Adenylate kinase location

Kawai, M. Uchimiya, H. Biochemical properties of rice adenylate kinase and subcellular location in plant cells. Plant Mol. Biol., 27, 943-951 (1995)... 

It was found that the enzyme is specific for (/ )-ATPaS but does not react with (S)-ATPaS. As shown in Scheme 43, when (/ )-ATPatS and l70-acetate are used as substrates, the 170 from acetate will be incorporated into the pro-5 position of AMPS if the reaction proceeds with retention of configuration or into the pro-/ position if inversion occurs. To determine the configuration of the 170-labeled AMPS (compound type 4), it is converted to (S)-ATPoS by stereospecific phosphorylation at the pro-/ oxygen catalyzed by adenylate kinase, followed by a second phosphorylation catalyzed by pyruvate kinase (144,145). By such a conversion, 170 should be incorporated into the nonbridging position of (5)-ATPaS if the step of acetate activation proceeds with retention of configuration. On the other hand, 170 should be located at the P—O—P bridging... 

Sachsenheimer and Schulz report the structure of another crystalline form of adenylate kinase which appears to be related to the previously known form by a conformation change in a segment. The binding sites of ATP and AMP to this enzyme were also located. Similar work on the identification of binding sites and the assessment of conformational changes has been continued with ribo-nuclease, alcohol dehydrogenase, concanavalin A, " hexokinase, lysozyme," flavodoxin, and oxy-erythrocrurin." ... 

Recent studies on mitochondrial structure have demonstrated the localization of mitochondrial enzymes in two membranes and two potential spaces (Fig. 4). For a substrate to react with an enzyme located in the mitochondrial matrix, it must first penetrate both outer and inner membranes. The outer membrane does not appear to hinder the passage of small molecules and substrates. The inner mitochondrial membrane, more analogous to the lysosomal membrane, is relatively impermeable to small molecules and ions (Chappell and Crofts, 1966). For anionic substrates to reach the matrix dehydrogenases, specific transporting systems are present in the inner mitochondrial membrane. Even for diose enzymes located in the inner membrane, penetration of that structure must occur as the active center of such enzymes is only available from the matrix side of the membrane (Chappell, 1968). Such data demonstrate that the presence of a membrane does not in itself induce enzyme latency as creatinine kinase and adenylate kinase localized in the intermembrane space, do not show latency. Moreover, monoamine oxidase and NADH cytochrome c reductase, present in the outer mitochondrial membrane, do not show latency. 

In humans the intronless gene encoding HR2 is located on chromosome 5. The human HR2 is a protein of 359 amino acids coupled to both adenylate cyclase and phosphoinositide second messenger systems by separate GTP-dependent mechanisms including Ga and also induces activation of c-Fos, c-Jun PKC and p70S6 kinase [16], Studies in different species and several human cells demonstrated that inhibition of characteristic features of the cells by primarily cAMP formation dominates in HR2-dependent effects of histamine. 

IP3 and DAG are derived from the membrane lipid phosphatidylinositol 4,5-bisphosphate (which is a phosphorylated derivative of phosphatidylinositol see Topic El) by the action of phospholipase C which is also located in the plasma membrane and, like adenylate cyclase, is activated by G proteins (Fig. 5). One of the main actions of the polar IP3 is to diffuse through the cytosol and interact with Ca2+ channels in the membrane of the ER (Fig. 5), causing the release of stored Ca2+ ions which in turn mediate various cellular responses. The DAG produced by the hydrolysis of phosphatidylinositol 4,5-bisphosphate, along with Ca2+ ions released from the ER, activates protein kinase C, a membrane-bound enzyme that phosphorylates various target proteins, again leading to alterations in a variety of cellular processes (Fig. 5). 

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