Glucose-6-phosphate dehydrogenase removal

Oxidized, denatured hemoglobin forms aggregates, which can become attached to the inner surface of the red cell, known as Heinz bodies. This leads to damage to the red cell, which may result in direct destruction of the cell, which can be shown in vitro, or removal from the circulation by the spleen in vivo. When caused by Fava beans, the syndrome is known as Favism. As the deficient enzyme (glucose-6-phosphate dehydrogenase) is intrinsic to the red cell, exposure of such cells in vitro to suitable drugs will lead to cell damage and death. 

Exley et al. [61] found aluminum in practically all reagents used in a study of the inhibition of hexokinase activity by this element. The way to overcome the problem was cleaning the solutions using an aminophosphonate chelation resin. The procedure reduced the contamination of ATP and NADP to approximately 5% and 10% of their initial values, respectively, but the resin was ineffective in removing aluminum from magnesium acetate or the enzyme glucose 6-phosphate dehydrogenase. Probably the conditions were not favorable for the resin to pick up the aluminum ions from these solutions. It is important to remember that, if there is an affinity between aluminum and the species in solution, a competition between this species and the resin will take place. 

Chelation therapy is usually the treatment of choice. Both CaNai-EDTA (calcium disodium salt of ethylenediaminetetraacetic acid) and British Antilewisite compound (BAL 2,3-dimercaptopropanol) are commonly used to remove lead from the body. Both are administered via intramuscular injection. BAL binds lead to sulfhydral groups and chelates metal from both inside and outside the cellular space. Lead removal through the bile and urine is increased within 30 min of administration. BAL is the common choice when there is known toxicity to the kidney, but it is contraindicated if there is liver failure or glucose-6-phosphate dehydrogenase deficiency. BAL treatment has produced a number of adverse reactions, including nausea, vomiting, tachycardia, and fever. 

As discussed above, an enzymatic reaction is usually found to be more rapid in one direction than the other so that the reaction is virtually irreversible.If the product of the reaction in one direction is removed as it is formed (Le., because it is the substrate of a second enzyme present in the reaction mixture), the equilibrium of the first enzymatic process is displaced so that the reaction may continue to completion in that direction. Reaction sequences in which the product of one enzyme-catalyzed reaction becomes the substrate of another enzyme, often through many stages, are characteristic of metabolic processes. Analytically, several enzymatic reactions also may be Unked together to provide a means of measuring the activity of the first enzyme or the concentration of the initial substrate in the chain. For example, the activity of creatine kinase is usually measured by a series of linked reactions, and glucose can be determined by consecutive reactions catalyzed by hexokinase and glucose-6-phosphate dehydrogenase. 

Figure 6.63 Substrate activation mechanisms and stereochemistry (shown in the sense of ketone reduction) for (a) aldose reductases, (b) long-chain dehydrogenases, (c) glucose-6-phosphate dehydrogenase and (d) sorbitol dehydrogenase. The glutamate ligand to Zn is shown removed in the complex with fructose, but this is speculative.

An otherwise healthy 32-year-old woman received prilocaine 60 mg for removal of a gluteal abscess and developed symptoms of suspected methemoglobinemia, with dizziness, fever, and headache 1 hour after surgery and peripheral cyanosis and tachycardia 3 hours later [75 ]. She was given 5 ml of methylthioninium chloride 1% and her symptoms resolved within 30 minutes. Erythrocyte glucose-6-phosphate-dehydrogenase activity was normal. 

The pentose phosphate pathway can be sectioned into two phases the oxidative phase and the non-oxidative phase. During the oxidative phase (Figure 11.13), glucose 6-phosphate is oxidized by the removal of electrons which are accepted by the coenzyme, NADP, and decarboxylated to yield ribose 5-phosphate. The first reaction involves oxidation by the NADP" -specific enzyme glucose-6-phosphate dehydrogenase with concomitant reduction of NADP to produce 6-phosphoglucono-1,5-lactone. The lactone, although unstable and liable... 

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