Adenosine kinase deficiency
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Adenosine kinase (ADK) deficiency was first described in 2011, the result of an exome sequencing study in six patients from three families with global retardation, epilepsy, hepatic dysfunction, dysmorphic features and hypermethioninemia [1]. Increased urinary concentration of adenosine was considered to confirm the diagnosis. Since then, eleven additional patients from eight families were published [2], and one report of a family (three girls) with previously undetermined hypermethioninemia [3] could be assigned as ADK deficiency [2], so in total 20 patients have been published. All patients share the clinical features of psychomotor retardation, muscular hypotonia, and frontal bossing. All but one family presented with hepatic disease and most patients developed severe epilepsy in infancy.
Composition of The Chromaffin Cell
Stephen W. Carmichael, Susan L. Stoddard in The Adrenal Medulla 1986 - 1988, 2017
The subcellular distribution of diadenosine tetraphosphate and diadenosine pentaphosphate was studied by Rodriguez del Castillo, Torres, Delicado et al. (1988). In bovine adrenal medullary tissue, these diadenosine polyphosphates were most concentrated within chromaffin vesicles. Enzymatic degradation with phosphodiesterase produced AMP as the final product. The diadenosine polyphosphates were potent inhibitors of adenosine kinase.
THE RED BLOOD CELL
David M. Gibson, Robert A. Harris in Metabolic Regulation in Mammals, 2001
tn the red Wood сея under normal homeostatic conditions (An ww» the concentrations ol the adenine nucleotides are ATP - 2.0 mM. ADP 0 t mM and AMP - 0 04 mM The ratios among these are principally due to the balance between metabcAc demand lor al AlP dependent processes and the coupled gtyedyte ttux (Section 5 4) that rephosphoryiates released ADP to ATP The relative amount ot amp e He equilibration of ATP and ADP m the reversiBe aderbate kinase reaction ATP - AMP - = 2 ADP The steady state ratio ot ATP to ADP plus AMP is kept high л order to promote the endergone restorative and synthetic lunctions that permit the continued enstence ot the cellular dissipative system (Chapter 1(The concentrabon ol ATP also depends on the size ol the coUectr»« adenine nucleotide pod (ATP • ADP • AMPi The post size is the steady-state balance between its rate ol synthesis trom precursors (an ender gon к ATP-dependent muttienzyme pathway) and the rate of degradaben iän exergonic multienzyme pathway! As the diagram indícales there is a flux ot organe ntermeâales entering and teawng the ceu. the magnitude of which is controlled by the quantity ot specifc. coupled enzymes, their affinity tor substrates and the presence ot ATP ATP thus sustains the steady-state level of the adenne nucieobdes and this syntnetc llux »ke all others, contributes to the magnitude ot the metabolic demand The structure of the adenne nucieobdes. precursors and products are shown in the margin, page 110 The pnncpal flows and the enzymes are rfentitied by nunber in AMP-ase. (2) adenosne deamnase; (3) adenosine kinase. |4) adenylate tonase. (5) AMP deaminase. (6) IMP ase; (7) purine nucleoside Phosphorylase |8i phosphoribo pyrophophate iPRPPi synthetase. 19) adenine phosphorfcosyt transferase (ADPflT), (10) hypoxanthine-guanine phoephonöosyl transferase (HGPRTl. The letters stand lor: (I) nput. (Ot output |G) glycolysis (Figue 5.2|; (PPP) pentose phosphate pathway (Figure 5.8): (MOl metabolic demand: (R5P| nbose-S-phosphate. (RIP) ribose-1-phosphate |PR°Pi phosphoribo pyrophosphate and (PP) notganc pyrophosphate
Approaches for designing and discovering purinergic drugs for gastrointestinal diseases
Published in Expert Opinion on Drug Discovery, 2020
Diego Dal Ben, Luca Antonioli, Catia Lambertucci, Andrea Spinaci, Matteo Fornai, Vanessa D’Antongiovanni, Carolina Pellegrini, Corrado Blandizzi, Rosaria Volpini
In parallel, under physiological conditions, the levels of purines are finely tuned also by the activity of the nucleoside transporters [47]. Nowadays, these transporters are classified as: (a) equilibrative nucleoside transporters (ENTs), designated as ENT1, ENT2, ENT3, and ENT4, which transport nucleosides across cell membranes in either directions, based on concentration gradients; (b) concentrative nucleoside transporters (CNTs), classified in CNT1, CNT2, and CNT3, promoting the intracellular influx of nucleosides against their concentration gradient, using the sodium ion gradient across cellular membranes as a source of energy [48]. Once transported intracellularly, Ado gets phosphorylated to AMP by the intracellular adenosine kinase (ADK) enzyme, which controls the poly-phosphorylation of Ado to ATP. Intracellular Ado may also be converted to inosine by the intracellular ADA [39].
CD73 as a potential opportunity for cancer immunotherapy
Published in Expert Opinion on Therapeutic Targets, 2019
Ghasem Ghalamfarsa, Mohammad Hossein Kazemi, Sahar Raoofi Mohseni, Ali Masjedi, Mohammad Hojjat-Farsangi, Gholamreza Azizi, Mehdi Yousefi, Farhad Jadidi-Niaragh
The cooperative enzymatic function of CD39 and CD73 regulates purinergic signals through conversion of ATP/ADP/AMP to adenosine. This activity attenuates pro-inflammatory condition generated by ATP and converts it into an anti-inflammatory environment by adenosine. Regarding an important role of ATP metabolism in the physiologic processes and signaling and immune homeostasis, it is tightly regulated. While CD39 converts ATP into AMP with just trace levels of ADP, CD73 generates adenosine from AMP [68]. CD39 degrades ATP through phosphohydrolyzing in the presence of Ca2+ and Mg2+ to generate AMP [69]. Generation of AMP from ATP by CD39 is a reversible reaction by a function of two extracellular kinases including NDP kinase and adenylate kinase that facilitate the conversion of ADP to ATP and AMP to ADP, respectively. On the other hand, generation of adenosine from AMP by CD73 is irreversible. However, it can be reversible upon intracellular transport of adenosine via the action of adenosine kinase [52]. ATP and ADP are also competitive inhibitors of CD73 [70,71]. Therefore, it seems that CD73 is a key checkpoint in the metabolism of immune-stimulating ATP and its conversion into immune-regulatory adenosine.
Characteristics and the role of purinergic receptors in pathophysiology with focus on immune response
Published in International Reviews of Immunology, 2020
Marharyta Zyma, Rafał Pawliczak
Adenosine can regulate the innate immune system leading to prevention of inflammatory damage of tissue in patients with sepsis. Additionally, the adenosine kinase activity is inhibited, causing an increase of adenosine level [85]. Neutrophils have the ability to release AMP, arising the adenosine levels. This adenosine binds to A2A receptors on neutrophils and inhibits free radicals, cytokines, and leukotriene B4 production as well as adhesion molecules expression and increases the intracellular level of cAMP. On the other hand, binding of the adenosine to A1 receptors increases the inflammatory activity of neutrophils at sites with low concentration of adenosine [85]. Moreover, macrophages can express all adenosine receptors and have the ability to generate ATP leading to production of exogenous adenosine. This adenosine is able to inhibit the monocyte differentiation and, also, the macrophages phagocytic functions [85]. Furthermore, adenosine has the ability to boost the inflammatory activity of mast cells in human through the binding to A2A receptors in mast cells [85].
Related Knowledge Centers
- Adenosine
- Adenosine Monophosphate
- Enzyme
- Adenosine Triphosphate
- Adk