Disease relevance of Ak1

• Creatine kinase, myokinase, and acetylcholinesterase activities in muscle-forming primary cultures of mouse teratocarcinoma cells [1].
• However, under hypoxia AK1-deficient hearts, compared with the wild type, had a blunted AK-catalyzed phosphotransfer response, lowered intracellular ATP levels, increased P(i)/ATP ratio, and suppressed generation of adenosine [2].
• Murine erythroleukemia (MEL) cells deficient in cAMP-dependent protein kinase (A-kinase) activity are impaired in chemically induced differentiation (Pilz, R. B., Eigenthaler, M., and Boss, G. R. (1992) J. Biol. Chem. 267, 16161-16167) [3].
• The adenylate kinase activity in the B-cells was apparently not influenced by hyperglycemia since it was similar both in obese-hyperglycemic mice of different ages and in lean mice, although the blood sugar concentrations in such animals are much different [4].
• Photosensitization of mitochondrial adenosine-triphosphatase and adenylate kinase by hematoporphyrin derivative in vitro [5].

Psychiatry related information on Ak1

• We measured contractile function, oxygen consumption, and the mean response time of oxygen consumption to a step increase in heart rate [i.e., mitochondrial response time (t(mito))] in isolated Langendorff-perfused hearts from wild-type (n = 6), M/MtCK(-/-) (n = 6), and AK(-/-) (n = 4) mice [6].

High impact information on Ak1

• However, creatine kinase activity rises during myotube formation and then drops abnormally, and myokinase activity fails to increase appreciably [1].
• Malate dehydrogenase, adenylate kinase, and NADH oxidase showed similar levels of activity in tumor and midpregnant mammary gland mitochondria [7].
• The activities of several mitochondria-specific enzymes including cytochrome oxidase, adenylate kinase, nicotinamide adenine dinucleotide (NADH)-cytochrome c reductase, and NADH oxidase were similar in both cell types [8].
• Adenylate kinase 1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement [9].
• The BC3H1 cell line has been used widely as a model for studying regulation of muscle-related proteins, such as the acetylcholine receptor, myokinase, creatine kinase, and actin [10].

Chemical compound and disease context of Ak1

• Murine erythroleukemia cells rendered deficient in cAMP-dependent protein kinase (A-kinase) activity by gene transfection are severely impaired in hexamethylene bisacetamide (HMBA)-induced differentiation (Pilz, R. B., Eigenthaler, M., and Boss, G. R. (1992) J. Biol. Chem. 267, 16161-16167) [11].
• ADP effects on bleomycin-induced DNA repair synthesis and adenylate kinase activity in permeable mouse sarcoma cells [12].

Biological context of Ak1

• Ak1 mRNA was upregulated during late spermiogenesis, a time when the flagellum is being assembled [13].
• AK1 and AK2 in the flagellar accessory structures provide a mechanism to buffer the adenylate energy charge for sperm motility [13].
• Furthermore, every gat+ hybrid clone expressed murine AK-1, a marker previously assigned to chromosome 2 [14].
• Along with AK 1, creatine kinase (CK) provides a major pathway for regulation of nucleotide ratios and energy metabolism in muscles [15].
• The skeletal muscle L-type Ca2+ channel (Ca(V)1.1), which is responsible for initiating muscle contraction, is regulated by phosphorylation by cAMP-dependent protein kinase (PKA) in a voltage-dependent manner that requires direct physical association between the channel and the kinase mediated through A-kinase anchoring proteins (AKAPs) [16].

Anatomical context of Ak1

• AK1 was first seen in condensing spermatids and was associated with the outer microtubular doublets and outer dense fibers of sperm [13].
• Our results suggested that decreased AK 1 expression and activity might result in redistribution of energy flow through the alternative CK system, thus a compensatory potential might limit cellular energy failure in mdx skeletal muscle [15].
• Deletion of the adenylate kinase gene compromised nucleotide exchange at the channel site and impeded communication between mitochondria and K(ATP) channels, rendering cellular metabolic sensing defective [17].
• We also show enrichment of dual A-kinase anchoring protein 1 at the neuromuscular junction, suggesting that it could be responsible for RIalpha tethering at this site [18].
• Cutting edge: A-kinase anchor proteins are involved in maintaining resting T cells in an inactive state [19].

Associations of Ak1 with chemical compounds

• Impaired intracellular energetic communication in muscles from creatine kinase and adenylate kinase (M-CK/AK1) double knock-out mice [20].
• An analysis of actomyosin complexes in vitro demonstrated that one of the consequences of M-CK and AK1 deficiency is hampered phosphoryl delivery to the actomyosin ATPase, resulting in a loss of contractile performance [20].
• The goal of this study was to investigate the consequences of AK deficiency (-/-) on adenine nucleotide management and whole muscle function at high-energy demands [21].
• We found that AK1(-/-) muscle exhibited a diminished inosine 5'-monophosphate formation rate (14% of WT) and an inordinate accumulation of ADP ( approximately 1.5 mM) at the highest energy demands, compared with WT controls [21].
• Adenylate kinase 1 knockout mice have normal thiamine triphosphate levels [22].
• Adenosine treatment bypassed AK1 deficiency and restored post-ischemic flow to wild-type levels, achieving phenotype rescue [23].

Other interactions of Ak1

• These clones were used to localize murine Fpgs and Ak-1 to a region of this chromosome, namely 2 (cen leads to Cl) [14].
• Herein, we show that simultaneous disruption of the genes for the cytosolic M-CK- and AK1 isoenzymes compromises intracellular energetic communication and severely reduces the cellular capability to maintain total ATP turnover under muscle functional load [20].
• Enzymatic assays demonstrated that AK 1 activity was also decreased in mdx mice [15].
• Proteomic analysis of mdx skeletal muscle: Great reduction of adenylate kinase 1 expression and enzymatic activity [15].
• Moreover, in AK1(-/-) mice, fast-twitch gastrocnemius, but not slow-twitch soleus, had an increase in adenine nucleotide translocator (ANT) and mitochondrial creatine kinase protein, along with a doubling of the intermyofibrillar mitochondrial volume [24].

Analytical, diagnostic and therapeutic context of Ak1

• To define the mechanisms of this adaptive response, soleus and gastrocnemius muscles from AK1(-/-) mice were characterized by cDNA array profiling, Western blot and ultrastructural analysis [24].
• Gene mapping in Mus musculus by interspecific cell hybridization: assignment of the genes for tripeptidase-1 to chromosome 10, dipeptidase-2 to chromosome 18, acid phosphatase-1 to chromosome 12, and adenylate kinase-1 to chromosome 2 [25].
• ADP supported repair patch ligation after being converted into ATP by adenylate kinase in permeable cells [26].
• The sensitivity attained is more than required for assay of clinical fine needle biopsies and is quite satisfactory for detection and estimation of adenylate kinase contaminants in enzyme preparations [27].
• In membrane preparations of normal erythrocytes and of nonparasitized erythrocytes separated from parasitized erythrocytes by zonal centrifugation was no difference in specific activities of ATPase, adenylate kinase and acetylcholinesterase [28].

References