Genetics
Human glucokinase is coded for by the GCK gene on chromosome 7. This single autosomal gene has 10 exons. Genes for glucokinase in other animals are homologous to human GCK.
A distinctive feature of the gene is that it begins with two promoter regions. The first exon from the 5' end contains two tissue-specific promoter regions. Transcription can begin at either promoter (depending on the tissue) so that the same gene can produce a slightly different molecule in liver and in other tissues. The two isoforms of glucokinase differ only by 13-15 amino acids at the N-terminal end of the molecule, which produces only a minimal difference in structure. The two isoforms have the same kinetic and functional characteristics.
The first promoter from the 5' end, referred to as the "upstream" or neuroendocrine promoter, is active in pancreatic islet cells, neural tissue, and enterocytes (small intestine cells) to produce the "neuroendocrine isoform" of glucokinase. The second promoter, the "downstream" or liver promoter, is active in hepatocytes and directs production of the "liver isoform". The two promoters have little or no sequence homology and are separated by a 30 kbp sequence which, as of yet, has not been shown to incur any functional differences between isoforms. The two promoters are functionally exclusive and governed by distinct sets of regulatory factors, so that glucokinase expression can be regulated separately in different tissue types. The two promoters correspond to two broad categories of glucokinase function: In liver, glucokinase acts as the gateway for the "bulk processing" of available glucose, while, in the neuroendocrine cells, it acts as a sensor, triggering cell responses that affect body-wide carbohydrate metabolism.
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