Deck 10: Carbohydrates: Glycolysis and Glucose Homeostasis

Question 1

You have a patient exhibiting severe episodes of hypoglycemia. Measurement of circulating insulin and glucagon levels indicate that they are normal and responsive to cycles of feeding and fasting. Which of the following enzyme defects would most likely explain the hypoglycemia?

A) a constitutively active glycogen synthase
B) glycogen synthase that lacks the phosphorylase kinase target site
C) hepatic glucokinase with a K_m equal to that of muscle hexokinase
D) pancreatic glucokinase with a K_m equal to that of hepatic glucokinase
E) PFK1 that is nonresponsive to the allosteric effects of fructose-2,6-bisphosphate

Answer 1

C
EXPLANATION: The hepatic form of the glucosephosphorylating enzyme is referred to as glucokinase, which is a hexokinase isoform. Humans express 4 distinct hexokinases that exhibit different patterns of expression and kinetic activities relative to substrates and catalytic rates. Hepatic glucokinase has a K_m significantly higher than that of the hexokinase that is expressed in skeletal muscle. This prevents the liver from trapping glucose, thereby ensuring that peripheral tissues such as the brain and muscle have easy access to dietary carbohydrate. In the case of this patient, the expression of a variant glucokinase with a K_m similar to that of muscle hexokinase would result in significant trapping of glucose inside hepatocytes. The outcome would be expected to be periods of hypoglycemia as described.

Question 2

You are examining the effects of an experimental compound on the metabolic activities of primary hepatocytes in culture. You discover that addition of your compound to these cells activates changes in metabolic fluxes highly similar to those induced by addition of glucagon. Determination of phosphate incorporation shows that several proteins become hyperphosphorylated following addition of the compound. Which of the following statements would most accurately reflect these changes?

A) glycogen phosphorylase activity will be increased
B) PFK1 activity will be unaffected
C) PFK2 will exhibit an increased level of kinase activity
D) phosphorylase kinase activity will be decreased
E phosphoprotein phosphatase-1 activity will be increased

Answer 2

glycogen phosphorylase activity will be increased

Question 3

You are treating an 11-year-old female type 1 diabetic patient who forgot to eat after she self-administered her afternoon insulin. Blood work demonstrates that her serum glucose level is 1 mM (18mg/dL).
Which of the following statements correctly defines the metabolic situation in this patient?

A) a reversal of the muscle hexokinase reaction converts glucose 6-phosphate to glucose for oxidation in glycolysis
B) hepatic glycogen releases glucose in response to insulin-mediated dephosphorylation of glycogen phosphorylase
C) hepatic glycogen releases glucose through a reversal of the glycogen synthase reaction
D) phosphorylation of hepatic glycogen synthase prevents glucose incorporation into glycogen
E) the activity of muscle glycolysis is inhibited by the phosphorylation of PFK1

Answer 3

phosphorylation of hepatic glycogen synthase prevents glucose incorporation into glycogen

Question 4

You have been studying a cell line derived from a muscle tumor and comparing its activities, with respect to the effects of high levels of fatty acids on glucose oxidation, to those of normal skeletal muscle cells from the same individual. You find that exposing the normal cells to high levels of free fatty acids results in impaired levels of glucose oxidation. These results are expected based upon the interactions of the glucose-fatty acid cycle. However, the tumor-derived cells do not exhibit reduced glycolysis in the presence of high levels of free fatty acids. Which of the following best explains these observations?

A) the tumor cells contain a mutant form of acetylCoA carboxylase, which is insensitive to citrate resulting in reduced conversion of acetyl-CoA to malonyl-CoA and the acetyl-CoA then activates phosphoenolpyruvate carboxykinase
B) the tumor cells contain a mutant form of carnitine palmitoyltransferase 1, which restricts mitochondrial uptake of fatty acids which then build up in the cytosol leading to allosteric inhibition of PFK1
C) the tumor cells contain a mutant form of PFK1 which is insensitive to allosteric activation by fructose-2,6-bisphophate
D) the tumor cells contain a mutant form of PFK1 which is insensitive to allosteric inhibition by citrate
E) the tumor cells contain a mutant more active form of ATP-citrate lyase, causing significant reductions in mitochondrial citrate resulting in loss of citrate-mediated inhibition of PFK1

Question 5

You are studying the effects of an experimental compound on the process of glucose metabolism in laboratory animals. Addition of the compound to the animal chow is associated with decreased glucose output by the liver of these animals. Analysis of liver biopsy cells isolated 2-days following compound addition indicates that citrate transport into the cytosol is impaired. The activity of which of the following glycolytic enzymes is most likely to be affected by your experimental compound?

A) glyceraldehyde-3-phosphate dehydrogenase
B) 6-phosphofructo-1 kinase, PFK1
C) 6-phosphofructo-2 kinase, PFK2
D) phosphoglycerate kinase
E) pyruvate kinase

Question 6

Under conditions of anaerobic glycolysis, the NAD₊ required by glyceraldehyde-3-phosphate dehydrogenase is supplied by a reaction catalyzed by which of the following enzymes?

A) glycerol-3-phosphate dehydrogenase
B) α-ketoglutarate dehydrogenase
C) lactate dehydrogenase
D) malate dehydrogenase
E) pyruvate dehydrogenase

Question 7

You are examining the regulatory control of glycolysis by addition of a novel compound to a hepatocyte cell culture system. Your studies demonstrate that addition of the compound decreases the kinase activity of PFK2 while simultaneously increasing the phosphatase activity of the enzyme. This response most closely reflects which of the following naturally occurring controls exerted on PFK2?

A) allosteric inhibition by insulin
B) dephosphorylation by the appropriate protein phosphatase
C) increased AMP concentrations
D) increased glucose 6-phosphate concentrations
E) phosphorylation by cAMP-dependent protein kinase (PKA)

Question 8

You are examining the regulatory control of glycolysis by addition of a novel compound to a hepatocyte cell culture system. You discover that addition of the compound results in an increased rate of ATP production from glucose while simultaneously reducing glucose output into the culture medium. Your experimental compound is most likely mimicking which of the following?

A) fructose 1,6-bisphosphate
B) fructose 2,6-bisphosphate
C) fructose 1-bisphosphate
D) glucose 6-bisphosphate
E) phosphoenolpyruvate

Question 9

You are examining the regulatory control of glycolysis by addition of a novel compound to a hepatocyte cell culture system. You discover that addition of the compound results in a decreased rate of ATP production from glucose while simultaneously increasing glucose output into the culture medium. Further studies demonstrate that the changes observed in your culture system with addition of the compound can be mimicked by altering the cytosolic levels of citrate. Your compound is most likely altering the rate of glycolysis
By which of the following mechanisms?

A) inhibiting phosphodiesterase, PDE
B) inhibiting 6-phosphofructo-1-kinase (PFK1)
C) inhibiting pyruvate kinase
D) stimulating PEPCK
E) stimulating 6-phosphofructo-1-kinase (PFK1)

Question 10

Cytosolic reducing equivalents (NADH) generated by glycolysis in the liver, enter the mitochondria for generation of ATP by which of the following processes?

A) active transport of NADH into the mitochondrion
B) passive diffusion of NADH into the mitochondrion
C) transfer of electrons from NADH to NADH reductase at the mitochondrial surface
D) transfer of electrons to oxaloacetate with transport of malate into the mitochondrion
E) transfer of electrons to pyruvate with transport of lactate into the mitochondrion

Question 11

You are examining the regulatory control of glycolysis by addition of a novel compound to a hepatocyte cell culture system. You discover that addition of the compound results in an increased rate of ATP production from glucose. Further studies demonstrate that the changes observed in your culture system with addition of the compound can be mimicked by a number of substances that activate the rate-limiting enzyme of glycolysis. Your compound is most likely altering the rate of glycolysis in a manner similar to all of which of the following?

A) AMP, citrate, and fructose 2,6-bisphosphate
B) AMP, inorganic phosphate, and fructose 2,6-bisphosphate
C) ATP, citrate, and inorganic phosphate
D) ATP, inorganic phosphate, and fructose 1,6-bisphosphate
E) inorganic phosphate, citrate, and fructose 2,6-bisphosphate

Question 12

You are examining the effects of various oxygen concentrations on cultures of erythrocytes. You find that at low O₂ pressures there is rapid depletion of a necessary intermediate in the glycolytic pathway. Further analysis of the cells you are culturing indicates that the activity of the lactate dehydrogenase in these cells is extremely low relative to what is expected. Under these hypoxic conditions, which of the following is the most likely rapidly depleted intermediate?

A) ADP
B) citrate
C) FAD
D) glucose 6-phosphate
E) NAD⁺

Question 13

You are studying the effects of the addition of a novel compound to the chow of laboratory animals on the overall rate of flux through glycolysis. You discover that when the animals consume the mcompound containing chow, there is an increase in glycolytic flux to pyruvate. Examination of serum hormone levels in these animals indicates a change in the ratios of several key regulators of glucose homeostasis. The consumption of the test compound most likely causes an increase in which of the following hormone ratios, thus best explaining the observed changes in the rate of glycolysis?

A) cortisol to insulin
B) epinephrine to glucagon
C) glucagon to epinephrine
D) insulin to glucagon
E) insulin to cortisol

Question 14

In the production of ATP during glucose metabolism in erythrocytes, which of the following is the immediate donor of the phosphoryl group to ADP?

A) 2,3-bisphosphoglycerate
B) fructose 1,6-bisphosphate
C) fructose 2,6-bisphosphate
D) glyceraldehyde 3-phosphate
E) phosphoenolpyruvate

Question 15

You are studying the effects of the addition of a novel compound to the chow of laboratory animals on the overall rate of flux through glycolysis. You discover that when the animals consume the compound containing chow, there is an increase in glycolytic flux to pyruvate. Examination of cells from the livers of these animals demonstrates that when the compound enters the cells, it causes a rapid decrease in the ATP:ADP ratio. This effect most likely results in which of the following?

A) decreased isocitrate dehydrogenase activity
B) decreased phosphofructokinase-1 activity
C) decreased rate of electron transport
D) increased glycogen synthase activity
E) increased glycolytic pathway flux

Question 16

A healthy 28-year-old woman exhibits a peak serum glucose concentration of 220 mg/dL within 30 minutes of the consumption of 75 g of glucose. Two hours after ingestion, her serum glucose concentration decreases to 100 mg/dL. The uptake and trapping of glucose within liver cells at high serum glucose concentrations is facilitated by which of the following enzymes?

A) galactokinase
B) glucokinase
C) phosphoenolpyruvate carboxykinase (PEPCK)
D) phosphofructokinase-1 (PFK1)
E) pyruvate dehydrogenase

Question 17

The hydrolysis of which of the following compounds is characterized by a standard free energy change (ΔG_0′) that is more negative than that for the reaction: ATP → ADP + P_i?

A) glucose 1-phopsphate
B) glucose 6-phosphate
C) glycerol 1-phosphate
D) phosphoenolpyruvate
E) 3-phosphoglycerate

Question 18

The Warburg effect states that cancer cells carry out glucose metabolism in a manner distinct from the glycolytic process of cells in normal tissues. Cancer cells tend to "ferment" glucose into lactate even in the presence of sufficient oxygen to support mitochondrial oxidative phosphorylation. Which of the following enzymes is most responsible for the observations accounting for the Warburg effect?

A) glucokinase
B) glyceraldehyde-3-phosphate dehydrogenase
C) PFK1
D) PFK2
E) pyruvate kinase

Question 19

You are studying the effects of the addition of a novel compound to the chow of laboratory animals on the overall rate of flux through glycolysis in skeletal muscle. You discover that when the animals consume the compound containing chow, there is a decrease in glycolytic flux to pyruvate while at the same time there is increased glucose output to the blood. Cells isolated from muscle biopsy tissue from these animals respond to addition of the compound with a dramatic rise in the levels of cAMP. Given this effect of the compound, which of the following will occur first?

A) binding to the regulatory subunits of cAMPdependent protein kinase, PKA
B) desensitization of the catecholamine receptor
C) dissociation of the G protein into the a and bg components
D) increase in cytosolic Ca2+
E) inhibition of glycogen synthase

Question 20

A 9-month-old child is presented to the emergency room by his parents who report that he has been vomiting and has severe diarrhea. The episodes of vomiting began when the parents started feeding their child cow's milk. The infant exhibits signs of failure to thrive, weight loss, hepatomegaly, and jaundice. Laboratory tests show elevated blood galactose, hypergalactosuria, and metabolic acidosis with coagulation deficiency. These clinical and laboratory findings are most consistent with a deficiency in which of the following enzymes?

A) aldolase B
B) fructokinase
C) fructose-1,6-bisphosphatase
D) glucose-6-phosphate dehydrogenase
E) UDP-galactose uridyltransferase (GALT)

Question 21

Prolonged ethanol consumption and subsequent metabolism ultimately leads to a condition referred to as steatohepatitis or more commonly, "fatty liver syndrome." Ethanol metabolism results in alteration in the activity of which of the following enzymes, one of the consequences of which is excess lipid deposition in the liver?

A) fatty acyl-CoA oxidase
B) glucose-6-phosphate dehydrogenase
C) glycerol-3-phosphate dehydrogenase
D) lactate dehydrogenase
E) pyruvate dehydrogenase

Question 22

You are tending to a teenage patient following a reported suicide attempt. The teen ingested rat poison and has diarrhea and severe vomiting which has resulted in hypovolemic shock. Outward signs include a strong odor of garlic on the patient's breath. Which of the following is the most likely action of the toxic substance in the rat poison resulting in the observed symptoms?

A) it activates pyruvate dehydrogenase
B) it enhances the rate of gluconeogenesis
C) it increases glutathione production
D) it inhibits pyruvate dehydrogenase
E) it reduces the concentration of pyruvate

Question 23

In patients with suspected metastatic cancer in the brain, a useful diagnostic is positron emission tomography, PET. This technique utilizes a radioactive form of glucose that cannot be metabolized but is rapidly taken up by cancer cells due to their high rates of metabolism. Which of the following is most responsible for the rapid uptake of this compound into the tumor cells in the brain?

A) GLUT2
B) GLUT3
C) GLUT4
D) insulin
E) PFK1

Question 24

You are carrying out in vitro studies of skeletal muscle cell metabolism utilizing primary cultures of myocytes prepared from rectus femoris biopsies. Your studies involve the comparison of metabolic byproducts from carbohydrate metabolism under aerobic and anaerobic conditions. When your cell culture conditions allow for aerobic metabolism, which of the following compounds would be expected to be derived from any pyruvate generated from glycolysis?

A) acetyl-CoA
B) alanine
C) ethanol
D) lactate
E) oxaloacetate

Question 25

A 27-year-old man complains of intermittent right upper quadrant pain that extends to the inferior tip of his scapula. Analysis of blood reveals mild anemia with the presence of normocytic and normochromic nonsperical erythrocytes. Additional blood work shows elevated levels of glucose 6-phosphate (G6P) and 2,3-bisphosphoglycerate (2,3BPG). Ultrasonic examination of the abdomen shows cholelithiasis. Following removal of her gallbladder, the stones are examined and shown to contain bilirubin. A deficiency in which of the following enzymes would most explain the signs and symptoms in this patient?

A) glucose 6-phosphate dehydrogenase
B) PFK1
C) pyruvate carboxylase
D) pyruvate dehydrogenase
E) pyruvate kinase