Purine deoxyribonucleotides formation

Purine Biosynthesis Is Regulated at Two Levels Pyrimidine Biosynthesis Is Regulated at the Level of Carbamoyl Aspartate Formation Deoxyribonucleotide Synthesis Is Regulated by Both Activators and Inhibitors... 

Inhibition of nudeobase synthesis (2). Tet-rahydrofolic acid (THF) is required for the synthesis of both purine bases and thymidine. Formation of THF from folic acid involves dihydrofolate reductase (p. 274). The folate analogues aminopterin and methotrexate (amethopterin) inhibit enzyme activity. Cellular stores of THF are depleted. The effect of these antimetabolites can be reversed by administration of folinic acid (5-formyl-THF, leucovorin, citrovorum factor). Hydroxyurea (hydroxycarbamide) inhibits ribonucleotide reductase that normally converts ribonucleotides into deoxyribonucleotides subsequently used as DNA building blocks. 

Cobalamin enzymes, which are present in most organisms, catalyze three types of reactions (1) intramolecular rearrangements (2) methylations, as in the synthesis of methionine (Section 24.2.7) and (3) reduction of ribonucleotides to deoxyribonucleotides (Section 25.3). In mammals, the conversion of 1-methylmalonyl CoA into succinyl CoA and the formation of methionine by methylation of homocysteine are the only reactions that are known to require coenzyme Bj2. The latter reaction is especially important because methionine is required for the generation of coenzymes that participate in the synthesis of purines and thymine, which are needed for nucleic acid synthesis. 

Many LactobaciUus species have an absolute growth requirement for a purine, a pyrimidine, and a single deoxyribonudeoside of any sort because the entire complement of cellular deoxyribonucleotides is derived from these materials, there is an evident requirement for the capability of transferring the deoxyribosyl function between bases in these cells. However, in lactobacilli deoxyribosyl transfer is not accomplished by the phosphorylase mechanisms outlined above in this connection it may be noted that lactobacilli are devoid of thymidine phosphorylase (4). A specific enzyme activity, deoxyribosyl transfer in these bacteria this is accomplished without the intermediate formation of deoxyribose 1-phosphate, is readily reversible, and takes place in the absence of inorganic phosphate ... 

For the former, the ribosomal pathway, the place to start, is with the genetic code and the carrier of the code, DNA. For the most general case, and as will be seen subsequently (Chapter 14), DNA is composed of four deoxyribonucleotides (i.e., monophosphate ester derivatives of deoxynucleosides) (Figure 12.11) held in chains (Figure 12.12) by the formation of phosphate diesters, linearly from one deoxyribose (5 ) to the next (3 ). The chains are paired, in the classical helical structure, by hydrogen bonding between the purine and pyrimidine bases (A-T and C-G) on opposite chains (Figure 12.12). ... 

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