Identification of two human glutaminase loci and tissue-specific expression of the two related genes

Glutaminolysis is initiated by either of two isoforms, K- and L-types, of t he enzyme phosphate-activated glutaminase. The chromosomal localization, ge nomic organization: and the tissue-specific expression of the genes have be en investigated in the human by using isoform-specific cDNA probes. Results obtained from radiation hybrid mapping experiments assigned the K-glutamin ase gene to human Chromosome (Chr) 2, and a second locus for L-glutaminase in Chr 12 was identified. Southern blot analysis with the L-cDNA probe show ed hybridization to a single restriction fragment, while four to seven frag ments were found to hybridize to the K-cDNA probe. The distribution of huma n glutaminase expression was also investigated: the L-cDNA probe detected a single band of 2.4 kb in liver, brain, and pancreas, whereas a single tran script of approximately 4.4 kb was detected in kidney, brain, heart, placen ta, lung, and pancreas by using the K-cDNA probe. This work provides eviden ce that the human liver and kidney glutaminase isozymes are encoded by sepa rate genes located on different chromosomes; furthermore, the expression pa ttern in human tissues revealed for both isoenzymes differs notably from th e paradigm based upon the isoenzyme distribution in rats.