Human hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase) encoded at 1p36: coding sequence and expression

Area of Science:

• Biochemistry
• Genetics
• Molecular Biology

Background:

• Glucose-6-phosphate dehydrogenase (G6PD) is a crucial enzyme in cellular metabolism.
• Understanding the genetic basis of G6PD and its human equivalent is important for metabolic research.

Purpose of the Study:

• To isolate and sequence the cDNA clone for human G6PD (hexose-6-phosphate dehydrogenase, H6PD).
• To analyze the genomic structure and chromosomal localization of the human H6PD gene.
• To investigate the evolutionary relationship between human H6PD and other G6PD enzymes.

Main Methods:

• cDNA cloning and sequencing using a rabbit microsomal G6PD sequence as a reference.
• Bioinformatic analysis of genomic databases for gene localization and structure.
• Sequence homology analysis to compare human H6PD with other G6PD proteins.

Main Results:

• Isolated and sequenced a human cDNA clone for G6PD/H6PD.
• Localized the H6PD gene to chromosome 1p36.
• The gene spans 37 kb with 5 exons; the fifth exon encodes over half the protein.
• Identified an unusually long 3' untranslated sequence in the mRNA.
• Observed significant homology with X-linked G6PD, suggesting a common ancestor.
• Found limited homology in the C-terminal region with proteins of unknown function and Plasmodium falciparum G6PD.

Conclusions:

• The human H6PD gene has a distinct genomic structure compared to X-linked G6PD.
• The evolutionary divergence of H6PD and G6PD occurred early in evolution.
• The C-terminal domain of H6PD may have functions beyond glucose metabolism and shares evolutionary links with microbial proteins.