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Pathway · 8 proteins

Interconversion and salvage

Kinases and salvage enzymes rebalance usable nucleotide pools.

How it works

  1. Salvage enzymes recover free bases: hypoxanthine phosphoribosyltransferase and uracil phosphoribosyltransferase reuse hypoxanthine and uracil with PRPP, which costs less than making the ring again.
  2. Nucleotide kinases rebalance phosphate groups. Adenylate kinase, nucleoside-diphosphate kinase and CTP synthase (which aminates UTP using glutamine) keep the nucleoside triphosphate pools interconvertible.
  3. IMP dehydrogenase and GMP synthase route IMP toward GMP. The annotations show that the cell can interconvert and salvage these pools; which direction dominates depends on demand and is not fixed by the gene list.

Grouped by the atlas’s curated pathway map. The table order is not a proven reaction order.

Its proteins

ProteinECReaction (UniProt)Metal or clusterAmino acidsCertainty
Adenylate kinase2.7.4.3AMP + ATP = 2 ADP—206Step named
CTP synthase6.3.4.2UTP + L-glutamine + ATP + H2O = CTP + L-glutamate + ADP + phosphate + 2 H(+)Mg(2+)531Step named
Nucleoside diphosphate kinase2.7.4.6a 2'-deoxyribonucleoside 5'-diphosphate + ATP = a 2'-deoxyribonucleoside 5'-triphosphate + ADPMg(2+)142Step named
Guanylate kinase-like domain-containing protein———109System only
Inosine-5'-monophosphate dehydrogenase1.1.1.205IMP + NAD(+) + H2O = XMP + NADH + H(+)K(+)490Step named
Uracil phosphoribosyltransferase2.4.2.9UMP + diphosphate = 5-phospho-alpha-D-ribose 1-diphosphate + uracil5-phospho-alpha-D-ribose 1-diphosphate, Mg(2+)208Step named
GMP synthase [glutamine-hydrolyzing]6.3.5.2XMP + L-glutamine + ATP + H2O = GMP + L-glutamate + AMP + diphosphate + 2 H(+)—510Step named
Hypoxanthine-guanine phosphoribosyltransferase2.4.2.8IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphateMg(2+)178Step named

Origins

How were nucleotides activated and recycled before the kinases and salvage enzymes that do it today?

Naturalistic proposal

Nucleosides can be phosphorylated in the laboratory by orthophosphate or trimetaphosphate. High concentrations of polyphosphate in volcanic condensates and steam vents suggest it could have been an early energy source.

Design analysis

Nucleotides are useful to the cell only as diphosphates and triphosphates, and kinases make these from monophosphates. Salvage enzymes put free bases back onto activated ribose, so nothing is wasted. Eight proteins in the minimal set serve this interconversion, and copying DNA or RNA has to wait for them.

From the books: Zubay, Origins of Life on Earth and in the Cosmos, p. 223; Nelson & Cox, Lehninger Principles of Biochemistry, p. 511.

The wider question for this part of the cell: origins for making dna and rna letters.

Sources

Other pathways in this group: Purine biosynthesis · Pyrimidine biosynthesis · Deoxyribonucleotide supply · Aromatic amino acids · Purine metabolism · Pyrimidine metabolism · Histidine metabolism · Not yet placed in a pathway