Uridylate kinase

Adenylate kinase performs the essential function of recovering AMP formed by many enzymatic processes and converting it to ADP (Eq. 6-65) which can be reconverted to ATP by oxidative or substrate level phosphorylation. The enzyme is present in all organisms. In vertebrates different isoenzymes function in the cytosol, mitochondrial intermembrane space, and mitochondrial matrix.862 863 A group of other nucleotide and deoxynucleotide kinases convert nucleoside monophosphates into diphosphates.864 865 Some of them, e.g., uridylate kinase are similar in structure and properties to adenylate kinase.866 867 Another member of the adenylate kinase family is phosphoribulokinase, an important photosynthetic enzyme (see Fig. 17-14, step a).868... 

Uridylate kinase 655 5 -Uridylic acid. See UMP Urocanase reaction 778 Urocanic acid 755,756s Urokinase 634 Uronic acid 164 Uroporphyrin(s) 843 Uroporphyrin I, 845s Urothione 804s, 891 Urticaria 385 Usher protein 364... 

Figure 14.3 Superposed X-ray structures of estrogen sulfo-transferase, uridylate kinase, and their cofactors and substrates.

Estrogen sulfotransferase green with consumed cofactor (PAP) and substrate (17(3-estradiol) in yellow uridylate kinase blue with consumed cofactor (ADP) and substrate analog (ADP) in red. 

H.J. Muller-Dieckmann and G.E. Schulz. 1994. The structure of uridylate kinase with its substrates, showing the transition state geometry J. Mol. Biol. 236 361-367. (PubMed)... 

UMP is converted to UTP by uridylate kinase and nucleoside diphosphate kinase. 

GxxGxxKT P-loop Ras-p21-GTPase, PEP carboxykinase, uridylate kinase P-loops occur in many doubly wound O/p structures. This motif functions by binding the phosphate backbone of a mononucleotide. 

Thus, while existence of a cytidylate-deoxycytidylate kinase is established, there remains some uncertainty about the association of uridylate kinase activity with this enzyme. Phosphorylation of deoxyuridylate appears to be catalyzed by a separate enzyme activity, possibly by thymidylate kinase. 

GTP AMP phosphotransferase GTP-adenylate kinase U ridylate-cytidy late kinase Uridylate kinase Cytidylate-deoxy-c)rtidylate kinase... 

As a further instance of a dual function for the nucleoside monophosphate kinases, separate kinases for adenylate-deoxyadenylate, guanylate-deoxyguanylate, cytidylate-deoxycytidylate, uridylate, and thynudylate have been demonstrated in E. cdi extracts (35) it should be noted that cytidylate-deoxycytidylate kinase and uridylate kinase were found as separate enzyme activities in the E. cdi experiments. 

Enzymes, measured in clinical laboratories, for which kits are available include y-glutamyl transferase (GGT), alanine transferase [9000-86-6] (ALT), aldolase, a-amylase [9000-90-2] aspartate aminotransferase [9000-97-9], creatine kinase and its isoenzymes, galactose-l-phosphate uridyl transferase, Hpase, malate dehydrogenase [9001 -64-3], 5 -nucleotidase, phosphohexose isomerase, and pymvate kinase [9001-59-6]. One example is the measurement of aspartate aminotransferase, where the reaction is followed by monitoring the loss of NADH ... 

Scheme 4.23 The use of glycosyl transferases in combination with in situ co-factor regeneration. E —galactosyl tranferase E2 — pyruvate kinase E3 = UDP-Glc-pyrophosphorylase E4 = galactose-1-phosphate uridyl transferase E5 = galactokinase.

In a preparation from calf liver, Strominger et al. 13) achieved a partial separation of uridylate-cytidylate kinase activity from those for guanylate... 

Sugino el al. 17) have partly purified a deoxycytidylate kinase from calf thymus this preparation also phosphorylates cytidylate and uridylate, but not deoxyuridylate. The deoxyuridylate kinase activity was recovered in another protein fraction and so represents a distinct entity. As phosphate donors, only ATP and dATP were active in the cytidylate reaction. 

Nelson and Carter 18) have purified thymidylate kinase about 5,000-fold from E. coli B and have shown that thymidylate was phosphorylated about seven times faster than deoxyuridylate. Uridylate was not a substrate, nor were adenylate, guanylate, cytidylate, or their deoxyribosyl counterparts. This enzyme was less specific for the triphosphate phosphoryl donor than the kinases previously discussed, because CTP, GTP, and the corresponding deoxyribonucleotides also served as phosphate donors, although less weU than ATP. 

More recently, Reyes (19) has shown that ceU-free extracts from cells of a transplantable rodent leukemia catalyze the PP-ribose-P-dependent synthesis of uridylate and 5-fluorouridylate the enzyme involved, apparently a phosphoribosyltransferase, was virtually absent from a line of 5-fluoro-uracil-resistant mouse leukemia L1210 cells. Because of their ability to grow without this enzyme, the resistant cells must have obtained their pyrimidine nucleotide requirements by an alternate means, possibly by the phosphorylase-kinase route (reactions 5 and 6, Fig. 12-1), or by the de novo pathway. 

Fractionation of extracts from calf thymus for kinase activity toward deoxyribonucleoside monophosphates has revealed the presence of at least four separate enzymes the kinase activities for dAMP, dGMP, dCMP, and dTMP are separate entities in this tissue 31). Each has been partly purified and examination of substrate specificities showed that the kinases for deoxyadenylate and deoxyguanylate also phosphorylate the ribosyl homologues, adenylate and guanylate, respectively. The deoxycytidylate kinase accepts as substrates both cytidylate and uridylate, but will not phosphor> late deoxyuridylate. The calf thymus thymidine monophosphate... 

UMP in a reaction that greatly resembles that of adenylate kinase. The reaction requires ATP and results in the formation of ADP and UDP. The complete purification of kinases of this type has not been achieved, but the partial separations already accomplished indicate that at least three, and possibly more enzymes with varying substrate specificities exist. These enzymes, studied in calf liver extracts, all use ATP as the phosphate donor, and show at least relative specificity for adenylic acid, uridylic acid, and cytidylic acid as phosphate acceptors. 

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