The production of DNA nucleotides.

(i) DNA generation:

DNA nucleotides are generated by reducing the corresponding ICNs to replace hydroxyl on C2 in their UC Molecules with H, rather than synthesized from the DNA from the head. This reduction is performed at the level of nucleotides (NDP) for phosphate. (Here N stands for A, G, U, C, etc.).

< the enzyme > the catalytic DNA nucleotide is ribonudeotide reductase. Three different types of ICS reductase have been found, and the reaction process is more complex. The final step in the catalytic cycle reaction of the nucleotide reductase is the process of reducing the two sulfur bonds in the enzyme molecule to a -based enzyme regeneration process with reduced activity. Thioredoxin is a physiological reducing agent for this enzyme, consisting of 108amino acids with a molecular weight of about 12kD. Contains a pair of adjacent cysteine residues (Figure 8 11). The sulfur-containing sulfur base is oxidized to the sulfur bond under the action of the RNA reduction enzyme, which is then catalyzed in the thioredoxin reductase, which is restored from NADPH hydrogen supply to the prototype sulfur redox protein. Therefore, NADPH is the final reducing agent for NDP to dNDP. (Figure 8-12) .

ICT nucleotide reductase is a variant enzyme, including B1, B2 two sub-bases, only when B1 and B2 binding. is enzymatic. In cells with strong DNA synthesis and rapid division, the nucleotide reductase system is more active.

Figure 8-12 X-ray diffraction structure of E. coli sulfur redox protein

(ii) regulation of DNA synthesis

"tt1" four dNTP synthesis levels are fed back to adjust, while maintaining the appropriate proportion of dNTP is also necessary for the normal growth of cells. In fact, the absence of any kind of dNTP is fatal, and too much dNTP can also causemutation because too much dNTP can be mistakenly mixed into the DNA chain. The activity of the nucleotide reductase plays a decisive role in the level of DNA nucleotides. Various dNTPs regulate the production of different DNA nucleotides through a variant effect. Because when a particular NDP is produced by reductase, it needs to be promoted by a specific NTP and inhibited by other NTP (Table 8 2). The 4 dNTPs are adjusted to maintain an appropriate proportion.

table 8-2 ICSD reductase structure adjustment

< td align> "middle"

effects

main inhibitor< td align" >CDP< td align "middle" >ATPdATP, dGTP, dTTP. < td align> "middle" >UDP< "middle" >ATPdATP, dGTPADPdGTP< dATP, ATP GDP< td align"middle" >dTTPdATP

for example, When a mixed NDP substrate is present, THEP prompts CDP and UDP restore to generate doDDP and dCDP. After the dUDP is converted to dTTP (later), dTTP feedback inhibits CDP and UDP reduction, while promoting the generation of dGDP, dGDPphosphorylation generating dGTP inhibits the reduction of GDP, CDP and UDP, and promotes the reduction of ADP to generate dADP. When the datP elevation is combined with the active bits of the enzyme

Figure 8-13 DNA synthesis and regulation network

, the reduction reaction of all NDP is inhibited (Figure 8-13). The appropriate proportion of intracellular dCTP and dTTP is not regulated by UC nucleotide reductase, but is determined by deoxycytidine deaminase. This enzyme catalyzes the generation of dUMP, which is a prelude to dTTP. This enzyme is activated by dCTP and inhibited by dTTP.

dNTP is generated by dNDP phosphatization:

by diphosphate nucleotides(mucleoside diphosphafe kinase), catalytic and catalytic NDP phosphoric acid reaction.

(iii) deoxyrigen thyroid nucleotide generation

The significance of the reaction process of such "wave waste" energy in the body of the

is that cells must reduce the concentration of dUTP in cells to prevent deoxyriurealine from being incorporated into DNA, because the enzyme system of synthetic DNA does not effectively identify dutp and dTTP.

dUMP methylation generates dTMP catalytic by thymidylate synthase (thymidylate synthetase, TS), N5, N10-methylene FH4 provides methyl (Figure 8-14). N5, N10-Methylene-FH4 provides methyl-generated FH2 can then be regenerated by the reduction enzyme of bihydrofolate.

Figure 8-14 dTMP generation

.