Riboflavin synthesis

Pyrido[2,3-d]pyrimidine, 8-ribityl-as inhibitor of riboflavin synthesis, 3, 260 Pyrido[2,3-(i]pyrimidine, thioxo-reactions, 3, 211... 

This group includes the coenzyme forms of water-soluble vitamin B2 or riboflavin. Synthesis occurs by initial cyclohydrolase action on the guanine ring of GTP and subsequent steps lead to the synthesis of the isoalloxazine ring structure (see structures below). 

Both the fungus Eremothecium (Box 15-B) and mutants of Saccharomyces have been used to deduce the pathways of riboflavin synthesis outlined in Figure 25-20. The first reaction (step a) is identical to step a of Fig. 25-19 but is catalyzed by a different GTP cyclohydrolase.362 Instead of an Amadori rearrangement it catalyzes the hydrolytic deamination and dephosphorylation (step b) to give the flavin precursor... 

A number of fungi have a failure of the normal regulation of riboflavin synthesis and are overproducers of the vitamin. Mutants of Ashbya gossypii may accumulate up to 150 /xmol of riboflavin per gram of protein, compared with a normal content of 0.25 /xmol per gram of protein. They can produce and excrete so much that riboflavin crystallizes in the culture medium. Such fungi are used for the commercial production of riboflavin by fermentation, as an alternative to chemical synthesis. 

D. Revuelta G. Santos, etai., Riboflavin Synthesis in Yeast. W09411515, BASF AG, 1994. 

Barbituric acid had no effect on riboflavin synthesis when used as a rat dietary supplement. On the other hand, uric acid markedly decreased, whereas urea increased, riboflavin excretion [133]. 

The 5-amino derivative of cytosine is reported to inhibit riboflavin synthesis [399]. 4,5,6-Triaminopyrimidine inhibits both synthesis and growth by 60 per cent. 4,5,6-Triamino-2-hydroxypyrimidine inhibits synthesis, but not growth, of riboflavin [400]. 

Gelfand MS, Mironov AA, Jomantas J, Kozlov YI, Perumov DA A conserved RNA structure element involved in the regulation of bacterial riboflavin synthesis genes. Trends Genet 1999, 15(11) 439—442. 

It has been known for some time that addition of purines to incubation media stimulates riboflavin synthesis in certain microorganisms, and studies with labeled purines have shown that, as with folic acid, the C-8 of the purine ring is removed. Whether this takes place at the base, nucleoside, or nucleotide level is unclear. Guanine or xanthine is believed to be a proximal precursor in some cells, whereas hypoxanthine is believed to be involved in others. Figure 3-4 (see p. 50) shows one proposed scheme, although many details remain to be clarified. The biggest remaining question is the identity of the four-carbon unit which adds to the uracil derivative. 

Tracer studies and nutritional data on the stimulation of riboflavin synthesis (reviewed by Brown et al., 1958), show that rings B and C of riboflavin are derived from an intermediate related to the purines by a sequence summarized (XI) by Kuwadaef oZ. (1958), who isolated ribolumazine intermediates and aoetoin from Eremothedum ashbyii. 

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