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Free STEP1 Exam Braindumps (page: 76)

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You are examining the biochemical characteristics of the liver dysfunction in your patient, who is exhibiting signs of a glycogen storage disease. You have isolated the microsomal fraction (contains the endoplasmic reticulum) of a liver biopsy homogenate from your patient and a control individual for your studies. Incubation with radioactive phosphate-labeled glucose-6-phosphate results in an increase in isotope associated with the microsomes from your control sample but no increase in association with the microsomes from your patient. These results are best explained by a defect in which of the following?

  1. glucose-6-phosphatase activity in the microsomes
  2. microsomal glucose-6-phosphate transporter
  3. cytosolic glucose-6-phosphatase
  4. microsomal glucose transport
  5. microsomal phosphate transporter

Answer(s): B

Explanation:

The patient is suffering from von Gierke disease, which is glycogen storage disease type I. This disease results from one of several defects in the process of dephosphorylating glucose-6- phosphate to free glucose and the pathways are shown in below figure.

The actual dephosphorylation takes place within the lumen of the ER where glucose-6-phosphatase resides, embedded in the membrane. Thus, glucose-6- phosphate must first be transported into the ER to be acted on by glucose- -phosphatase. Following dephosphorylation, the free glucose is then transported back out to the cytosol. In addition, the released inorganic phosphate (Pi) must also be transported to the cytosol. Because of this pathway and the multiple activities involved, there have been four distinct subtypes of this particular glycogen storage disease identified. Type Ia results from deficiencies in glucose-6- phosphatase, type Ib from deficiencies in the glucose-6-phosphate transporter, type Ic from deficiencies in the transporter, and type Id from deficiencies in GLUT7, which is the glucose transporter in the membrane of the ER. When the ER is isolated (microsomal fraction) from cells and incubated with radiolabeld glucose-6-phosphate, there will be uptake of the label into the membranes only if the activity of the glucose-6-phosphate transporter is unaffected. Because the microsomes from the patient failed to take up the label, the data indicates the individual has a defect in the glucose-6-phosphate transporter and is suffering from type Ib glycogen storage disease. A deficiency in glucose-6-phosphatase (choice A) would not prevent uptake by the microsomes. Glucose- 6-phosphatase is not found in the cytosol (choice C). Deficiencies in the microsomal GLUT7 (choice D) or the Pi transporter (choice E) would lead to failure to take up the radio-labeled glucose.



Which of the following correctly defines the term: p ?

  1. equilibrium constant for the dissociation of HA to and
  2. ion constant of water
  3. negative log of the concentration of
  4. pH at which a molecule is neutrally charged
  5. pH at which an equivalent distribution of acid and conjugate base exist in solution

Answer(s): E

Explanation:

The term pKa defines the pH at which an equivalent distribution of acid and conjugate base (or base and conjugate acid) exists in solution. This term is derived from the equation demonstrating that pH = + log[ ]/ [HA]. At the point of the dissociation where the concentration of the conjugate base [ ] is equal to that of the acid [HA] the value of [ ]/[HA] is equal to 1 and the log of 1 is 0, therefore, at this point in a dissociation is equal to pH. The equilibrium constant for the dissociation of an acid (or base) is (choice A). The ion constant for water (choice B) is defined as
. The negative log of the hydrogen ion concentration [ ] (choice C) is pH. The pH at which a
molecule or compound is electrically neutral (choice D) is called the isoelectric point, pI.



Muscle membrane will depolarize in response to acetylcholine binding its receptors at the neuromuscular junction. Associated with this depolarization are changes in glycogen metabolism in skeletal muscle cells. Which of the following represents the correct changes in enzyme activity seen in response to acetylcholine binding?

  1. decreased glycogen phosphorylase kinase activity due to an increase in calcium binding to its calmodulin subunit
  2. decreased phosphorylation of, and inhibited activity of glycogen phosphorylase kinase
  3. increased glycogen phosphorylase kinase activity due to an activation of phosphoprotein phosphatase
  4. increased glycogen phosphorylase kinase activity due to an increase in calcium binding to its calmodulin subunit
  5. increased phosphorylation of, and inhibited activity of glycogen phosphorylase kinase

Answer(s): D

Explanation:

The binding of acetylcholine to its receptor at the neuromuscular junction results in depolarization of the muscle membrane. This event triggers the release of calcium ions from the sarcoplasmic reticulum. The increase in intracellular calcium concentration leads to many changes in enzyme activity. One effect of calcium is that it is bound by various calciumregulated binding proteins. One of the subunits of glycogen phosphorylase kinase is calmodulin, a calcium-binding protein. The interaction of calcium with calmodulin alters the conformation of calmodulin, which leads to an activation of glycogen phosphorylase kinase activity in the absence of phosphorylation. The activity of glycogen phosphorylase kinase is increased not decreased (choice A) by calcium interaction with calmodulin present in the enzyme complex. Increases in intracellular calcium (as in response to acetylcholine binding at the neuromuscular junction) do not affect the level of phosphorylation of glycogen phosphorylase kinase (choices B and E) nor does it affect the activity of phosphoprotein phosphatase (choice C).



A 42-year-old man presents with hepatomegaly, jaundice, refractory ascites, and renal insufficiency. Peripheral leukocytes exhibit only 20% of normal glucocerebrosidase activity. Which of the following would explain his symptoms?

  1. Fabry disease
  2. Gaucher disease
  3. Krabbe disease
  4. Niemann-Pick disease type II C
  5. Tay-Sachs disease

Answer(s): B

Explanation:

Numerous severe disorders are associated with the inability to properly degrade the complex carbohydrate moieties of glycosaminoglycans, proteoglycans, and glycoproteins. These disorders fall into a broad category of diseases termed the lysosomal storage diseases. Several of the lysosomal storage diseases result in hepatosplenomegaly, renal dysfunction, and skeletal defects, and therefore these symptoms are not diagnostic in themselves of a particular lysosomal storage disease, but only indicative of such disorders. However, disorders such as NPD (choice D) and Tay-Sachs disease (choice E) are of such severity that early childhood mortality occurs and thus would not present in a 42- year-old patient. It is necessary to evaluate enzyme function in skin fibroblasts or white cells of the blood. Gaucher disease is caused by a defect in glucocerebrosidase activity and hence an assayable decrease in the activity of this enzyme would be diagnostic of this disease. Fabry disease (choice A) results from a defect in alpha- galactosidase A. Krabbe disease (choice C) results from a defect in galactocerebrosidase. Based on genetic linkage analyses as well as enzyme studies and the characterization of accumulating lysosomal substances, NPD (choice D) should be divided into type I and type II; type I has two subtypes, A and B (NPA and NPB), which show deficiency of acid sphingomyelinase. NPD type II likewise has two subtypes, types C1 and C2 (NPC) and type D (NPD), both of which show accumulation of abnormal LDL-cholesterol.
The NPC1 gene contains regions of homology to mediators of cholesterol homeostasis suggesting why LDL-cholesterol accumulates in lysosomes of afflicted individuals. Tay-Sachs disease (choice E) results from a defect in hexosaminidase A.






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