine versus the extent of skin involvement, and also the excretion of pseudouridine versus the uric acid excretion (E = 0.81). These findings imply increased nucleic acid synthesis and increased nucleic acid breakdown in the skin, access of the purine breakdown products to the blood stream and from there to the liver ( ) for transformation into uric acid and finally to the kidney for excretion. 

Glycine is also important in the synthesis of purines. In mammals, this is a qualitatively important process, but is not a major flux for either glycine or nitrogen. This is in contrast to observations in birds and reptiles, where purines are the end product of nitrogen metabolism. Glycine is also an important precursor of porphyrins, which can then proceed to form hemes... 

See also De Novo Biosynthesis of Purine Nucleotides, DHF, THF, 10-FormyItetrahydrofolate, Adenosylmethionine and Biological Methylation, Metabolism of Serine, Glycine, and Threonine, Dihydrofolate Reductase, FdUMP, Vitamin B12 Coenzymes... 

N-Methylation yields the monomethyl derivative sarcosine and also dimethylglycine, compounds that may function as osmoprotectants (Box 20-C). Many bacteria produce sarcosine oxidase, a fla-voprotein that oxidizes its substrate back to glycine and formaldehyde, which can react with tetrahydro-folate. The formation of porphobilinogen and the various pyrrole pigments derived from it and the synthesis of the purine ring (Chapter 25) represent two other major routes for glycine metabolism. 

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