Lecture 31 Summary

Nucleotide metabolism: Introduction and overview.

The nucleotides occupy a prominent place in living cells. Their triphosphate forms are activated precursors of DNA and RNA. ATP is the main energy currency of the cell. Adenine nucleotides are found in many important cofactors, such as NAD+, FAD, coenzyme A, and S-adenosylmethionine (SAM). Cyclic nucleotides - primarily cAMP - act in signal transduction pathways. Guanine nucleotides also have energetic and signaling roles. UDP-glucose provides another example of nucleotides as carriers of high transfer potential biosynthetic units.

Biosynthetic pathways for nucleotides are of two classes: de novo and salvage. The de novo pathways build up the purine or pyrimidine rings of the bases from precursors and group donors. The salvage pathways utilize pre-existing bases and form N-glycosyl linkages with phosphoribose. A key metabolite is 5-phosphoribosyl-1-pyrophosphate (PRPP), which is activated for transfer of ribose 5-phosphate to a nitrogen nucleophile. PRPP participates in both de novo and salvage pathways.

Nucleotide biosynthesis is mainly regulated by feedback inhibition. For example, the first committed step in de novo pyrimidine biosynthesis is catalyzed by aspartate transcarbamoylase (ATCase). Recall that ATCase from E. coli is allosterically inhibited by one of the products of this pathway, cytidine triphosphate (CTP).

Carbamoyl phosphate synthetase (type II): Structure, function, channeling of intermediates

Continuation of pyrimidine biosynthetic pathway.

Study questions

• .

Page updated 12-27-06

References

1. Berg, Tymoczko, and Stryer. Biochemistry (BTS): 6th edition (2007, Freeman) Ch.25, pp.709-714.