HIGH ACTIVITIES OF GLUTAMINE TRANSAMINASE-K (DICHLOROVINYLCYSTEINE BETA-LYASE) AND OMEGA-AMIDASE IN THE CHOROID-PLEXUS OF RAT-BRAIN

Certain halogenated hydrocarbons, e.g., dichloroacetylene, are nephrot oxic to experimental animals and neurotoxic to humans; cysteine-S-conj ugate beta-lyases may play a role in the nephrotoxicity. We now show t hat with dichlorovinylcysteine as substrate the only detectable cystei ne-S-conjugate beta-lyase in rat brain homogenates is identical to glu tamine transaminase K. The predominant (mitochondrial) form of glutami ne transaminase K in rat brain was shown to be immunologically distinc t from the predominant (cytosolic) form of the enzyme in rat kidney. G lutamine transaminase K and omega-amidase (constituents of the glutami nase II pathway) activities were shown to be widespread throughout the rat brain. However, the highest specific activities of these enzymes were found in the choroid plexus. The high activity of glutamine trans aminase K in choroid plexus was also demonstrated by means of an immun ohistochemical staining procedure. Glutamine transaminase K has a broa d specificity toward amino acid and alpha-keto acid substrates. The om ega-amidase also has a broad specificity; presumably, however, the nat ural substrates are alpha-ketoglutaramate and alpha-ketosuccinamate, t he alpha-keto acid analogues of glutamine and asparagine, respectively . The high activities of both glutamine transaminase K and omega-amida se in the choroid plexus suggest that the two enzymes are linked metab olically and perhaps are coordinately expressed in that organ. The dat a suggest that the natural substrate of glutamine transaminase K in ra t brain is indeed glutamine and that the metabolism of glutamine throu gh the glutaminase 11 pathway (i.e., L-glutamine and alpha-keto acid - -> alpha-ketoglutarate and L-amino acid + ammonia) is an important fun ction of the choroid plexus. Moreover, the present findings also sugge st that any explanation of the neurotoxicity of halogenated xenobiotic s must take into account the role of glutamine transaminase K and its presence in the choroid plexus.