Glycine formation

The pathways for thiamine biosynthesis have been elucidated only partiy. Thiamine pyrophosphate is made universally from the precursors 4-amino-5-hydroxymethyl-2-methylpytimidinepyrophosphate [841-01-0] (47) and 4-methyl-5-(2-hydroxyethyl)thiazolephosphate [3269-79-2] (48), but there appear to be different pathways ia the eadier steps. In bacteria, the early steps of the pyrimidine biosynthesis are same as those of purine nucleotide biosynthesis, 5-Aminoimidazole ribotide [41535-66-4] (AIR) (49) appears to be the sole and last common iatermediate ultimately the elements are suppHed by glycine, formate, and ribose. AIR is rearranged in a complex manner to the pyrimidine by an as-yet undetermined mechanism. In yeasts, the pathway to the pyrimidine is less well understood and maybe different (74—83) (Fig. 9). 

Connections One-carbon fragments in from serine, glycine, formate, and histidine... 

The perhydroxy radical formed on the y-carbon atom (Reactions 30 and 31) is a likely precursor of aspartic acid, which we have found in yields of G = 1.1 when PGA was irradiated in 0.1% solution in 02. Further oxidation and a decarboxylation step would be required to give aspartic acid. However, it is not yet known whether the aspartic acid is formed solely as a result of irradiation it may be formed from a labile precursor during acid hydrolysis of the polymer. Our results differ from those reported by Friedberg and Hayden, who found high yields of aspartic acid in PGA irradiated in the absence of 02 we found only traces of aspartic acid from solutions of PGA irradiated under N2 (Figure 3). Glycine formation was not affected by the presence of 02. 

Purine nucleotides can be synthesized in the organism from relatively simple building blocks ribose, phosphate, glycine, formate, aspartate, glutamine, and C02. The origin of each purine base component is summarized in Figure 10.5,... 

The imidazole carboxylate group is phosphoiylated again and the phosphate group is displaced by the amino group of aspartate. Thus, a six-step process links glycine, formate, ammonia, hicarhonate, and aspartate to form an intermediate that contains all but two of the atoms necessary for the formation of the purine ring. 

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. 

Boldyreva, E.V., Ivashevskaya, S.N., Sowa, H., Ahsbahs, H., Weber, H.-P. Effect of high pressure on the crystalline glycine formation of a new polymorph, Dokl. Akad. Nauk. 396 (2004) 358-361. 

Chang, C., Huang, A. H. C. Metabolism of glyoxalate in isolated spinach leaf peroxysomes. Kinetics of glyoxalate, oxalate, carbon dioxide, and glycine formation. Plant Physiol. 67, 1003-1006 (1981)... 

The rapid progress of the past few years on the biosynthesis of the purine ribonucleoside analogs has helped estabhsh several pathways by which these fungal products are formed. Although adenosine, adenine, glycine, formate and ribose or phosphorylated derivatives of adenosine play an important role in the biosynthesis of these compounds, we are only beginning to understand how some of these unique nucleosides are formed. In those examples cited where the precursor for the biosynthesis of antibiotics is known, we still know very little about the intermediates and the enzymatic steps involved. Future research now demands a more detailed exploration of the biosynthetic processes by cell-free enzymatic extracts and purified enzymes in order to elucidate a sequence of the various reactions that are involved in the formation of the ultimate product. 

High doses of threonine in adults have been used as tentative therapy for spastic syndromes, a therapy that probably acts through increased glycine formation. A negative effect of excessive threonine, which is abvmdant in bovine infant formula nutrition, has been considered in experimental studies on brain development, and it has been su ested that this happens through its conversion to glycine and serine, or through competition of amino acid transport across the blood-brain barrier. 

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