Aspartate aminotransferase interaction

Yudkoff, M., Nelson, D., Daikhin, Y. etal. Tricarboxylic acid cycle in rat brain synaptosomes. Fluxes and interactions with aspartate aminotransferase and malate/aspar-tate shuttle. /. Biol. Chem. 269 27414-27420,1994. 

Drug/Lab test interactions Tinidazole may interfere with certain serum chemistry values, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. 

Many enzymes exist within a cell as two or more isoenzymes, enzymes that catalyze the same chemical reaction and have similar substrate specificities. They are not isomers but are distinctly different proteins which are usually encoded by different genes.22 23 An example is provided by aspartate aminotransferase (Fig. 2-6) which occurs in eukaryotes as a pair of cytosolic and mitochondrial isoenzymes with different amino acid sequences and different isoelectric points. Although these isoenzymes share less than 50% sequence identity, their internal structures are nearly identical.24-27 The two isoenzymes, which also share structural homology with that of E. coli,28 may have evolved separately in the cytosol and mitochondria, respectively, from an ancient common precursor. Tire differences between them are concentrated on the external surface and may be important to as yet unknown interactions with other protein molecules. 

Fig. 1.2 Comparison of sequences of aspartate aminotransferases from different species. The residues are numbered according to the sequence of pig cAspAT.13 Possible deletions introduced into the sequences are indicated by hyphens. Residues that are invariant in pig c- and m-AspAT s are boxed, those that are invariant in pig AspAT s and coli AspAT are indicated as bold letters, and those that are directly interacting with substrate or coenzyme are marked as. ...

Schilling, K. and Waldmann-Meyer, H., The interaction of bromophenol blue with serum albumin and gamma-globuhn in acid medium. Arch. Biochem. Biophys. 64, 291-301, 1956 Cohen, A.H., Temperature jump studies of the binding of bromophenol blue to beta-lactoglobulin in the vicinity of the N-R transition, J. Biol. Chem. 245,738-745,1970 Harruff, R.C. and Jenkins, W.T., The binding of bromophenol blue to aspartate aminotransferase. Arch. Biochem. Biophys. 

Aspartate aminotransferase is the prototype of a large family of PLP-dependent enzymes. Comparisons of amino acid sequences as well as several three-dimensional structures reveal that almost all transaminases having roles in amino acid biosynthesis are related to aspartate aminotransferase by divergent evolution. An examination of the aligned amino acid sequences reveals that two residues are completely conserved. These residues are the lysine residue that forms the Schiff base with the pyridoxal phosphate cofactor (lysine 258 in aspartate aminotransferase) and an arginine residue that interacts with the a-carboxylate group of the ketoacid (see Figure 23.11). 

Yet another component of the toxicity was found to be the elevation of seram transantinases (e.g., aspartate aminotransferase, or AST), which is consistent with the accumulation of significant amounts of systemically administered complex in the liver (see above). These toxicities are not simply a consequence of the presence of plasmid DNA in the blood, which is rapidly degraded and much less toxic. Rather it is a consequence of the stabilization of the pDNA in the serum by cationic lipid and the subsequent interaction of tins complexed DNA with host blood components and cells (72,73). 

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