USMLE USMLE Certifications USMLE-STEP-1 Questions & Answers

• Question 551:

  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?

  A. decreased glycogen phosphorylase kinase activity due to an increase in calcium binding to its calmodulin subunit

  B. decreased phosphorylation of, and inhibited activity of glycogen phosphorylase kinase

  C. increased glycogen phosphorylase kinase activity due to an activation of phosphoprotein phosphatase

  D. increased glycogen phosphorylase kinase activity due to an increase in calcium binding to its calmodulin subunit

  E. increased phosphorylation of, and inhibited activity of glycogen phosphorylase kinase

  Correct Answer: D

  Section: Biochemistry 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).

• Question 552:

  Which of the following correctly defines the term: p ?

  

  A. equilibrium constant for the dissociation of HA to and

  B. ion constant of water

  C. negative log of the concentration of

  D. pH at which a molecule is neutrally charged

  E. pH at which an equivalent distribution of acid and conjugate base exist in solution

  Correct Answer: E

• Question 553:

  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?

  A. glucose-6-phosphatase activity in the microsomes

  B. microsomal glucose-6-phosphate transporter

  C. cytosolic glucose-6-phosphatase

  D. microsomal glucose transport

  E. microsomal phosphate transporter

  Correct Answer: B

• Question 554:

  An individual harboring a mutation in ornithine transcarbamoylase (OTC) would be expected to exhibit which of the following measurable abnormalities?

  A. citrullinemia

  B. elevated urinary excretion of argininosuccinic acid

  C. elevation in blood orotic acid

  D. excess production of foam cells

  E. uric acid deposition in the joints

  Correct Answer: C

  Section: Biochemistry A deficiency in OTC results in one of the urea cycle defect diseases, which are the major causes of hyperammonemia in the newborn. Differentiation of which urea cycle enzyme is defective and causing the hyperammonemia can be accomplished by analysis of the levels of the various intermediates in the cycle (see below figure for UCD DDx).

  

  Adefect in OTC prevents incorporation of carbamoylphosphate into ornithine (see below figure). The carbamoylphosphate will diffuse out of the mitochondria and serve as a precursor for the synthesis of the pyrimidine nucleotides in excess of need leading to an elevation of orotic acid (pyrimidine intermediate) in the blood. A deficiency of the urea cycle enzyme, ASD, will lead to citrullinemia (choice A). Elevation in excretion of argininosuccinate (choice B) will result from a deficiency in the urea cycle enzyme, arginosuccinase. Foam cells are lipidladen cells that are characteristic of disorders in lipid etabolism such as that seen in NPD, which is caused by a deficiency in sphingomyelinase. Uric acid deposition (choice E) results from excess catabolism of the purine nucleotides.

• Question 555:

  Which of the following is the hypophyseotropic hormone that regulates the activity of the lactotrophs of the anterior pituitary?

  A. CRH

  B. GnRH

  C. growth hormone-releasing hormone (GRH)

  D. prolactin-releasing factor (PRF)

  E. thyrotropin-releasing hormone (TRH)

  Correct Answer: D

  Section: Biochemistry The lactotrophs of the anterior pituitary secrete prolactin in response to the action of PRF. Corticotropinreleasing hormone, CRH (choice A) regulates primarily the secretion of ACTH, but also other products of the ACTH precursor protein, pro-opiomelanocortin, POMC. GnRH (choice B) controls the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gonadotrophs. GRH (choice C) stimulates growth hormone secretion from pituitary somatotrophs. TRH (choice E) stimulates the thyrotropes to secrete thyroid-stimulating hormone, TSH (also called thyrotropin).

• Question 556:

  Lipoprotein lipase (LPL) is the endothelial cellassociated enzyme necessary for release of fatty acids from circulating lipoproteins. Which of the following apolipoproteins is required to activate LPL- mediated release of fatty acids from chylomicrons?

  A. apo A

  B. apo

  C. apo

  D. apo CII

  E. apo E

  Correct Answer: D

• Question 557:

  As a hypothetical approach to treating the hyperglycemia associated with Type II diabetes, a drug firm proposes to develop an inhibitor of liver glycogen phosphorylase. What is the biochemical rationale for this approach to inducing hypoglycemia?

  A. Hepatic fatty acid oxidation will decrease leading to reduced energy production needed for gluconeogenesis.

  B. Hepatocytes will have a reduced capacity to store glucose following meals.

  C. Liver glucose output will be reduced early during fasting.

  D. The resultant increase in glycogen storage will inhibit glucose uptake by the liver, leading to increased usage in skeletal muscle.

  E. There will be an increase in hepatic gluconeogenesis.

  Correct Answer: C

  Section: Biochemistry During early fasting, as the level of glucose in the blood falls, the pancreas releases glucagon into the circulation to counter this drop. The major site of glucagon action is the liver. There it induces the activity of the glycogen phosphorylase leading to an increase in glucose release from glycogen stores. Thus, an inhibition of glycogen phsphorylase would limit the ability of the liver to provide glucose to the blood. Negatively affecting the activity of glycogen phosphorylase would not significantly affect the rate of hepatic fatty acid oxidation (choice A), skeletal muscle glucose usage (choice D), nor hepatic gluconeogenesis (choice E). The liver may have a reduced capacity for de novo storage of glucose following meals (choice B) due to a prior reduction in the release of glucose via the inhibition of glycogen phosphorylase; however, on fasting there would still be a reduction in glucose release.

• Question 558:

  A2-month-old infant suffering from increased vomiting and diarrhea is seen in the hospital and observed to have significant abdominal distention due to hepatosplenomegaly. Unfortunately, the infant does not survive. Autopsy reveals calcification of the adrenals and massive accumulation of cholesteryl esters and triglycerides in most tissues. Analysis of enzyme activity in fibroblasts and lymphocytes demonstrates a significant acid lipase (cholesteryl ester hydrolase) deficiency. These clinical findings are indicative of which of the following disorders?

  A. hyperlipoproteinemia, type I (familial liproprotein lipase deficiency)

  B. I-cell disease (mucolipidosis type II)

  C. Maroteaux-Lamy syndrome

  D. Sanfilippo syndrome

  E. Wolman disease

  Correct Answer: E

  Section: Biochemistry Wolman disease results from a deficiency in the lysosomal acid lipase enzyme (also called cholesteryl ester hydrolase) and is very nearly always a fatal disease of infancy. Symptoms of the disorder arise from massive accumulation of cholesteryl esters and triglycerides in most tissues. Clinical manifestations include hepatosplenomegaly leading to abdominal distention, GI abnormalities, steatorrhea, and adrenal calcification. Type I hyperlipoproteinemia (choice A) results from a deficiency in LPL activity. LPL is the enzyme found on the surface of vessel endothelial cells and is responsible for hydrolyzing fatty acids from the triglycerides found in circulating liporpotein particles. This action allows cells to get fatty acids for energy production from lipoproteins in the plasma. This disoder leads to massive accumulation of chylomicrons and triglycerides in the plasma. Symptoms associated with type I hyperlipoproteinemia are usually detected in childhood and include eruptive cutaneous xanthomatosis, hepatosplenomegaly, and repeated episodes of abdominal pain. I-cell disease (choice B) results from a deficiency in the targeting of lysosomal enzymes to the lysosomes. Affected cells have dense inclusion bodies filled with storage material, hence the derivation of the disease name. There are elevated levels of lysosomal enzymes in the plasma and body fluids of I-cell patients. Symptoms include severe psychomotor retardation, coarse facial features, and severe skeletal abnormalities. The rapidly progressing disease can lead to death between 5 and 8 years of age. Maroteaux- Lamy syndrome (choice C) results from a defect in the enzyme Nacetylgalactosamine-4-sulfatase (arylsulfatase B) responsible for the catabolism of complex glycosaminoglycans. There are three distinct forms of Maroteax-Lamy syndrome that range in severity. Symptoms include coarse facial features, skeletal abnormalities corneal clouding, and aortic valve disruption. Sanfillipo syndrome (choice D) comprises at least four distinct genetic defects that result from deficiencies in enzymes required for the catabolism of complex glycosaminoglycans of the heparan sulfate class. In all cases, the clinical symptoms are similar and include severe mental deterioration, hyperactivity, and disorders in the skin, lungs, heart, and skeletal muscle.

• Question 559:

  Obesity, genetic profile, and aging all contribute to the development of Type II diabetes. Of the following, which is the most important additive factor for these three conditions in the development of Type II diabetes?

  A. elevated hepatic ketogenesis

  B. elevated pancreatic glucagon secretion

  C. impaired renal clearance of glucose

  D. increased adipose tissue activity leading to hyperlipidemia

  E. muscle resistance to insulin

  Correct Answer: E

  Section: Biochemistry The influence of obesity, genetic profile, and age on overall metabolism is most significant at the level of skeletal muscle sensitivity to the actions of insulin (below figure). Due to the overall mass of skeletal muscle in the body, the uptake of glucose by this tissue, and consequently its role in blood glucose homeostasis, is a significant factor in insulin responses. Progressive loss of skeletal muscle sensitivity to insulin leads to increased rates of visceral cell lipolysis and pancreatic beta-cell compensation. Eventually, the pancreas can no longer continue compensating for impaired insulin responses and pancreatic beta-cell decompensation occurs, further exacerbating the problem. The disrupted insulin response leads to increased hepatic gluconeogenesis, which further increases circulating glucose levels. The overall outcome of these reposnses is development of progressisely worsening Type II diabetes. Whereas, each of the other options (choices AD) will ensue due to impaired insulin responses in skeletal muscle, none is significant in the development of diabetes.

• Question 560:

  Amale infant, delivered at 38 weeks' gestation, presents with severe bowing of long bones, blue sclera, and craniotabes at birth. Radiographs show severe generalized osteoporosis, broad and crumpled long bones, beading ribs, and a poorly mineralized skull. Histologic examination of the long bones revealed the trabecula of the calcified cartilage with an abnormally thin layer of osteoid, and the bony trabeculae are thin and basophilic. The symptoms observed in the infant are characteristic of which disease?

  A. Ehlers-Danlos syndrome

  B. Marfan syndrome

  C. occipital horn syndrome

  D. osteogenesis imperfect

  E. scurvy

  Correct Answer: D

  Section: Biochemistry Osteogenesis imperfecta consists of a group of at least four types (mild, extensive, severe, and variable). The disorder is characterized by brittle bones and abnormally thin sclerae, which appear blue owing to the lack of connective tissue. The symptoms arise due to defects in two alpha-collagen genes, the COL1A1 and COL1A2 genes. There have been over 100 mutations identified in these two genes. The mutations lead to decreased expression of collagen or abnormal pro1 proteins. The abnormal proteins associate with normal collagen subunits, which prevents the triple helical structure of normal collagen to form. Theresult is degradation of all the collagen proteins, both normal and abnormal. Ehlers-Danlos syndrome (choice A) comprises at least 10 defined types of a related disorder. Characteristic clinical features are easy bruising, markedly soft hyperextensible skin, extreme joint hypermobility, and the formation of thin, atrophic, "cigarette-paper" scarring following injury. Marfan syndrome (choice B) results in cardiovascular, musculoskeletal, and ophthalmic abnormalities. Hallmark clinical manifestations are aortic dilation, mitral valve prolapse, dissecting aneurysms, arachnodactyly, and ectopia lentis. Occipital horn syndrome (choice C), a disorder that manifests with symptoms similar to other collagen metabolism disorders, results from defects in copper metabolism. Clinical features include loose skin and joints, hernias, and abnormally shaped bones. Scurvy (choice E), which is caused by a deficiency in vitamin C, is characterized by decreased wound healing and hemorrhaging, anemia, osteoporosis, soft swollen gums, and easily bruised skin.