Last and not least, nucleotides are the monomeric units of nucleic acids.
Step 2 (Figure 27.3) is catalyzed by glutamine phosphoribosyl pyrophosphate amidotransferase.
The anomeric carbon of the substrate PRPP is in the a-configuration; the product is a b-glycoside (recall that all the biologically important nucleotides are b-glycosides).
Without RNA, protein biosynthesis is not possible; in the absence of DNA synthesis, the genetic material is not replicated and cell division cannot occur.
Nearly all organisms can make the purine and pyrimidine nucleotides via so-called de novo biosynthetic pathways.
The two major purine nucleoside diphosphates, ADP and GDP, are negative effectors of ribose-5-phosphate pyrophosphokinase.
However, because PRPP serves additional metabolic needs, the next reaction is actually the committed step in the pathway.By tracing the metabolic source of the various atoms in this end product, he showed that the nine atoms of the purine ring system (Figure 27.2) are contributed by aspartic acid (N-1), glutamine (N-3 and N-9), glycine (C-4, C-5, and N-7), CO The de novo pathway for purine synthesis.The first purine product of this pathway, IMP (inosinic acid or inosine monophosphate), serves as a precursor to AMP and GMP.The N atom of this N-glycoside becomes N-9 of the nine-membered purine ring; it is the first atom added in the construction of this ring.Glutamine phosphoribosyl pyrophosphate amidotransferase is subject to feedback inhibition by GMP, GDP, and GTP as well as AMP, ADP, and ATP.Nucleotides also act in metabolic regulation, as in the response of key enzymes of intermediary metabolism to the relative concentrations of AMP, ADP, and ATP (PFK is a prime example here; see also Chapter 19).Further, cyclic derivatives of purine nucleotides, c AMP and c GMP, have no other role in metabolism than regulation.In Step 1, ribose-5-phosphate is activated via the direct transfer of a pyrophosphoryl group from ATP to C-1 of the ribose, yielding 5-phosphoribosyl-a-pyrophosphate (PRPP) (Figure 27.3).The enzyme is ribose-5-phosphate pyrophosphokinase. PRPP is the limiting substance in purine biosynthesis.In Chapter 33, we will see that GTP serves as the immediate energy source driving the endergonic reactions of protein synthesis.Many of the coenzymes (such as coenzyme A, NAD, NADP, and FAD) are derivatives of nucleotides.