USMLE USMLE Certifications USMLE-STEP-1 Questions & Answers

• Question 581:

  Clinical evidence indicates aspirin is effective in the control of numerous chronic conditions such as atherosclerosis. The principal cardiovascular benefit from aspirin is due to its ability to reduce the incidence and severity of thrombotic episodes. The anticoagulant effect of aspirin occurs through its ability to inhibit which of the following activities?

  A. cyclooxygenase

  B. fibrin cross-linking by factor XIIIa

  C. phospholipase

  D. thrombin binding to activated platelets

  E. von Willebrand factor

  Correct Answer: A

• Question 582:

  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-PFK-1

  Correct Answer: C

  Section: Biochemistry Essential fructosuria is an autosomal recessive disorder manifesting benign asymptomology due to a lack of fructokinase. The principal clinical signs of essential fructosuria are hyper-fructosemia and fructosuria. Deficiency in aldolase B (choice A) results in the clinically severe disorder, hereditary fructose intolerance. Symptoms include severe hypoglycemia and vomiting after ingestion of fructose. Prolonged fructose ingestion by infants with this disorder will lead to poor feeding, hepatomegaly, vomiting, jaundice, and eventually hepatic failure and death. Aldolase A deficiency (choice B) is very rare and has only been observed associated with erythrocytes and fibroblasts and leads to hemolytic anemia. Hexokinase deficiency (choice D) is also rare and associated with erythrocyte disfuction leading to chronic hemolytic anemia. Deficiency in PFK-1 (choice E) results in the glycogen storage disease known as Tarui disease. Symptoms of PFK-1 deficiency include exercise-induced cramping and pain, myoglobinuria, and hemolytic anemia.

• Question 583:

  The statin class of drugs that are currently used to control hypercholesterolemia function to lower circulating levels of cholesterol by which of the following mechanisms?

  A. increasing the elimination of bile acids, leading to increased diversion of cholesterol into bile acid production

  B. increasing the synthesis of apolipoprotein B-100 (apo ), resulting in increased elimination of cholesterol through the action of low-density lipoprotein (LDL) uptake by the liver

  C. decreasing the absorption of dietary cholesterol from the intestines

  D. inhibiting the interaction of LDLs with the hepatic LDL receptor

  E. inhibiting the rate-limiting step in cholesterol biosynthesis

  Correct Answer: E

  Section: Biochemistry

  The statin class of cholesterol-lowering drugs all exert their effects on the activity of HMG-CoA reductase.

  This enzyme carries out the rate-limiting step in cholesterol biosynthesis. The cholestyramine-based resins

  are used therapeutically to bind up intestinal bile salts, which increases the excretion of bile (choice A).

  The net effect of increased bile excretion is increased diversion of cholesterol into bile acid synthesis,

  thereby lowering circulating cholesterol levels. No current therapy targets synthesis of apolipoprotein

  synthesis (choice B), decreasing intestinal absorption of cholesterol (choice C), or inhibition of LDL-

  receptor interactions (choice D).

• Question 584:

  The rate-limiting step in glycolysis occurs at the step catalyzed by which of the following enzymes?

  A. glyceraldehyde-3-phosphate dehydrogenase

  B. 6-phosphofructo-1 kinase, PFK-1

  C. 6-PFK-2

  D. phosphoglycerate kinase

  E. pyruvate kinase

  Correct Answer: B

  Section: Biochemistry There are three reactions of glycolysis that are thermodynamically irreversible. These are the hexokinase (glucokinase), PFK-1, and PKcatalyzed reactions. Reactions that are essentially irreversible in most metabolic pathways are subject to complex regulatory controls and represent rate-limiting steps in the pathway. The primary site of regulation of glycolysis occurs at the level of the PFK-1-catalyzed step. Hence, this reaction is the rate-limiting step in glycolysis. PFK-1 is subject to allosteric control by numerous compounds. Citrate and ATP inhibit the activity of PFK-1, while AMP and fructose 2,6bisphosphate (F2,6- BP) activate the enzyme. The principal control of PFK-1 activity is exerted by alterations in the level of F2,6- BP. This compound is synthesized from fructose-6-phosphate by the bifunctional enzyme, PFK-2/fructose- 2,6-bisphosphatase (PFK-2/F2,6-BPase). PFK-2 (choice C) contains two catalytic domains, one a kinase and the other a phosphatase, the activities of which are affected by the state of phosphorylation. The phosphatase domain is active when the enzyme is phosphorylated and converts F2,6-BP back to F6-P, thereby reducing the levels of this powerful activator of PFK-1. Thus, although the activity of PFK-2 will determine the rate of activity of PFK-1, it is itself not the rate-limiting enzyme in glycolysis. Glyceraldehyde- 3-phosphate dehydrogenase (choice A) and PGK (choice D) are not regulated enzymes of glycolysis. PK (choice E) is regulated during glycolysis, but does not constitute a rate-limiting step.

• Question 585:

  Which of the following peptide hormones is released in response to stimulation of pituitary gonadotropes?

  A. ACTH

  B. follicle-stimulating hormone

  C. growth hormone

  D. prolactin

  E. thyroid-stimulating hormone

  Correct Answer: B

  Section: Biochemistry The pituitary gonadotrophs are cells that secrete the gonadotrophic peptide hormones, follicle- stimulating hormone (FSH), and leutinizing hormone (LH). FSH acts on Sertoli cells of the testis inducing androgen-binding protein synthesis, which maintains a high concentration of testosterone in tubules increasing spermatogenesis. In the ovary, FSH stimulates aromatase activity in the granulose cells stimulating ovum maturation and estradiol production. Pituitary orticotrophs are the ACTH- secreting cells (choice A), somatotrophs secrete growth hormone (choice C), lactotrophs secrete prolactin (choice D), and thyrotrophs secrete thyroid-stimulating hormone (choice E).

• Question 586:

  There is but a single enzyme-catalyzed reaction in the human body known to generate carbon monoxide (CO) as one of its products. Which of the following enzymes represents the one that catalyzes this CO-producing reaction?

  A. biliverdin reductase

  B. coproporphyrinogen oxidase

  C. heme oxygenase

  D. protoporphyrinogen oxidase

  E. uroporphyrinogen decarboxylase

  Correct Answer: C

• Question 587:

  An infant admitted to the emergency room has been found to be suffering from ammonia intoxication, which was verified by measurement of an elevation of N + in the serum. Treatment of this infant

  

  with arginine results in a reduction serum N + and a lessening of the effects of the ammonia

  

  toxicity. The ability of arginine to render this effect stems from its role in the synthesis of an allosteric activator of the the urea cycle enzyme, carbamoylphosphate synthetase-I (CPS-I). Which of the following represents this potent allosteric effector of CPS-I?

  A. argininosuccinate

  B. bicarbonate ion

  C. fumarate

  D. N-acetylcysteine E. N-acetylglutamate

  Correct Answer: E

  Section: Biochemistry CPS-I is absolutely dependent on the allosteric effector N-acetylglutamate for its activity. This allosteric effector is synthsized by the enzymeN-acetylglutamate synthetase, which is activated by the urea cycle amino acid arginine. None of the other compunds (choices A, B, C, and D) have any effect on CPS-I activity.

• Question 588:

  In a comparative study of two related cell lines, you find that one responds normally to insulin while the other has an impaired response. You discover that both cell lines bind insulin with equal affinity but that the impaired response is manifest in an inability to recruit the insulin response substrate-1 (IRS-1) protein to the receptor. This would most likely be due to which of the following?

  A. inability of the receptor to phosphorylate the RAS G-protein

  B. loss of activation of phospholipase C-gamma (PLC-g)

  C. mutation in the tyrosine phosphorylation site of IRS

  D. serine phosphorylation of the insulin receptor preventing IRS binding

  E. tyrosine phosphorylation of the insulin receptor leading to the loss of the IRS binding site

  Correct Answer: C

  Section: Biochemistry Many causes of insulin-resistance are due to defects that occur in events of the insulininduced signaling cascade, which takes place after insulin binds to its receptor. All of the postreceptor responses initiated by insulin binding to its receptor are mediated as a consequence of the activation of several signal transduction pathways that require tyrosine phosphorylation of sites in the intracellular portion of the receptor. These include receptor activation of PI3K. Activation of PI3K involves a linkage to receptor activation of insulin receptor substrates (of which there are four: IRS-1, IRS-2, IRS-3, and IRS-4). Activated PI3K phosphorylates membrane phospholipids, the major product being phosphotidylinositol 3,4,5trisphosphate, PIP3. PIP3 in turn activates the enzymes protein kinase B, PKB (also called Akt), PIP3dependent kinase (PDK), some isoforms of PKC, principally PKC-l, and small ribosomal subunit protein 6 kinase, S6K. The mitogen-activated protein (MAP) kinase pathway is also activated either through receptor activation of the protein tyrosine phosphatase (Shp-2) or growth factor receptor- binding protein-2 (Grb2). With respect to insulin responses, activation of PKB and PKC-l leads to translocation of GLUT4 molecules to the cell surface. resulting in increased glucose uptake which is significant in skeletal muscle. Activation of PKB also leads to the phosphorylation and activation of GSK3, which is a major regulatory kinase of glycogen homeostasis. In addition, PKB phosphorylates and inhibits the activity of a transcription factor (FKHRL1) that has proapoptotic activity. This results in reduced apoptosis in response to insulin action. Activation of S6K leads to the phosphorylation of the regulator of translation eIF-4E-binding protein, 4EBP. Phosphorylation of 4E-BP prevents it from binding to eIF-4E, the consequences of which would normally lead to a reduction in translation rate. Insulin also has profound effects on the transcription of numerous genes, effects that are primarily mediated by regulated function of sterol-regulated element-binding protein (SREBP). These transcriptional effects include (but are not limited to) increases in glucokinase, PK, LPL, FAS, and ACC and decreases in glucose-6-phosphatase, fructose-1,6bisphosphatase, and PEPCK. The insulin receptor does not phosphorylate the RAS gene product (choice A). Loss of activation of PLC-g (choice B) would not prevent IRS proteins from binding to the activated insulin receptor. Serine phosphorylation of the insulin receptor (choice D) is not involved in IRS binding. Tyrosine phosphorylation of the insulin receptor results in the formation of IRS binding sites, not in the loss (choice E) of such binding sites.

• Question 589:

  AIP is the major autosomal-dominant acute hepatic porphyria. This disease is caused by a deficiency in porphobilinogen (PBG) deaminase, an enzyme of heme biosynthesis. Patients afflicted with this disease would be expected to excrete excess amounts of which of the following?

  A. delta-aminolevulinic acid (ALA)

  B. coproporphyrinogen III

  C. hydroxymethylbilane

  D. protoporphyrin IX

  E. type III uroporphyrinogen

  Correct Answer: A

  Section: Biochemistry PBG deaminase (also called hydroxymethylbilane synthase) catalyzes the heme biosynthesis reaction involving the head-to-tail condensation of four molecules of PBG to produce the linear tetrapyrrole intermediate, hydroxymethylbilane. Hydroxymethylbilane can nonenzymatically cyclize into uroporphyrinogen I, which is why PBG deaminase is also known as uroporphyrinogen I synthase. ALA is the precursor for PBG, thus a defect in PBG deaminase would lead to excess ALA excretion. The compounds in choices BE all represent products of reactions that are downstream of PBG deaminase in the heme biosynthetic pathway and thus would not be excreted in high amounts in someone with AIP.

• Question 590:

  Interference with the action of angiotensinconverting enzyme (ACE) is an effective means at reducing elevations in blood pressure. The circulating concentration of which of the following hormones would be

  affected as a consequence of the use of ACE inhibitors?

  A. ACTH

  B. aldosterone

  C. corticotrophin-releasing hormone, CRH

  D. estradiol

  E. gonadotropin-releasing hormone, GnRH

  Correct Answer: B