PHYSIOLOGY OF G6PD

PHYSIOLOGY OF G6PD

ot only is it important to learn about the molecular biology of G6PD, but also the physiology of G6PD is important as well. The function of the normal G6PD enzyme is critical to human survival.

The G6PD enzyme catalyzes an oxidation/reduction reaction. Oxidation/reduction reactions function in transferring electrons from one molecule to another; oxidation is the loss of electrons and reduction is the gain of electrons. As illustrated in figure 3, the G6PD enzyme functions in catalyzing the oxidation of glucose-6-phosphate to 6-phosphogluconate, while concomitantly reducing nicotinamide adenine dinucleotide phosphate (NADP+ to NADPH); or, in terms of electron transfer, glucose-6-phosphate loses two electrons to become 6-phosphogluconate and NADP+ gains two electrons to become NADPH. This is the first step in the pentose phosphate pathway. This pathway, or shunt, as it is sometimes called, produces the 5- carbon sugar, ribose, which is an essential component of both DNA and RNA. There are other metabolic pathways, however, that can produce ribose if there is a deficiency in G6PD (Yoshida & Beutler, 1986).

In addition to producing the 5-carbon sugar ribose, G6PD is also responsible for maintaining adequate levels of NADPH inside the cell. NADPH is a required cofactor in many biosynthetic reactions. NADPH is also used to keep glutathione, a tri-peptide, in its reduced form (see Figure 3 ). Reduced glutathione acts as a scavenger for dangerous oxidative metabolites in the cell; it converts harmful hydrogen peroxide to water with the help of the enzyme, glutathione peroxidase (Yoshida & Beutler, 1986). There are other metabolic pathways that can generate NADPH in all cells, except in red blood cells where other NADPH-producing enzymes are lacking (Scriver et al., 1995).This has a profound effect on the stability of red blood cells since they are especially sensitive to oxidative stresses in addition to having only one NADPH-producing enzyme to remove these harmful oxidants. This is why G6PD deficient individuals are not prescribed oxidative drugs, such as those listed in Table 2, because the red blood cells in these individuals are not able to handle this stress and consequently hemolysis ensues.