Chapter 15: Carbohydrates: Pentose Phosphate Pathway
Which of the following is a congenital defect in which enzyme may cause hemolytic anemia following administration of the antimalarial drug primaquine?
C. glucose-6-phosphate dehydrogenase
E. glyceraldehyde-3-phosphate dehydrogenase
Answer C: Primaquine is used to treat malaria since it causes lysis of erythrocytes that have been weakened by the presence of the parasite. When administered to humans, primaquine is metabolized into an arylhydroxylamine metabolite that exerts the hemotoxi effects. Primaquine causes methemoglobinemia in all patients. However, dangerous levels of methemoglobinemia only occur in patients with glucose-6-phosphate dehydrogenase (G6PDH) deficiency and, thus, this drug should not be administered to anyone with a deficiency in this enzyme.
The transketolase enzyme of the pentose phosphate pathway requires which of the the following for maximal activity?
Answer E: Transketolase functions to transfer 2-carbon groups from substrates of the PPP, thus rearranging the carbon atoms that enter this pathway. Like other enzymes that transfer 2-carbon groups, transketolase requires TPP as a cofactor in the transfer reaction.
In which of the following tissues would pentose phosphate pathway be expected to be the least active?
D. lactating mammary tissue
Answer E: The reactions of fatty acid biosynthesis and steroid biosynthesis utilize large amounts of NADPH. As a consequence, cells of the liver, adipose tissue, adrenal cortex, testis, and lactating mammary gland have high levels of the PPP enzymes. Skeletal muscle, although active at de novo fatty acid synthesis, have the lowest levels of expression of enzymes of the PPP.
Your patient is suffering from chronic granulomatous disease (CGD) which results in recurrent bouts of infection. CGD is characterized by an inability of phagocytic cells to kill invading microbes that they have engulfed because these cells lack the ability to generate reactive oxygen species such as H2O2. A defect in which of the following enzymes is most likely the cause of the phagocytic cell dysfunction?