* Note: We will soon see other important purines and pyrimidines.

(5) The same "channeling" phenomenon is seen in the pyrimidinepathway that we saw in the purine pathway. The enzymes in steps 1,2 and 3 are onthe same polypeptide chain, while the last two (reactions 5 and 6) are onanother single chain.

 Purinesbond to the C1' of the sugar at their N9 atoms

Finally, in this pathway, many of the enzymes are grouped together on singlepolypeptide chains. This serves to organize and control the processing of asubstrate from one step to the next. Such "chanelling" increases theoverall rate of a pathway and protects intermediates from degradation. Inanimals, the enzymes of the IMP synthesis pathway are grouped as follows:

[1] PRPP Synthetase (see "Purine Lecture")

A "nucleotide" is a 5'-phosphate ester of a nucleoside.

What's really interesting here is that the ribose sugar is recycled in theform of ribose-1-phosphate, which can be incorporated into PRPP which, as we nowknow, is integral to the biosynthesis of purines, pyrimidines, histidine andtryptophan. That's a really efficient way to run a cell!

The major site of purine synthesis is in the liver

What this shows is that the overall effect of combining these two reactionsis a net result of deaminating an aspartate to a fumarate at the expense of aGTP molecule. This cycle of reactions is know as the and it is ofphysiologic importance in muscle metabolism. Muscle tissue replenishes itscitric acid cycle intermediates via the purine nucleotide cycle rather thanthrough the usual "replenishing reactions", the most important ofwhich is the generation of oxaloacetate from pyruvate catalyzed by pyruvatecarboxylase. The fumarate generated in the purine nucleotide cycle feeds intothe citric acid cycle to regenerate malate, oxaloacetate, and so forth.

Folate-Dependent Purine Nucleotide Biosynthesis in …

Women are already advised to take folic acid supplements, a synthetic compound of folate, before conceiving and during the early months of pregnancy, to reduce the risk of defects such as spina bifida, a defect of the spinal column.

| Purine nucleotide biosynthesis ..

The nucleosides inosine, xanthosine and guanosine are degraded respectivelyto hypoxanthine, xanthine and guanine and, in the process, the ribose sugar,which was attached by its C1 to the base is phosphorylated:

Folate-Dependent Purine Nucleotide Biosynthesis in Humans

Although we haven't yet shown how to get deoxyribonucleotides fromribonucleotides, whatever we say about the purine ribonucleotide degradationpathways will hold for the purine deoxyribonucleotides.

that folate factors into purine synthesis.

Specific nucleotidases and nonspecific phosphatases further degradenucleotides to nucleosides. These can either be absorbed into intestinal mucosaor degraded in the intestine by nucleosidases and nucleoside phosphorylases Asfollows: