MOLECULAR BIOLOGY OF G6PD
MOLECULAR BIOLOGY OF G6PD
t is just as important to learn about
the molecular biology of G6PD as it is to learn about the genetics of this
condition. The molecular data of the G6PD enzyme is summarized in
Table 1.
Table 1 shows that the G6PD gene consists of 13 exons, which are the regions of the DNA that code for the enzyme, and 12 introns, which are intervening sequences (Scriver et al., 1995). The intervening sequences are "junk" DNA which serve no purpose in the enzyme's function. The enzyme's function is determined, however, by the sequence and size of the G6PD gene and the mRNA encoded by the gene, which are 18,500 and 2,269 base pairs in length, respectively (Scriver et al., 1995). The entire genomic sequence of the G6PD gene can be found in the original research article by Chen and associates (1991). However, the complete 3-dimensional structure of the enzyme, which determines the active enzyme's functional properties, has not yet been determined.
G6PD, in its active enzyme form, is made up of either two or four identical subunits, each having a molecular mass of about 59 kilo-daltons; this is more than three times as large as the hemoglobin molecule, which is the principal oxygen carrying molecule in humans (Scriver et al., 1995).
This molecular data has led researchers to ask, "What is causing G6PD deficiency on the molecular level?" Most individuals with G6PD deficiency have a qualitative abnormality in the structure of the G6PD enzyme (Scriver et al., 1995). Several models have been proposed suggesting possible reasons for why an abnormal enzyme is not fully active. Sharff has suggested that the decreased stability of a mutated enzyme results either from a change in the conformation of the G6PD molecule or from an increase in its susceptibility to proteolytic enzymes (Sharff, 1991, cited in Scriver et al., 1995). In either case, the G6PD enzyme is not fully active when it is mutated.
Molecular renditions of parts of the DNA containing the G6PD Gene
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THE G6PD DEFICIENCY HOMEPAGE