### Enzymes Involved in Nucleotide Metabolism  
In nature, nucleotides are synthesized through the de novo or the salvage pathway. The de novo synthesis of pyrimidine nucleotides begins with glutamine or aspartate and progresses through orotate and 5-phospho-D-ribosyl-\(\alpha\)-1-pyrophosph (PRPP), ultimately forming oroidine-5\({}^{\prime}\)-monophosphate. It is then decarboxylated to form uridine-5\({}^{\prime}\)-monophosphate (UMP), which is further converted into UDP, UTP, and other pyrimidine nucleotides, including those with cytosine or thymine bases [3]. In contrast to pyrimidine nucleoside synthesis, where the nucleobase is synthesized separately and then attached to an activated sugar, de novo purine nucleoside synthesis occurs directly on the ribose backbone. Starting with PRPP, an amide nitrogen is first added to the 1-position, followed by the stepwise construction of the purine nucleobase with the help of molecules such as glycine, glutamine, and aspartate [1]. The resulting inosine-5\({}^{\prime}\)-monophosphate (IMP) serves as a precursor for other purine nucleotides, including adenosine-5\({}^{\prime}\)-monophosphate (AMP), xanthosine-5\({}^{\prime}\)-monophosphate, and guanosine-5\({}^{\prime}\)-monophosphate (GMP), which are then further phosphorylated to form the respective 5\({}^{\prime}\)-NDPs and 5\({}^{\prime}\)-NTPs. Deoxyribonucleotides are generated by ribonucleotide reductase (RNR) from their ribose counterparts, primarily at the 5\({}^{\prime}\)-NDP level (Figure 1). Detailed reviews have summarized the enzymes involved in the de novo pathway [3]. Certain cell types and even entire organisms, such as many parasites, are incapable of performing the de novo synthesis, particularly of purine nucleotides [20]. Instead, they rely on the salvage pathway, where nucleobases and nucleosides from external sources or internal degradation are recycled to produce nucleotides, requiring less energy input. For nucleotide and nucleoside breakdown, various nucleosidases and phosphatases exist. An interesting example is the nucleosidase PpnN of _Escherichia coli_, which regulates purine homeostasis by cleaving 5\({}^{\prime}\)-NMPs [21]. Its activity is notably stimulated by the alarmones (p)ppGpp. Nucleosidases, nucleotides, and phosphatases are only included in this review in case they have also been shown to be active in the synthesis direction. Figure 1 provides an overview of the key enzymes responsible for the formation and interconversion of 5\({}^{\prime}\)-NMPs (Section 1.2.1), 5\({}^{\prime}\)-NDPs (Sections 1.2.2 and 1.2.4), and 5\({}^{\prime}\)-NTPs (Sections 1.2.3 and 1.2.4). These enzymes have also been applied in in vitro synthesis routes to produce valuable 5\({}^{\prime}\)-NTPs. The focus is on the substrate scope of the enzymes, with information on other aspects such as structure and kinetics being available elsewhere [22; 23]. Figure 1: Enzymes involved in the nucleotide salvage pathway. AD: adenine deaminase, ADA: adenosine deaminase, Ack: acetate kinase, AMPDA: AMP deaminase, 8-RFAS: 4-(D-ribofuranosyl)aminobenzenzen synthases, CD: cytosine deaminase, CDA: cytidine deaminase, CK: creatine kinase, CMPDA: CMP deaminase, CTP-S: CTP synthetase, (d)NK: (deoxy)nucleoside kinase, GD: guanine deaminase, GDA: guanosine deaminase, GMP-S: GMP synthase, IMPDH: IMP dehydrogenase, NDPK: NDP kinase, NH: nucleoside hydrolase, NMPK: NMP kinase, NP: nucleoside phosphorylase, NPT: nucleoside phosphotransferase, NSAP: nonspecific acid phosphatase, NT: 5\({}^{\prime}\)-nucleotidates, PDN2\({}^{\prime}\)H: pyrimidine nucleoside 2\({}^{\prime}\)-hydroxylase; PK: pyruvate kinase, PR: ribose-5\({}^{\prime}\)-phosphate, PPK: polyphosphate kinase, PRT: phosphoribosyl transferase, PRPP: 5-phospho-D-ribosyl-\(\alpha\)-1-pyrophosphate, PUS: pseudouridylate synthase; RNR: ribonucleotide reductase, TMP-S: thymidylate synthase.