Adenylate kinase mitochondrial enzyme

Adenylate kinase (AK) is a ubiquitous monomeric enzyme that catalyzes the interconversion of AMP, ADP, and ATP. This interconversion of the adenine nucleotides seems to be of particular importance in regulating the equilibrium of adenine nucleotides in tissues, especially in red blood cells. AK has three isozymes (AK 1,2, and 3). AK 1 is present in the cytosol of skeletal muscle, brain, and red blood cells, and AK 2 is found in the intermembrane space of mitochondria of liver, kidney, spleen, and heart. AK 3, also called GTP AMP phosphotransferase, exists in the mitochondrial matrix of liver and heart. 

Sus scrofa (acidic adenylate kinase from pig heart resembles liver mitochondrial enzyme [14]) [3, 13-16]... 

Adenylate kinase performs the essential function of recovering AMP formed by many enzymatic processes and converting it to ADP (Eq. 6-65) which can be reconverted to ATP by oxidative or substrate level phosphorylation. The enzyme is present in all organisms. In vertebrates different isoenzymes function in the cytosol, mitochondrial intermembrane space, and mitochondrial matrix.862 863 A group of other nucleotide and deoxynucleotide kinases convert nucleoside monophosphates into diphosphates.864 865 Some of them, e.g., uridylate kinase are similar in structure and properties to adenylate kinase.866 867 Another member of the adenylate kinase family is phosphoribulokinase, an important photosynthetic enzyme (see Fig. 17-14, step a).868... 

In fact, kinetic studies of the GTP-dependent avian mitochondrial enzyme indicate two metal-binding sites, one on the polyphosphate group of the bound GTP and one on carboxylate side chains of the protein.252 255 The three-dimensional structure of the ATP-dependent E. coli enzyme reveals a nucleotide binding site similar to the ATP site of adenylate kinase (Fig. 12-30).256 A definite binding site for C02 is also present in the enzyme.257... 

A major function of the Bcl-2 family members is to regulate cytochrome c release via their interaction with the outer mitochondrial membrane. As described above, cytochrome c release is an important first step in initiating apoptotic events in cells because of its ability to interact with and thereby activate Apaf-1. However, mitochondria can also release a number of other proteins during apoptosis, such as AIF, certain procaspases, catabolic enzymes, adenylate kinase 2 and SMAC/Diablo. The role of these proteins in the apoptotic process is not known with certainty. Anti-apoptotic proteins of the Bcl-2 family possess membrane anchoring domains at their carboxy terminus that target the... 

Table 4-II shows the adenylate kinase activities of unfractionated soluble extracts of several rat tissues (5). The assay used was ADP synthesis from ATP and adenylate these data indicate that rat tissues differ widely in their adenylate kinase activities. The adenylate kinase activity of liver cells is also present in mitochondria as well as in the soluble phase but is absent from nuclei and microsomes about 90% of the total activity in rat liver is found in the cytosol. The mitochondrial enzyme appears not to be a contaminant from the cjrtosol.

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. 

Murant, R.S., Gibson, S.L., and Hilf, R., Photosensitizing effects of Photofrin II on the site-selected mitochondrial enzymes adenylate kinase and monoamine oxidase. Cancer Res., 47, 4323, 1987. 

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