An ancient molecule with novel function: Alanine aminotransferase as a lipopolysaccharide binding protein with bacteriocidal activity.

Xiaoli Jing, Shicui Zhang

Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China.

Developmental and comparative immunology 2011 Jan

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Alanine aminotransaminase (ALT) has been identified from bacteria to plants to animals including humans. The increase in serum ALT is regarded as an index for clinical diagnosis of liver function in humans. However, ALT elevation is also reported in non-liver injury conditions and in apparently healthy people, suggesting it may play a fundamental role physiologically. Herein we isolated an alt homolog, Amphialt, from Branchiostoma japonicus, an intermediatary species from invertebrates to vertebrates, which encoded a polypeptide of 500 amino acids with more than 62 and 52% sequence identity to vertebrate and invertebrate ALT isoenzymes, respectively. It was constitutively expressed in many tissues including the hepatic caecum, the precursor of liver, and its expression in the caecum was significantly up-regulated by challenge with lipopolysaccharides (LPS). Strikingly, recombinant AmphiALT, with a specific activity of 0.114±0.02U/mg, was capable of specifically binding to the Gram-negative bacteria Escherichia coli and Aeromonas hydrophila and to their conserved molecule LPS, as well as inhibiting the growth of E. coli and causing its lysis. In contrast, AmphiALT did not bind to the Gram-positive bacteria Staphyloccocus aureus and Bacillus subtilis as well as their conserved molecule LTA. In addition, a high homology noted between amphioxus and mammalian ALT sequences suggested a functional conservation of ALT evolutionarily, hinting at the clue that mammalian ALT may also play an antibacterial role similar to that of AmphiALT. Taken together, it is proposed that AmphiALT is an immune-relevant molecule capable of identifying LPS and causing damage to Gram-negative bacteria like E. coli and A. hydrophila. It also bolsters the notion that the hepatic caecum of amphioxus is the precursor of vertebrate liver, acting as a major tissue in acute phase response. Copyright © 2010 Elsevier Ltd. All rights reserved.

Citation

Xiaoli Jing, Shicui Zhang. An ancient molecule with novel function: Alanine aminotransferase as a lipopolysaccharide binding protein with bacteriocidal activity. Developmental and comparative immunology. 2011 Jan;35(1):94-104