Question 1

Which of the following is a congenital defect in which enzyme may cause hemolytic anemia following administration of the antimalarial drug primaquine?

Accepted Answer

Glucose-6-phosphate dehydrogenase deficiency is a congenital defect that can lead to hemolytic anemia when exposed to certain drugs like primaquine, due to the inability to protect red blood cells from oxidative damage.  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.

Question 2

The transketolase enzyme of the pentose phosphate pathway requires which of the the following for maximal activity?

Accepted Answer

Transketolase requires thiamine pyrophosphate (TPP) as a cofactor for its activity in the pentose phosphate pathway.  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.

Question 3

In which of the following tissues would pentose phosphate pathway be expected to be the least active?

Accepted Answer

The pentose phosphate pathway is least active in skeletal muscle because this tissue primarily relies on glycolysis and oxidative phosphorylation for energy, and it does not have a high demand for NADPH or ribose-5-phosphate, which are the main products of the pentose phosphate pathway.  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

Question 4

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?

Accepted Answer

The defect in chronic granulomatous disease is typically in the NADPH oxidase enzyme complex, which is responsible for generating reactive oxygen species. G6PDH (glucose-6-phosphate dehydrogenase) is involved in the pentose phosphate pathway, which provides NADPH necessary for the NADPH oxidase function. However, the direct enzyme defect in CGD is in the NADPH oxidase itself, not G6PDH.

Question 5

A 22-year-old black male was given the antimalaria drug primaquine to take while on an expedition on the Amazon River. After taking the drug, he developed an acute anemia. The anemia was secondary to an intravascular hemolytic crisis. This crisis was reversed when he discontinued taking the primaquine. This drug-induced hemolytic anemia arises in persons who have a deficienc in which of the following enzymes?

Accepted Answer

The hemolytic anemia is due to a deficiency in glucose-6-phosphate dehydrogenase (G6PD), which is crucial for protecting red blood cells from oxidative damage. Primaquine can induce oxidative stress, leading to hemolysis in individuals with G6PD deficiency. 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 G6PDH deficiency and, thus, this drug should not be administered to anyone with a deficiency of this enzyme

Question 6

Oxidative breakdown of glucose can occur in certain mammalian cells by mechanisms other than classic glycolysis. In most of these cells, G6P is oxidized to 6-phosphogluconate. Which of the following represents the next intermediate in this alternative glucose oxidation pathway?

Accepted Answer

The oxidative breakdown of glucose via the pentose phosphate pathway involves the decarboxylation of 6-phosphogluconate to produce ribulose-5-phosphate, an aldopentose.  The next reaction in the PPP, catalyzed by 6-phosphogluconate dehydrogenase, oxidatively decarboxylates 6-phosphogluconate to the 5-carbon aldose sugar, ribulose 5-phopshate.

Question 7

A 2-year-old child who is a native of East Africa has been diagnosed with a deficiency in G6PDH. Following consumption of fava beans the child experiences a mild hemolytic anemia. Which of the following symptoms would also likely be present in this child?

Accepted Answer

Favism is the term associated with the hemolytic anemia that results from the consumption of fava beans in individuals with deficiencies in G6PDH. The deficiency prevents erythrocytes from coping with the oxidative stress induced by metabolism of substances in fava beans. The continued hemolysis leads to hyperbilirubinemia, splenomegaly, and skeletal abnormalities in infants. The facial anomalies associated with favism are due to repeated episodes of intracranial hemorrhage.

Question 8

Which of the following represents the main function of the pentose phosphate pathway?

Accepted Answer

The pentose phosphate pathway primarily generates NADPH and ribose-5-phosphate (a pentose sugar), which are essential for biosynthetic reactions and nucleotide synthesis, respectively.  The 2 major functions of the PPP are (1) the generation of reducing equivalents, in the form of NADPH, for reductive biosynthesis reactions within cells and (2) to provide the cell with ribose 5-phosphate (R5P) for the synthesis of the nucleotides and nucleic acids.

Question 9

The reactions of the PPP using glucose 6-phosphate as the initial substrate are best described by which of the following statements?

Accepted Answer

The pentose phosphate pathway (PPP) produces 2 moles of NADPH for each mole of CO2 released when glucose 6-phosphate is metabolized to ribulose 5-phosphate.

Question 10

A 50-year-old alcoholic male presents with pain, numbness, tingling, and weakness in his feet. He is diagnosed with thiamine deficiency. Thiamine is required as a cofactor for which of the following enzymes?

Accepted Answer

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.

Question 11

Which of the following enzymes represents a key regulated enzyme of the PPP?

Accepted Answer

G6PDH (Glucose-6-phosphate dehydrogenase) is the key regulated enzyme of the Pentose Phosphate Pathway (PPP), as it catalyzes the first step and is the rate-limiting enzyme of the pathway.  The key regulated enzyme of the PPP, G6PDH, catalyzes the initial oxidation reaction of the pathway

Question 12

Xylulose 5-phosphate can be formed from ribulose 5-phosphate via the action of which of the following enzymes?

Accepted Answer

Phosphopentose epimerase catalyzes the conversion of ribulose 5-phosphate to xylulose 5-phosphate by epimerizing the hydroxyl group at the third carbon.  The conversion of ribulose 5-phosphate to xylulose 5-phosphate is an epimerization reaction. This reaction is catalyzed by the phosphopentose epimerase more commonly called ribulose 5-phosphate epimerase.

Question 13

The PPP is active in liver, adipose tissue, adrenal cortex, thyroid, erythrocytes, testis, and lactating mammary gland. Why is the pathway less active in skeletal muscle?

Accepted Answer

Muscle tissue contains very small amounts of the dehydrogenases of the PPP, which limits the activity of the pathway in skeletal muscle.  The enzymes of the PPP are expressed at highest levels in tissues that carry out high rates of lipid biosynthesis. Skeletal muscle, although active at de novo fatty acid synthesis, does not require high rates of fatty acid synthesis because it can acquire them readily from the blood. Therefore, expression of the oxidative enzymes of the PPP is at low levels in this tissue.

Question 14

While training for a triathlon, a 25-year-old female follows a high-carbohydrate diet that provides for adequate glycogen and fat synthesis. When she begins the competition, fatty acid synthesis stops. The best explanation for this is a decrease in which of the following?

Accepted Answer

During intense exercise, the demand for ATP increases, leading to a shift in metabolic pathways. The pentose phosphate pathway (PPP) is less active during exercise because the focus is on generating ATP through glycolysis and oxidative phosphorylation, rather than producing NADPH for fatty acid synthesis.  Fatty acid synthesis requires NADPH derived from the PPP via the oxidation of G6P. During strenuous exercise the vast majority of the glucose is shunted into glycolysis for complete oxidation. Therefore, little G6P is available for the PPP.

Question 15

A 32-year-old man of Mediterranean descent is brought to the physician because of a 2-day history of fatigue and shortness of breath. He recently had a urinary tract infection treated with trimethoprimsulfamethoxazole. His pulse is 100/minute. Physical examination shows pallor and scleral icterus. Laboratory studies show a decreased erythrocyte count and an increased serum bilirubin concentration that is mainly indirect. This patient's anemia is most likely due to failure of which of the following?

Accepted Answer

The patient likely has G6PD deficiency, common in individuals of Mediterranean descent, leading to hemolytic anemia due to oxidative stress from drugs like trimethoprim-sulfamethoxazole. This condition impairs erythrocyte protection against membrane oxidation.  Erythrocytes require a continuous source for NADPH to ensure that oxidized glutathione can be reduced by the glutathione peroxidase system. Glutathione is oxidized when it scavenges reactive oxygen species and by reducing oxidized membrane lipids. Administration of oxidizing drugs such as those of the sulfa class can lead to weakening of erythrocyte plasma membranes due to rapid depletion of reduced glutathione levels and inadequate NADPH-dependent reduction of the oxidized form.

Quiz 15: Carbohydrates: Pentose Phosphate Pathway