Nucleotides sources/supply

Synthesis is regulated at several other places as well. After IMP is made the pathway splits to build either AMP or GMP. Enzyme XII, which catalyzes the first step from IMP to AMP, is itself slowed down by excess amounts of AMP. Similarly, the catalysis of the first step from IMP to GMP is inhibited by excess GMP. (Unlike King Midas, the enzymes can tell when they have too much of a good thing.) Finally, Enzyme XII uses GTP as an energy pellet because, if a lot of GTP is around, more A nucleotides (AMR, ADP and ATP) are needed to keep the supply in balance. The final step in the synthesis of GMP uses ATP as an energy source for similar reasons. ... 

For a long time it has not been known whether the brain itself supplies pyrimidine precursors for the synthesis of RNA de novo or whether these precursors must be supplied preformed from extraneural sources. Evidence has been obtained [192] that neural tissue has little capacity for synthesizing pyrimidine nucleotides for its own metabolic needs de novo. The incorporation studies in rats suggest that the brain utilizes preformed pyrimidines to a much greater extent than it utilizes the de novo pathway. This underlines the importance of the liver and other peripheral organs in the maintenance of normal RNA metabolism of the brain [192], although the brain contains the enzymes of pyrimidine synthesis de novo [193,194]. 

The chart in Fig. 2 shows an alternate path for the formation of dUMP by direct deamination of dCMP. This may be how cytidine could be converted to thymidylate in the cases cited above [125,126]. However, this deaminase is not usually detected in E. coli but is induced by infection with T(even) phages [132,133]. It has also been purified from chick embryo and mammalian tissues, and its properties have been extensively analyzed [134-136]. It acts as a typical allosteric enzyme in both the phage-infected E. coli and animal systems. Homotropic substrate interaction is evident, and this is modified by dCTP as an activator, and by dTTP (sometimes dGMP) as an allosteric inhibitor. This type of control apparently functions to regulate the level of dTTP by feedback inhibition and by activation when the supply of dTTP is depleted. Cytidine deaminase (EC 3.5.4.5) isolated from sheep liver [137] appears to have the same allosteric properties, with the same positive and negative effectors, as those of dCMP deaminase. The latter enzyme is also induced by phage infection in B. subtiUs, and in contrast to the deaminase from all other sources it does not show allosteric inhibition or activation by any nucleotide [138]. 

This may be done in several ways. Quantitative studies of the rates at which the intermediates are oxidized and formed would aim at comparing the measured rates with the minimum postulated rates calculated from and over-all rate of respiration. If the rates are below the postulated values, it remains doubtful that the reaction under discussion is an intermediate step in the main respiratory mechanism. The most direct proof of the participation of a reaction in the energy supply is the demonstration that the supposed intermediate steps can be coupled with the synthesis of energy-rich phosphate bonds. Since the oxidation of reduced pyridine nucleotide by O2, through the intermediation of the cytochrome system, is the main immediate source of energy for the generation of p3rrophosphate... 

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