An enzyme of pyrimidine nucleotides biosynthesis …
A likely mechanism for the ribonucleotide reductase reaction is illustratedin Figure 16–7. The 3'-ribonucleotideradical formed in step 1 helps stabilize thecation formed at the 2' carbon after the loss of H2O(steps 2 and 3). Two one-electron transfers accompaniedby oxidation of the dithiol reduce the radicalcation (step 4). Step 5 is the reverse of step 1 , regeneratingthe active site radical (ultimately, the tyrosyl radical)and forming the deoxy product. The oxidized dithiolis reduced to complete the cycle (step 6). In E. coli,likely sources of the required reducing equivalents forthis reaction are thioredoxin and glutaredoxin, as notedabove.
Four classes of ribonucleotide reductase have been reported. Their mechanisms(where known) generally conform to the scheme in Figure 16–7, but they differ inthe identity of the group supplying the active-site radicaland in the cofactors used to generate it. The E. coli enzyme(class I) requires oxygen to regenerate the tyrosylradical if it is quenched, so this enzyme functions only inan aerobic environment. Class II enzymes, found in othermicroorganisms, have 5'-deoxyadenosylcobalamin rather than a binuclear iron center. Class IIIenzymes have evolved to function in an anaerobic environment.E. coli contains a separate class III ribonucleotidereductase when grown anaerobically; thisenzyme contains an iron-sulfur cluster (structurally distinctfrom the binuclear iron center of the class I enzyme)and requires NADPH and S-adenosylmethioninefor activity. It uses nucleoside triphosphates rather thannucleoside diphosphates as substrates. A class IV ribonucleotidereductase, containing a binuclear manganesecenter, has been reported in some microorganisms. Theevolution of different classes of ribonucleotide reductasefor production of DNA precursors in different environmentsreflects the importance of this reaction in nucleotidemetabolism.
it is a key enzyme in the interconversion of pyrimidine nucleotides.
The genetic component of cells (DNA, RNA polymers), but also important for cellular energy metabolism, signaling, and protein biosynthesis (RNA, single nucleotides).
Taken together, these results suggest that a better utilization of purine bases and nucleosides for nucleotide and nucleic acid synthesis, as well as a more rapid turnover of pyrimidine nucleotides, represent a physiological switch, which occurs during the initiation and continuation of the organogenic process in white spruce.">
Nucleotide Biosynthesis | Nucleotides | Biosynthesis
FIGURE 16–4 (a) De novo synthesis of pyrimidine nucleotides: biosynthesisof UTP and CTP via orotidylate. The pyrimidine is constructed from carbamoylphosphate and aspartate. The ribose 5-phosphate is then added to the completedpyrimidine ring by orotate phosphoribosyltransferase. The first step in thispathway (not shown here; is the synthesis of carbamoyl phosphate from CO2and NH4+, catalyzed in eukaryotes by carbamoyl phosphate synthetase II. (b)Channeling of intermediates in bacterial carbamoyl phosphate synthetase.(Derived from PDB ID 1M6V.) The large and small subunits are shown in gray andblue, respectively; the channel between active sites (almost 100 Å long) isshown as a yellow mesh. A glutamine molecule (green) binds to the small subunit,donating its amido nitrogen as NH4+ in a glutamine amidotransferase–typereaction. The NH4+ enters the channel, which takes it to a second active site,where it combines with bicarbonate in a reaction requiring ATP (bound ADP inblue). The carbamate then reenters the channel to reach the third active site,where it is phosphorylated to carbamoyl phosphate (bound ADP in red).
involved in pyrimidine biosynthesis
The structure of DNA is the double helix and in all organisms contains only two forms of base pair combinations - AT (TA) and GC (CG) - which determine and control the accurate copying of the nucleotide sequence during cell division or protein biosynthesis.
amounts of purine and pyrimidine nucleotides.
Ribose derivatives play a significant role in the body. Important ribose derivatives encompass those having phosphate groups attached at the 5 position, including mono-, di-, and triphosphate forms, and 3-5 cyclic monophosphates. Diphosphate dimers, known as coenzymes, form an essential class of compounds with ribose. When such purine and pyrimidine derivatives are coupled with ribose, they are known as nucleosides (bases attached to ribose). Phosphorylated nucleosides are known as nucleotides. When adenine (a purine derivative) is coupled to ribose it is known as adenosine. ATP is the 5’-triphosphate derivative of adenosine. (The adenine portion of ATP consists of ribose and adenine. The triphosphate portion of ATP consists of three phosphate molecules.)