USMLE USMLE Certifications USMLE-STEP-1 Questions & Answers

• Question 541:

  Which of the following symptoms can occur frequently in infants suffering from mediumchain acyl- CoA dehydrogenase (MCAD) deficiency if periods between meals are protracted?

  A. bone and joint pain and thrombocytopenia

  B. hyperammonemia with decreased ketones

  C. hyperuricemia and darkening of the urine

  D. hypoglycemia and metabolic acidosis with normal levels of ketones

  E. metabolic alkalosis with decreased bicarbonate

  Correct Answer: D

  Section: Biochemistry In infants, the supply of glycogen lasts less than 6 hours and gluconeogenesis is not sufficient to maintain adequate blood glucose levels. Normally, during periods of fasting (in particular during the night) the oxidation of fatty acids provides the necessary ATP to fuel hepatic gluconeogenesis as well as ketone bodies for nonhepatic tissue energy production. In patients with MCAD deficiency there is a drastically reduced capacity to oxidize fatty acids. This leads to an increase in glucose usage with concomitant hypoglycemia. The deficit in the energy production from fatty acid oxidation, necessary for the liver to use other carbon sources, such as glycerol and amino acids, for gluconeogenesis further exacerbates the hypoglycemia. Normally, hypoglycemia is accompanied by an increase in ketone formation from the increased oxidation of fatty acids. In MCAD deficiency there is a reduced level of fatty acid oxidation, hence near normal levels of ketones are detected in the serum. None of the other choices (A, B, C, and E) reflect symptoms related in any way to MCAD deficiency and are not in themselves indicative of any specific disorder per se.

• Question 542:

  In an assay for the presence of a specific disease gene alelle in several individuals, you isolate genomic DNA from each and perfom polymerase chain reaction (PCR) using gene-specific primers. The PCR product is expected to have a recognition site for the restriction endonuclease BamHI. Following PCR and BamHI digestion, the products are separated by gel electrophoresis and the results are shown in below figure. Which lane corresponds to the individual demonstrating heterozygosity for the BamHI site?

  

  A. 1

  B. 2

  C. 3

  D. 4

  E. 5

  Correct Answer: B

  Section: Biochemistry Someone who exhibits heterozygosity would harbor two distinct alelles. In the case of this analysis, they would be identified as containing a copy of the gene that does not harbor the BamHI site and a copy that does harbor the site. The presence of the BamHI site in the PCR product in this example would result in the generation of 300 and 100 bp fragments. The lack of the site would yield a product of 400 bp. Thus, following PCR amplification and BamHI digestion of DNA from a heterozygote, one would be able to observe three bands of equal intensity. A person who was homozygous for having the BamHI-containing sequence would result in two bands (choice A) whose intensities would be greater than the three of the heterozygote. A person homozygous for the lack of the BamHI site would yield a single 400 bp band (choice D). The banding patterns observed in lanes 3 (choice C) and 5 (choice E) would not be possible from this analysis.

• Question 543:

  The ability of rod cells in the eye to respond to light and transmit that response to the optic nerve requires that the 11-cis form of vitamin A be attached to which of the following proteins?

  A. cGMP phosphodiesterase

  B. Na+ channel

  C. rhodopsin

  D. scotopsin

  E. transducin

  Correct Answer: D

  Section: Biochemistry Both rod and cone cells contain a photoreceptor pigment in their membranes. The photosensitive compound (photoreceptor) of most mammalian eyes is a complex of protein and an aldehyde form of vitamin A. The protein component is a member of the opsin family called scotopsin. The photoreceptor of rod cells is specifically called rhodopsin (choice C) or visual purple, which is a complex between the protein scotopsin and the 11-cis-retinal form of vitamin A. Intracellularly, rhodopsin is coupled to a specific G- protein called transducin (choice E). When the rhodopsin is exposed to light it is bleached releasing the 11- cis-retinal from opsin. Absorption of photons by 11-cis-retinal triggers a series of conformational changes on the way to conversion all-trans-retinal. The release of opsin results in a conformational change in the photoreceptor. This conformational change activates transducin, leading to an increased GTP-binding by the alpha-subunit of transducin. Binding of GTP releases the alpha- subunit from the inhibitory beta- and gamma-subunits. The GTPactivated alpha-subunit in turn activates an associated phosphodiesterase (choice A), an enzyme that hydrolyzes cyclic-GMP (cGMP) to GMP. Cyclic GMP is required to maintain the Na+ channels (choice B) of the rod cell in the open conformation. The drop in cGMP concentration results in complete closure of the Na+ channels.

• Question 544:

  Patients with poorly controlled diabetes mellitus have elevated levels of blood glucose. One severe consequence of the hyperglycemia is an increase in glucose attachment to serum proteins. Which of the following proteins, when glycosylated, is an excellent measure of the length of time someone has suffered from an episode of hyperglycemia?

  A. albumin

  B. cholesterol

  C. fatty acids

  D. hemoglobin

  E. transferrin

  Correct Answer: D

• Question 545:

  During the process of protein synthesis, the factor eEF-2 induces the hydrolysis of GTP. The energy of this hydrolysis is coupled to which of the following?

  A. amino acid activation by attachment to a tRNA

  B. correct alignment of the mRNA on the 40S ribosome

  C. formation of the 80S initiation complex

  D. formation of the peptide bond

  E. translocation of the ribosome

  Correct Answer: E

  Section: Biochemistry The translation factor, eEF-2, is involved in the process of peptide elongation. Specifically, eEF-2 catalyzes the GTP-dependent translocation of the ribosomes along the mRNA to the next codon. Attachment of an amino acid to a tRNA (choice A) is catalyzed by the family of aminoacyl-tRNA synthetases. Alignment of the mRNA on the 40S ribosome (choice B) is facilitated by the initiation factor eIF-1. Formation of the 80S initiation complex (choice C) occurs after complete assembly of the 40S preinitiation complex and requires the activity of eIF-5. Formation of the peptide bond (choice D) occurs through the action of peptidyltransferase.

• Question 546:

  The metabolic pathway depicted in below figure is critically important as a means of energy production in skeletal muscle cells. Which of the following correctly identifies this pathway?

  

  A. ADA cycle

  B. hypoxanthine-guanine phosphoribosyltransferase (HGPRT) cycle

  C. nonoxidative cycle in pentose phosphate pathway

  D. purine nucleotide cycle

  E. urea cycle

  Correct Answer: D

  Section: Biochemistry The synthesis of AMP from IMP and the salvage of IMP via AMP catabolism have the net effect of deaminating aspartate to fumarate. This process has been termed the purine nucleotide cycle. This cycle is very important in muscle cells. Increases in muscle activity create a demand for an increase in the TCA cycle, to generate more NADH for the production of ATP. However, muscle lacks most of the enzymes of the major anapleurotic reactions. Muscle replenishes TCA cycle intermediates in the form of fumarate generated by the purine nucleotide cycle. There is no HGPRT or ADA cycle and hence, choices Aand B do not represent valid options. Choices C and E constitute pathways that do not involve nucleotides.

• Question 547:

  Endothelial cells respond to certain stimuli by inducing the conversion of arginine to citrulline leading to the activation of a signaling cascade that involves which of the following?

  A. adenylate cyclase

  B. guanylate cyclase

  C. phosphatidylinositol-3-phosphate kinase (PI3K)

  D. PLC-gamma

  E. protein kinase C (PKC)

  Correct Answer: B

  Section: Biochemistry Certain endothelial cell-stimulating signals, such as vasodilators, induce the production of NO during the conversion of arginine to citrulline via a reaction catalyzed by nitric oxide synthase (NOS). When NO is produced, it passes out of the endothelial cells and enters the underlying smooth muscle cells. Within smooth muscle cells, NO reacts with the heme moiety of a soluble guanylyl cyclase, resulting in activation of the latter and a consequent elevation of intracellular levels of cGMP. The net effect is the activation of cGMP-responsive enzymes, which lead to smooth muscle cell relaxation. None of the signaling enzymes or molecules (choices A, CE) are involved in the NO-mediated signaling cascade.

• Question 548:

  The ability of the liver to regulate the level of blood glucose is critical for survival. Anumber of sources of carbon atoms of nonhepatic origin are used by the liver for gluconeogenesis. However, the net conversion of carbons from fat into carbons of glucose cannot occur in humans because of which of the following?

  A. Fat oxidation occurs in the mitochondria and gluconeogenesis occurs in the cytosol.

  B. States of catabolism and anabolism are never concurrently active.

  C. Storage of fats occurs in adipose tissue and gluconeogenesis occurs in liver and kidney.

  D. The carbons of acetyl-CoA from fat oxidation are lost as C in the TCA cycle.

  E. The carbons of acetyl-CoA from fat oxidation inhibit conversion of pyruvate to oxaloacetate.

  Correct Answer: D

  Section: Biochemistry When the carbons of fatty acids are oxidized for energy production, the by-product of that process is the two-carbon compound, acetyl-CoA. Acetyl-CoA can then enter the TCA cycle for complete oxidation. Although, several compounds of the TCA cycle can be directed into the gluconeogenic pathway of glucose synthesis, the carbons of acetyl-CoA cannot provide a net source of carbon in that latter pathway. This is due to the fact that, following entry of the two carbons of acetyl-CoA into the TCA cycle, two carbons are lost as CO2 during the subsequent reactions of the cycle. The subcellular compartmentalization of fat oxidation and gluconeogenesis (choice A) has no bearing on net carbon deposition into glucose. Anabolic and catabolic reactions (choice B) are always occuring concurrently in cells but at different rates dependent on cellular status. The site of fat storage (choice C) has no bearing on net incorporation of carbon into glucose. Acetyl-CoA does not inhibit conversion of pyruvate to oxaloacetate (choice E) but acts as an allosteric activator of pyruvate carboxylase, a gluconeogenic enzyme.

• Question 549:

  The parents of a 1-year-old boy are alarmed at the increasing frequency of their child biting his lips and finger tips. In addition, on several occasions they have noticed what appear to be particles of "orange sand" in their son's diapers. They report to their pediatrician that they believe their child is delayed in acquiring motor skills such as holding up his head and sitting unaided. Clinical tests performed on serum and urine indicate a threefold increase in serum uric acid and a tenfold elevation in the urinary ratio of uric acid to creatinine. These findings are suggestive of which of the following disorders?

  A. adenosine deaminase deficiency

  B. adenylosuccinate lyase deficiency

  C. Lesch-Nyhan disease

  D. purine nucleotide phosphorylase deficiency

  E. orotic aciduria

  Correct Answer: C

  Section: Biochemistry Deficiencies in the purine nucleotide salvage enzyme, HGPRT, cause three overlapping clinical syndromes. The most severe deficiency (patients having less than 1.5% residual enzyme activity) results in debilitating neurologic disability, overproduciton of uric acid, and behavioral abnormalities that include impulsive and self-injurious activities such as biting finger tips and lips. This severe form of HGPRT deficiency is referred to as Lesch-Nyhan disease. The overproduction of uric acid leads to symptoms of gout and the appearance of "orange sand" in the urine. Deficiencies in ADA (choice A), another purine nucleotide salvage enzyme, are the cause of severe-combined immunodeficiency syndrome, SCID. SCID is characterized by a lack of both cell-mediated and humoral immunity. ADSL (choice B) is an enzyme in the pathway of de novo purine nucleotide synthesis. It is also an important component of the purine nucleotide cycle (see below figure). Deficiencies in ADSLcause psychomotor retardation, epileptic seizures, growth retardation, and muscle wasting. Deficiencies in PNP (choice D) result in a form of immunodeficiency characterized by defective cell-mediated responses. Afflicted individuals may also have normal, hyperactive, or reduced humoral immunity. Orotic aciduria is caused by deficiencies in the de novo pathway of pyrimidine nucleotide synthesis. Adeficiency in either of the last two enzymes in the pathway, orotate phosphoribosyltransferase or OMP decarboxylase, leads to orotic aciduria.

• Question 550:

  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?

  A. Fabry disease

  B. Gaucher disease

  C. Krabbe disease

  D. Niemann-Pick disease type II C

  E. Tay-Sachs disease

  Correct Answer: B

  Section: Biochemistry 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 alphagalactosidase 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.