5 -Nucleotidase regulation

Sequencing of several archaeal genomes revealed the existence of genes with high sequence similarity to the ATPases of the eukaryotic 19S regulator. The deduced 50 kDa proteins have N-terminal coiled-coils, a hallmark of proteasomal AAA ATPases, and C-terminal AAA domains. The Methanococcus jannaschii protein was expressed in E. coli and purified as a 650 kD complex with nucleotidase activity. When mixed with proteasomes from Thermoplasma, degradation of substrate proteins was stimulated up to... 

The enzyme in the myocardium has recently attracted attention because of the possibility that adenosine is a physiological regulator of coronary blood flow (67) (adenosine is a potent coronary dilator). Most of the 5 -nucleotidase activity in rat heart is membrane bound, and a partially purified preparation has been obtained by extracting acetone powder preparations with deoxycholate (68). All 5 -nucleotides are hydrolyzed. The enzyme is strongly inhibited competitively by ATP (Ki 1.8 fxM). Whether this provides a regulatory mechanism for adenosine formation in the heart is not known. 

Synnestvedt K, Furuta GT, Comerford KM, Louis N, Karhausen J, Eltzschig HK, Hansen KR, Thompson LF, Colgan SP (2002) Ecto-5 -nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. J Clin Invest 110(7) 993-1002... 

The accumulation of adenosine in hypoxia is at least partially explained by hypoxia-mediated regulation of enzymes that are involved in adenosine metabolism (i) adenosine kinase (Decking et al. 1997) and (ii) 5 -nucleotidase (Headrick and Willis 1989 Kobayashi et al. 2000 Thompson et al. 2004). In particular, adenosine can be generated extracellularly through the hydrolysis of released nucleotides by ecto-5 -nucleotidases (Dunwiddie et al. 1997) or can be produced in the cytosol and transported to the extracellular space (Higgins et al. 1994). 

Fig. 4 Mechanisms involved in the extracellular inactivation of nucleotides (a, b and c) and adenosine (d) and their influence on purine concentration in the P2Y and PI receptor biophases, (a) NT-PDasel hydrolyses ATP and ADP very efficiently, thus preventing their action on P2Y receptors (b) NTPDase2 metabolizes ATP preferentially, allowing an accumulation of ADP and thus favouring activation of P2Yi, 12,13 receptors (c) NTPDase3 hydrolyses both ATP and ADP slowly, giving them time to activate both P2Y2,4 and P2Y 1,12,13 receptors. Formation of adenosine depends on the activity of ecto 5 -nucleotidase (CD73). Adenosine inactivation systems also influence adenosine concentration in the PI receptor biophase (d) the nucleoside transporters take up adenosine adenosine deaminase (ADA) regulates both the concentration of adenosine in the Ai receptor biophase and the functionality of Ai receptors.

Lowenstein, JM, Yu, MK, Naito, Y, Regulation of adenosine metabolism by S -nucleotidase, In Regulatory functions of adenosine, (eds. Berne, RM., Rail, TW and Rubio, R), Martinus Nijhoff Publishers, The Hague, 1983, 117-131. 

Gottlieb, M. (1985) Enzyme regulation in a trypanosomatid effect of purine starvation on levels of 3 -nucleotidase activity. Science 111 72 74. 

The various APS and PAPS hydrolases described in Secticm III could be of some significance in the regulation of sulfate assimilation. However, since the synthesis of APS and PAPS are known to occur in chloroplasts, these possibilities must remain speculative until the subcellular localization of the enzymes catalyzing Eqs. (4)-(6) are established especially since Burnell and Anderson (1973a) reported that nonspecific 3 -nucleotidase is not associated with chloroplasts. Recently, Sawhney and Nicholas (1976b) have reported that particulate fractions from Anabaena degrade PAPS to sulfate. ADP sul-furylase, which catalyzes the reaction... 

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