ATP/ITP metabolism
ATP/ITP metabolism
ATP plays the important role in a metabolism. This compound is a universalenergy source for all biochemical processes occurring in live systems. Knowledge ofInosine metabolism has led to advances in immunotherapy inrecent decades.
ATP is often used as a phosphate source, e.g., in the reaction with Neopterindiphosphate ( NDP ) that results in formation of ADP andNeopterin-3'-triphosphate ( NTP ), as well as in the reaction with Inosinediphosphate ( IDP ) in which Inosine triphosphate ( ITP ) is formed. Thesereactions are catalyzed by similar enzymes, Nucleoside diphosphate kinase ( NDPKcomplex) [1], [2], [3], [4], [5], Non-metastatic cells 4, protein expressed in ( NDPK D (mitochondrial) )[6], [7], [8], Non-metastatic cells 3, proteinexpressed in ( NDPK C ) [9], [10], [7],Nucleoside non-metastatic cells 6, protein expressed in (nucleoside-diphosphate kinase) (NDPK 6 ) [11], [8], Non-metastatic cells 7, proteinexpressed in (nucleoside-diphosphate kinase) ( NDPK 7 ) [8] andnon-metastatic cells 2, protein (NM23B) expressed in, pseudogene 1 ( NDPK 8 )[12].
Hydrolysis of ATP to ADP proceeds in two ways and catalyzed by specificgroups of enzymes. The first group consists of Ectonucleoside triphosphatediphosphohydrolase 2 ( ENTPD2-alpha ) [13], [14],Ectonucleoside triphosphate diphosphohydrolase 1 ( ENP1 ) [15], [16], [17], [18], Ectonucleoside triphosphatediphosphohydrolase 3 ( ENP3 ) [19], [20], [21],Acylphosphatase 1, erythrocyte (common) type ( ACYP1 ) [22], [23], Acylphosphatase 2, muscle type ( ACYP2 ) [22], [23], Acid phosphatase 5, tartrate resistant ( PPA5 ) [24],[25], Epoxide hydrolase 2, cytoplasmic ( EPHX2 ) [26], andAlkaline phosphatase, placental (Regan isozyme) ( ALPP ) [26]. Thesecond group consists of Acid phosphatase 2, lysosomal ( PPAL ) [27],[28], [29], Acid phosphatase 5, tartrate resistant ( PPA5 )[30], [31], [32], [33], and Acid phosphatase,prostate ( PPAP ) [34], [35], [36], [37]. Second group also catalyzes further hydrolysis of ADP to AMP andAMP to release Adenosine.
There are two processes that lead to ITP hydrolysis. The first is a reactioncatalyzed by Ectonucleoside triphosphate diphosphohydrolase 1 ( ENP1 ) [15], [19], [18], Ectonucleoside triphosphatediphosphohydrolase 3 ( ENP3 ) [19], [20], [21],and Ectonucleoside triphosphate diphosphohydrolase 6 (putative function) ( ENTPD6) [38], [39]. It results in formation of IDP. Theseenzymes also participate in the following hydrolysis of IDP to Inosinemonophosphate ( IMP). And in the second case ITP is hydrolyzed directly toIMP by the action Inosine triphosphatase (nucleoside triphosphate pyrophosphatase)( ITPA ) [40], [41], [42], [43].
Yet another process leading to formation of ADP is the reaction of ATPwith AMP catalyzed by Adenylate kinase 5 ( AK5 ) [44],Adenylate kinase 1 ( AK1 ) [45], [44], Adenylate kinase 2 (AK2 ) [45], [44], Adenylate kinase 3-like 1 ( AK3 )[46], [44], TAF9 RNA polymerase II, TATA box binding protein(TBP)-associated factor, 32kDa ( KAD6 ) [47], [48], andAdenylate kinase 7 ( KAD7 ) [49], [50].
ADP can participate in reaction of formation of 2 '-deoxy-ADP ( dADP ). Thisreaction is catalyzed by Ribonucleotide reductase. This enzyme is involved in onemore reaction of formation of 2 '-deoxy-IDP ( dIDP ) from IDP [51], [52], [53], [54], [55]. dADPand dIDP take part in the dATP/dITP metabolism.
AMP can be hydrolyzed to IMP via two pathways. The first is a directhydrolysis catalyzed by AMP deaminase [56], [57], Adenosinemonophosphate deaminase 2 (isoform L) AMP deaminase 2 [58], [59], [60], Adenosine monophosphate deaminase 1 (isoform M) AMPdeaminase 1 [61], [62], [63], [64], andAdenosine monophosphate deaminase (isoform E) ( AMD3 ) [65], [66], [67], [68]. The second is represented by a chain ofconsecutive reactions: formation of Adenylo-succinate catalyzed byAdenylosuccinate lyase ( ADSL ) [69], [70], [71],[72], [73] followed by formation of IMP in the presenceof Adenylosuccinate synthase ( ADSS ) [74], [75], [76], [77] and Adenylosuccinate synthase like 1 ( ADSSL1 ) [74], [75], [76], [77], [78].IMP also takes part in IMP biosynthesis and GTP-XTP metabolism.
AMP can directly form Adenine, this reaction occurs in the presence ofAdenine phosphoribosyltransferase ( APRT ) [79], [80],[81]. Similar reaction proceeds for IMP from Hypoxanthine underthe action of Hypoxanthine phosphoribosyltransferase 1 ( HPRT ) [82],[83], [84], [85], [86]. Adenine andHypoxanthine participate in other processes, e.g., dATP/dITP metabolism and inGTP-XTP metabolism.
Nucleoside phosphorylase ( PNPH ) catalyzes the formation of Adeninefrom Adenosine [87], [88], [89] andInosine from Hypoxanthine [90], [91], [92], [87], [88], [89]. Inosine can also beproduced as a result of hydrolysis of Adenosine by Adenosine deaminase (ADA ) [93], [94], [95], Adenosine deaminase,RNA-specific ( ADAR1 ) [96], Adenosine deaminase, RNA-specific, B1(RED1 homolog rat) ( ADAR2 ) [96] Adenosine deaminase, RNA-specific,B2 (RED2 homolog rat) ( ADAR3 ) [96].
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