Phosphoenolpyruvate carboxykinase (PEPCK) deficiency is a rare metabolic disorder. What are the likely symptoms of this disease?Group of answer choicesLow fasting blood glucose levels and lactate acidosisDecreased glycogen storage and low fasting blood glucose levelsIncreased glycogen storage and lactate acidosisHigh fasting blood glucose levels and lactate acidosis PreviousNext

Baker-Winegrad Disease is rare congenital disorder caused by a decrease in the activity of fructose-1,6-bisphosphatase. What are the likely symptoms of this disease?Group of answer choicesIncreased glycogen storage and lactate acidosisDecreased glycogen storage and low fasting blood glucose levelsHigh fasting blood glucose levels and lactate acidosisLow fasting blood glucose levels and lactate acidosis

Von Gierke’s and McArdle’s disease are two of the most common glycogen storage diseases.Which of the following statements are TRUE for these diseases? i) Von Gierke’s disease typically results from a mutation in glucose 6-phosphatase.ii) McArdle’s disease typically results from a mutation in glycogen phosphorylase.iii) McArdle’s disease typically results from a mutation in glucose 6-phosphatase.iv) Von Gierke’s disease typically results from a mutation in glycogen phosphorylase.v) Von Gierke’s disease patients cannot release glucose to the blood, have enlarged livers and kidneys and elevated lipids in the blood (hyperlipidaemia).vi) McArdle’s disease patients cannot release glucose to the blood, have enlarged livers and kidneys and elevated lipids in the blood (hyperlipidaemia).vii) McArdle’s disease patients suffer from severe muscle cramps with initial attempts of exercise, but these cramps subside with repeated attempts.viii) Von Gierke’s disease patients suffer from severe muscle cramps with initial attempts of exercise, but these cramps subside with repeated attempts.

A newborn girl is diagnosed with a rare genetic disorder that causes premature lysis of red blood cells.  Through genome sequencing, physicians identified a specific mutation (R510Q) in both copies of her pyruvate kinase gene, which encodes the enzyme that catalyzes the final step of glycolysis.  Pyruvate kinase produces pyruvate and ATP from phosphoenolpyruvate (PEP) and ADP.PEP + ADP → Pyruvate + ATPReaction 1Because red blood cells lack mitochondria, pyruvate in erythrocytes does not enter the citric acid cycle and the electron transport chain.  Therefore, red blood cells rely almost exclusively on glycolysis to produce sufficient ATP for cellular functions.  In patients with pyruvate kinase deficiency, a lack of ATP is believed to compromise the integrity of the red blood cell membrane, leading to premature lysis in the spleen.  Although these observations are well established, the exact mechanism by which low ATP alters the cell membrane is unclear.Scientists interested in analyzing this particular patient's gene variant expressed and purified recombinant R510Q pyruvate kinase.  They performed several biochemical tests to characterize the R510Q mutant with respect to wild-type (WT) pyruvate kinase.  In the first experiment, WT and R510Q pyruvate kinases were each incubated with a constant amount of ADP and varying amounts of PEP.  The activity of the enzyme was measured at each concentration of PEP and plotted.  They then repeated the experiment in the presence of ATP and found that ATP is a noncompetitive inhibitor of the WT enzyme but a mixed inhibitor of the R510Q enzyme.  The results are shown in Figure 1.  All experiments were performed using the same enzyme concentration.Figure 1  Pyruvate kinase activity with and without ATP as a function of [PEP].  Open markers are shown at ½Vmax for each plot.Adapted from Wang, C., Chiarelli, L.R., Bianchi, P., Abraham, D.J., Galizzi, A., Mattevi, A., Zanella, A., & Valentini, G. (2001). Human erythrocyte pyruvate kinase: characterization of the recombinant enzyme and a mutant form (R510Q) causing nonspherocytic hemolytic anemia. Blood, 98(10), 3113–3120. Question 45Scientists predict that gene copy number is proportional to protein expression for pyruvate kinase.  If this hypothesis is correct, which kinetic parameter would be expected to double when the gene copy number doubles?A.Catalytic efficiencyB.Maximum velocityC.Catalytic turnoverD.Equilibrium constant

Glycogen storage disease type I (GSD I) or von Gierke's disease, is the most common of the glycogen storage diseases. This genetic disease results from deficiency of the enzyme glucose-6-phosphatase.The metabolic outcomes of GSD I are likely to include :Group of answer choicesHigh blood glucose, decreased blood pH, decreased glycogen storage in liver and kidneysLow blood glucose, increased blood pH, decreased glycogen storage in liver and kidneysHigh blood glucose, increased blood pH, increased glycogen storage in liver and kidneysHigh blood glucose, decreased blood pH, increased glycogen storage in liver and kidneysLow blood glucose, increased blood pH, increased glycogen storage in liver and kidneysLow blood glucose, decreased blood pH, decreased glycogen storage in liver and kidneysHigh blood glucose, increased blood pH, decreased glycogen storage in liver and kidneysLow blood glucose, decreased blood pH, increased glycogen storage in liver and kidneys

Glycogen storage disease type I (GSD I) or von Gierke's disease, is the most common of the glycogen storage diseases. This genetic disease results from deficiency of the enzyme glucose-6-phosphatase.The metabolic outcomes of GSD I are likely to include :Group of answer choicesLow blood glucose, increased blood pH, increased glycogen storage in liver and kidneysLow blood glucose, decreased blood pH, increased glycogen storage in liver and kidneysHigh blood glucose, increased blood pH, decreased glycogen storage in liver and kidneysHigh blood glucose, increased blood pH, increased glycogen storage in liver and kidneysHigh blood glucose, decreased blood pH, decreased glycogen storage in liver and kidneysLow blood glucose, increased blood pH, decreased glycogen storage in liver and kidneysHigh blood glucose, decreased blood pH, increased glycogen storage in liver and kidneysLow blood glucose, decreased blood pH, decreased glycogen storage in liver and kidneys