Novel human glutamate dehydrogenase expressed in neural and testicular tissues and encoded by an X-linked intronless gene

Glutamate dehydrogenase, an enzyme central to glutamate metabolism, is deficient in patients with heterogeneous neurological disorders characterized by multiple system atrophy. There is evidence for multiplicity of human glutamate dehydrogenase, which may account for the heterogeneity of the above disorders. However, only one mRNA that is encoded by an intron-containing gene (GLUD1) is presently known. Because blindness due to neuroretinal degeneration can occur in rare forms of multiple system atrophy, we searched for retina-specific GLUD mRNA(s) by screening a λgt10 library derived from human retina. A novel cDNA encoded by an X chromosome-linked intronless gene, designated GLUD2, was isolated and characterized. Reverse transcription- polymerase chain reaction analysis of human tissues revealed that the novel cDNA is expressed in human retina, testis, and, at lower levels, brain. In vitro translation of mRNAs derived from GLUD1 and GLUD2 genes generated proteins with distinct electrophoretic characteristics. The retinal cDNA was expressed in the baculovirus heterologous system, producing a protein capable of catalyzing the oxidative deamination of glutamate. The mobility of the expressed protein on SDS-polyacrylamide gel electrophoresis and its catalytic properties were very similar to those of the naturally occurring human brain glutamate dehydrogenases. The novel gene will be useful for understanding the biology of human neural and testicular tissues and in the study of X-linked neurodegenerative disorders.