Disease relevance of AK1

• Red cell adenylate kinase deficiency associated with hereditary nonspherocytic hemolytic anemia: clinical and biochemical studies [1].
• We report here a case of red cell adenylate kinase (AK) deficiency associated with hereditary hemolytic anemia [1].
• Both the cDNA sequences were found to direct the active adenylate kinase synthesis in E. coli [2].
• Regional assignment of the loci for adenylate kinase to 9q32 and for alpha 1-acid glycoprotein to 9q31-q32. A locus for Goltz syndrome in region 9q32-qter [3]?
• The results strongly suggest that the locus determining AK1, 'red cell' adenylate kinase, is on chromosome 9 in man, and hence that the locus for the ABO blood groups and that for the Nail-patella syndrome may also be assigned to this chromosome [4].

Psychiatry related information on AK1

• No association of red cell adenylate kinase phenotypes with affective disorders [5].
• Two siblings of Italian origin with mild chronic haemolytic anaemia, psychomotor impairment and undetectable adenylate kinase (AK) activity are reported [6].
• There was a correlation between cerebrospinal fluid levels of adenylate kinase and psychometric test results as well as between the marker levels and clinical signs [7].
• No differences between normal pressure hydrocephalus, multiinfarct dementia and dementia of the Alzheimer type could be found with regard to adenylate kinase activity in CSF [8].

High impact information on AK1

• Phosphorylation of the glycogen-binding subunit of PP-1G by A-kinase promotes translocation of the catalytic subunit from glycogen particles to cytosol in skeletal muscle, inhibiting the dephosphorylation of glycogen-metabolizing enzymes [9].
• We found that CFTR also has adenylate kinase activity (ATP + AMP <=> ADP + ADP) that regulates gating [10].
• An intrinsic adenylate kinase activity regulates gating of the ABC transporter CFTR [10].
• Thus, channel activity could be regulated by two different enzymatic reactions, ATPase and adenylate kinase, that share a common ATP binding site in the second nucleotide binding domain [10].
• In eukaryotic cells, most cAMP-inducible genes so far studied are activated by the cAMP-dependent protein kinase (A kinase), which phosphorylates transcription factors that bind the cAMP-responsive element TGACGTCA [11].

Chemical compound and disease context of AK1

• Among six genes whose induction by hypoxia was newly defined in this way, three were of known function, encoding the glucose transporter isoform 3 (Glut-3), adenylate kinase isoenzyme 3 (AK-3), and tissue factor, two were expressed sequence tags (ESTs), and one corresponded to a new sequence [12].
• For Glut-3 and AK-3, mutant (c4) cells showed almost complete loss of the inducible response to both hypoxia and desferrioxamine [12].
• Three principal enzyme defects are causally associated with hemolytic anemia: hyperactive adenosine deaminase and deficiencies of adenylate kinase and pyrimidine nucleotidase [13].
• Effects of ciprofloxacin, norfloxacin, and ofloxacin on in vitro adhesion and survival of Pseudomonas aeruginosa AK1 on urinary catheters [14].
• Pretreatment of urinary silicone latex catheters in vitro with 0.1 and 0.5 microgram of ciprofloxacin per ml for 1, 24, and 48 h significantly reduced the adhesion and survival of the clinical isolate Pseudomonas aeruginosa AK1 [14].

Biological context of AK1

• The AK1 gene frequency was found to be 0.9669 for Caucasians, 0.9813 for Negroes, 0.9779 for Hispanic persons, and 1.000 for Chinese [15].
• With respect to AK1 phenotypes, there were statistically significant differences between the Central European group on the one hand and the Yemenite and South European groups on the other (p less than 0.05), and with respect to ACP1--between the Middle Eastern and the Yemenite groups (p less than 0.01) [16].
• The comparisons of amino acid sequences and genomic structure of three isozymes revealed that a segment corresponding to either exon 5 of the AK2 gene or a part of exon 3 of the AK3 gene is missing in the AK1 gene [2].
• The results of mRNA analysis in various tissues using the AK1 cDNA indicated that the AK1 gene expression is regulated both tissue-specifically and developmentally at the transcriptional level [2].
• It is probable that AK4 acts on the specific mechanism of energy metabolism rather than control of the homeostasis of the ADP pool ubiquitously [17].

Anatomical context of AK1

• Western blot analysis of AK isozymes in human heart and skeletal muscle revealed that AK2 protein was found only in heart, whereas AK1 was detected in both tissues [18].
• The AK1 isoenzyme was partially purified from the cytosol fraction of bovine aortic smooth muscle and had an apparent Mr of 23.5 kilodaltons [19].
• AK1 is localized in neuronal processes, sperm tail and on the cytoskeleton in cardiac cells at high concentrations, suggesting its regulatory function as a high-energy beta-phosphoryl transfer chain from ATP-synthesizing sites to the ATP-utilizing sites in the cell [20].
• AK4 mRNA is expressed in the mammalian central nervous system in a region-specific manner from the middle stage of embryogenesis to the adulthood in the rodent [17].
• The subcellular compartmentalization of the isoenzymes of ATP:AMP phosphotransferase (adenylate kinase) was analyzed in HeLa cells, RAG cells, and RAG-human hybrids that express human AK-2 [21].

Associations of AK1 with chemical compounds

• Phylogenetic analysis suggested that AK1, a shorter molecule, would have been separated from a longer molecule very early in evolution of adenylate kinase.(ABSTRACT TRUNCATED AT 400 WORDS)[2]
• In contrast to all other AK isoforms, AMP and dAMP were the preferred substrates of ADLP; CMP, TMP and shikimate acid were also good substrates [22].
• Enzymatic characterization by hemolysate revealed that the patient's AK had an increased Michaelis constant for adenosine diphosphate and slight thermal instability [1].
• Adenylate kinase is an ubiquitous enzyme which contributes to homeostasis of adenine nucleotide composition in the cell [2].
• The residual activity was not inhibited by N-ethylmaleimide, which completely abolishes the activity of the normal AK1 isozyme of erythrocytes [23].

Physical interactions of AK1

• Inhibition of ATPase, GTPase and adenylate kinase activities of the second nucleotide-binding fold of the cystic fibrosis transmembrane conductance regulator by genistein [24].
• Furthermore, in Glc+ mitochondria, the adenylate kinase reaction appears to be an important source of endogenous ATP for bound hexokinase, while, in Glc- mitochondria, hexokinase activity is almost totally dependent on the ATP generated by oxidative phosphorylation [25].

Regulatory relationships of AK1

• In addition, AK-1 was found to be expressed independently of AK-2 [26].
• We hypothesize that during periods of high energy demand, exclusively AMP deaminase is activated as a means (1) to push the myokinase reaction toward ATP synthesis, (2) to supply allosteric effectors, and (3) to remove some of the accumulating protons through the formation of ammonium, all at the expense of the adenylate pool [27].

Other interactions of AK1

• Subcellular localization studies showed a predominant nuclear localization for this protein, which is different from AK1-AK5, but similar to that of human AK6 [22].
• Cloning and expression of human adenylate kinase 2 isozymes: differential expression of adenylate kinase 1 and 2 in human muscle tissues [18].
• The gene frequencies observed are: PGM1/1: 0.715, AK1: 0.962 AND ADA1: 0.940 [28].
• The ADA, PGM and AK enzymes were found to be polymorphic in the Turkish population [29].
• The interpopulation heterogeneity test shows a high level of genetic differentiation in the following loci: HP, GC, ESD, AK1, TF, PGD [30].

Analytical, diagnostic and therapeutic context of AK1

• The patient's enzyme migrated approximately half-way between the AK 1 and AK 2 position on starch-gel electrophoresis [1].
• The adenylate kinase zymograms obtained from isoelectric focusing yielded two typical isoform patterns: (1) with a pI greater than or equal to 9 and 8.6, specific for bovine skeletal muscle, heart, aorta and brain, and (2) with a pI = 7.9 and 7.1, specific for liver and kidney [19].
• The subsequent sequence analysis of this abnormal fragment revealed homozygous and heterozygous A-->G substitutions in the proband and in the parents and brother respectively at codon 164, corresponding to a tyrosine-->cysteine substitution in the AK protein [31].
• On reperfusion, AK1 knockout hearts demonstrated reduced nucleotide salvage, resulting in lower ATP, GTP, ADP, and GDP levels and an altered metabolic steady state associated with diminished ATP-to-P(i) and creatine phosphate-to-P(i) ratios [32].
• We also used Southern blot analysis and a radiation hybrid cell line, E6B, to exclude 3 genes--PBX3A, RXR alpha, and TAN1--from the AK1 to D9S114 interval [33].

References