Question 1

Which of the following represents the enzyme deficiency that leads to "essential fructosuria"?
A) fructose-1-phosphate aldolase (aldolase B)
B) fructose-1,6-bisphosphate aldolase (aldolase A)
C) fructokinase
D) hexokinase
E) 6-Phosphofructo-1 kinase, PFK1

Accepted Answer

Essential fructosuria is caused by a deficiency in fructokinase, which is responsible for the phosphorylation of fructose to fructose-1-phosphate in the liver.  Essential fructosuria is a benign metabolic disorder caused by the lack of fructokinase which is normally present in the liver, pancreatic islets, and kidney cortex. The fructosuria of this disease depends on the time and amount of fructose and sucrose intake. Since the disorder is asymptomatic and harmless, it may go undiagnosed.

Question 2

A child born and raised in Chicago planned to spend the summer on a relative's fruit farm and help with the harvest. The summer passed uneventfully, but several days after the harvest began, the child became jaundiced and very sick. On admission to the hospital the following clinical findings were recorded: in addition to the expected hyperbilirubinemia, the patient was hypoglycemic, had a markedly elevated rise in blood fructose concentration, and was hyperlactic acidemic. Further history taking revealed that during the harvest it was customary for the family to indulge in fruit-filled meals and to snack freely on fruit while carrying out the harvest. The elevated blood fructose in this child was most likely due to which of the following?
A) an allergic reaction to constituents in the fruit diet
B) defective hepatic aldolase B
C) defective hepatic fructokinase
D) defective hepatic fructose-1,6-bisphosphatase
E) defective hepatic glucokinase

Accepted Answer

The symptoms and elevated blood fructose suggest hereditary fructose intolerance, which is caused by a deficiency in aldolase B, leading to an accumulation of fructose-1-phosphate and subsequent metabolic disturbances.  Hereditary fructose intolerance is a potentially lethal disorder resulting from a lack of aldolase B which is normally present in the liver, small intestine, and kidney cortex. The disorder is characterized by severe hypoglycemia and vomiting following fructose intake. Prolonged intake of fructose by infants with this defect leads to vomiting, poor feeding, jaundice, hepatomegaly, hemorrhage, and, eventually, hepatic failure and death. The hypoglycemia that results following fructose uptake is caused by fructose- 1-phosphate inhibition of glycogenolysis, by interfering with the phosphorylase reaction, and inhibition of gluconeogenesis at the deficient aldolase step. Patients remain symptom free on a diet devoid of fructose and sucrose.

Question 3

Which of the following represents the enzyme deficiency that leads to "essential fructosuria"?
A) fructose-1-phosphate aldolase (aldolase B)
B) fructose-1,6-bisphosphate aldolase (aldolase A)
C) fructokinase
D) hexokinase
E) 6-Phosphofructo-1 kinase, PFK1

Accepted Answer

Essential fructosuria is caused by a deficiency in the enzyme fructokinase, which is responsible for the phosphorylation of fructose to fructose-1-phosphate in the liver. Essential fructosuria is a benign metabolic disorder caused by the lack of fructokinase which is normally present in the liver, pancreatic islets, and kidney cortex. The fructosuria of this disease depends on the time and amount of fructose and sucrose intake. Since the disorder is asymptomatic and harmless, it may go undiagnosed

Question 4

A child born and raised in Chicago planned to spend the summer on a relative's fruit farm and help with the harvest. The summer passed uneventfully, but several days after the harvest began, the child became jaundiced and very sick. On admission to the hospital the following clinical findings were recorded: in addition to the expected hyperbilirubinemia, the patient was hypoglycemic, had a markedly elevated rise in blood fructose concentration, and was hyperlactic acidemic. Further history taking revealed that during the harvest it was customary for the family to indulge in fruit-filled meals and to snack freely on fruit while carrying out the harvest. The elevated blood fructose in this child was most likely due to which of the following?
A) an allergic reaction to constituents in the fruit diet
B) defective hepatic aldolase B
C) defective hepatic fructokinase
D) defective hepatic fructose-1,6-bisphosphatase
E) defective hepatic glucokinase

Accepted Answer

The symptoms and elevated blood fructose suggest hereditary fructose intolerance, which is caused by a deficiency in hepatic aldolase B.  Hereditary fructose intolerance is a potentially lethal disorder resulting from a lack of aldolase B which is normally present in the liver, small intestine, and kidney cortex. The disorder is characterized by severe hypoglycemia and vomiting following fructose intake. Prolonged intake of fructose by infants with this defect leads to vomiting, poor feeding, jaundice, hepatomegaly, hemorrhage, and, eventually, hepatic failure and death. The hypoglycemia that results following fructose uptake is caused by fructose- 1-phosphate inhibition of glycogenolysis, by interfering with the phosphorylase reaction, and inhibition of gluconeogenesis at the deficient aldolase step. Patients remain symptom free on a diet devoid of fructose and sucrose.

Question 5

A 1-year-old girl is being examined by her physician because of a 3-month history of intermittent vomiting, shakiness, and a failure to thrive. The symptoms began when breast-feeding stopped and fruit and vegetables were added to her diet. Her current size is below the fifth percentile for length and weight. Upon physical examination the physician notes jaundice and hepatomegaly. Intravenous administration of fructose results in hypoglycemia and hypophosphatemia. Deficiency of which of the following hepatic enzymes is the most likely cause of the disorder in this patient?
A) aldolase B
B) fructokinase
C) galactose-1-phosphate uridyltransferase
D) glucose 6-phosphatase
E) glycogen phosphorylase

Accepted Answer

The symptoms and history are consistent with hereditary fructose intolerance, which is caused by a deficiency of aldolase B. This condition leads to the accumulation of fructose-1-phosphate, causing hypoglycemia and hypophosphatemia when fructose is ingested. Hereditary fructose intolerance is a potentially lethal disorder resulting from a lack of aldolase B which is normally present in the liver, small intestine, and kidney cortex. The disorder is characterized by severe hypoglycemia and vomiting following fructose intake. Prolonged intake of fructose by infants with this defect leads to vomiting, poor feeding, jaundice, hepatomegaly, hemorrhage, and, eventually, hepatic failure and death. The hypoglycemia that results following fructose uptake is caused by fructose- 1-phosphate inhibition of glycogenolysis, by interfering with the phosphorylase reaction, and inhibition of gluconeogenesis at the deficient aldolase step. Patients remain symptom free on a diet devoid of fructose and sucrose.

Question 6

Individuals harboring a mutation in the aldolase B gene are subject to severe hypoglycemia upon consumption of fructose. The hypoglycemia can be explained by an impairment in glycogen phosphorylase-mediated glucose release from glycogen in response to glucagon. This metabolic defect can best be explained by which of the following?
A) allosteric activation of glycogen synthase by fructose 1-phosphate
B) allosteric inhibition of phosphorylase by fructose 1-phosphate
C) depletion of the phosphate pool required by phosphorylase
D) the depletion in ATP leads to activation of AMPK which phosphorylates and inhibits phosphorylase
E) trapping of ATP in the form of fructose 1-phosphate

Accepted Answer

The accumulation of fructose 1-phosphate due to aldolase B deficiency depletes inorganic phosphate, which is necessary for glycogen phosphorylase activity, impairing glycogen breakdown and leading to hypoglycemia.  Glycogen phosphorylase carries out a phosphorolysis reaction on glycogen utilizing inorganic phosphate in the process of this reaction. Hypoglycemia after fructose ingestion is caused by accumulation of fructose 1-phosphate which simultaneously depletes inorganic phosphate pools, thereby inhibiting glycogenolysis at the level of glycogen phosphorylase which requires inorganic phosphate for activity.

Question 7

Patients with aldolase B gene mutations are required to avoid certain foods and products that contain fructose as their consumption can lead to significant hypoglycemia. In addition to fructose, consumption of which of the following carbohydrates must be avoided in these patients?
A) cellulose
B) glucose
C) lactose
D) maltose
E) sorbitol

Accepted Answer

Patients with aldolase B gene mutations have hereditary fructose intolerance. Sorbitol is a sugar alcohol that can be converted to fructose in the body, so it must be avoided.  Sorbitol is a sugar often used in the pharmaceutical and food industries as a thickener or for the production of transparent gels such as in certain toothpastes. Sorbitol can be metabolized to fructose via the action of sorbitol dehydrogenase. Therefore, it is important that patients with hereditary fructose intolerance monitor food and pharmaceuticals for the presence of sorbitol as ingestion can lead to significant health complications.

Question 8

Within the hypothalamus, metabolism of fructose results in a significant drop in the ATP:ADP ratio. The resulting increase in AMP results in altered metabolic pathways that in turn result in an increased desire for food intake. Which of the following metabolic changes is a contributing factor to the increased feeding behaviors associated with fructose consumption?
A) decreased fatty acid synthesis
B) decreased glycolysis
C) decreased fatty acid oxidation
D) increased fatty acid oxidation
E) increased gluconeogenesis

Accepted Answer

Metabolism of fructose in the brain exerts an orexigenic (feeding desire) effect. Hypothalamic fructose metabolism rapidly depletes ATP levels in the hypothalamus resulting in increased AMP levels. The rise in AMP results in activation of AMPK which, in turn, leads to phosphorylation and inhibition of acetyl-CoA carboxylase (ACC [rate-limiting enzyme of fatty acid synthesis]) with the result being decreased malonyl-CoA levels in the hypothalamus. Decreased malonyl-CoA levels result in reduced inhibition of fatty acid uptake into the mitochondrial. Thus, when malonyl-CoA levels fall fat oxidation increases. This reduces the overall level of fatty acids and fatty acid esters within cells of the hypothalamus, triggering the synthesis and release of orexigenic peptides with an increased desire for food intake.

Question 9

Hypothalamic fructose metabolism is associated with an increased desire for food intake. Altered feeding behaviors with fructose consumption are related to changing levels of which of the following metabolic intermediates?
A) acetyl-CoA
B) citrate
C) fructose 2,6-bisphosphate
D) malonyl-CoA
E) pyruvate

Accepted Answer

Malonyl-CoA is a key metabolic intermediate that regulates feeding behavior. It is involved in the signaling pathway that affects appetite control in the hypothalamus. Changes in its levels can influence the desire for food intake.  Hypothalamic fructose metabolism bypasses rapidly depletes ATP levels resulting in increased AMP levels. The rise in AMP results in activation of AMPK which, in turn, leads to phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) with the result being decreased malonyl-CoA levels in the hypothalamus. Hypothalamic malonyl-CoA is a key intermediate in the regulation of feeding behavior and overall energy balance initiated via signaling cascades within the hypothalamus. During periods when energy expenditure exceeds intake, such as during fasting, malonyl-CoA levels in the hypothalamus are low. Following food intake there is a rapid rise in hypothalamic malonyl-CoA levels. The changes in hypothalamic malonyl-CoA levels are followed quickly by changes in expression of orexigenic and anorexigenic peptides.

Question 10

Although fructose-1,6-bisphosphatase (F1,6BPase) deficiency can lead to infant mortality due to severely impaired gluconeogenesis, beyond childhood afflicted individuals develop hypoglycemia usually only associated with fasting or febrile infections. Given the role of F1,6BPase in overall carbohydrate metabolism, which of the following metabolites would be expected to increase in the plasma of these patients following depletion of hepatic glycogen stores?
A) acetyl-CoA
B) cholesterol
C) free fatty acids
D) lactate
E) pyruvate

Accepted Answer

In F1,6BPase deficiency, gluconeogenesis is impaired, leading to an accumulation of glycolytic intermediates like lactate, especially during fasting when glycogen stores are depleted. During normal hepatic gluconeogenesis, the major substrates for glucose synthesis are alanine, pyruvate, and lactate. Defective F1,6BPase would restrict the flow of alanine and lactate conversion to pyruvate and the subsequent input of pyruvate into gluconeogenesis. The net effect would be a significant increase in circulating levels of lactate.

Question 11

An advertisement promotes energy bars containing fructose as ideal food to take on extreme mountain-climbing expeditions. Which of the following statements concerning fructose absorption is true?
A) absorption of fructose into an intestinal epithelial cell is by facilitated transport and thus does not require energy
B) metabolism of fructose generates more energy than glucose
C) some fructose is already absorbed in the mouth and hence is the fastest way to get energy
D) the presence of fructose aids in absorption of vitamin A, C, and D
E) the presence of fructose inhibits reabsorption of glucose, which is then more readily available for muscle activity

Accepted Answer

Fructose is absorbed into intestinal epithelial cells by facilitated transport via the GLUT5 transporter, which does not require energy. Carbohydrate absorption occurs at enterocytes of the upper region of small intestinal villi. Fructose absorption is via the facilitated transporters GLUT5 across the apical enterocyte membrane and GLUT2 across the basolateral enterocyte. Glucose and galactose on the other hand are transported into enterocytes on carriers in combination with a sodium ion. The energy for this secondary active transport is provided by the electrochemical sodium gradient that is created by Na/K-ATPases. Experimental conditions that collapse the sodium electrochemical gradient, hypoxia, or poisoning of the Na/K-ATPase by ouabain inhibit glucose, but not fructose absorption. Nevertheless, the physiological importance of "saving energy" under extreme conditions such as mountain climbing through the use of fructose as energy source is questionable.

Quiz 11: Carbohydrates: Fructose Metabolism and Feeding Behaviors

Which of the following represents the enzyme deficiency that leads to "essential fructosuria"?

Which of the following represents the enzyme deficiency that leads to "essential fructosuria"?

Patients with aldolase B gene mutations are required to avoid certain foods and products that contain fructose as their consumption can lead to significant hypoglycemia. In addition to fructose, consumption of which of the following carbohydrates must be avoided in these patients?

Hypothalamic fructose metabolism is associated with an increased desire for food intake. Altered feeding behaviors with fructose consumption are related to changing levels of which of the following metabolic intermediates?

An advertisement promotes energy bars containing fructose as ideal food to take on extreme mountain-climbing expeditions. Which of the following statements concerning fructose absorption is true?