USMLE USMLE Certifications USMLE-STEP-1 Questions & Answers

• Question 501:

  Resistance to Type I diabetes has been shown to be associated with a specific polymorphic allele. Which of the following loci represents this allele?

  A. a VNTR in the 5' region of the insulin gene

  B. glutamic acid decarboxylase (GAD)

  C. HLA-B27

  D. HLA-DQ

  E. HLA-DR3

  Correct Answer: D

  Section: Biochemistry Class I and class II genes of the major histocompatibility locus (MHC), which comprise the HLA genes, are highly polymorphic and express hundreds of different alleles in humans. Many of these polymorphic loci are associated, either positively or negatively, with autoimmune-related disorders. Inheritance of the class II HLA-DQ allele has been highly correlated to resistance to development of Type I diabetes. Conversely, the DR3 allele (choice E) is positively correlated with development of Type I diabetes. Autoantibodies to GAD (choice B) are found in over 80% of patients with Type I diabetes. Different VNTR structure present in the promoter region of the insulin gene (choice A) has been shown to indicate susceptibility to Type I diabetes. The HLA-B27 allele (choice C) is correlated with ankylosing spondylitis.

• Question 502:

  Vitamin K serves as a coenzyme in reactions that result in the modified activity of several enzymes of the blood coagulation cascade. Which of the following amino acid modifications requires the activity of vitamin K?

  A. aspartate to beta-carboxyaspartate

  B. glutamate to gamma-carboxyglutamate

  C. lysine to hydroxylysine

  D. lysine to beta-methyllysine

  E. proline to hydroxyproline

  Correct Answer: B

  Section: Biochemistry factors II, VII, IX, X, and protein C) bind calcium and are thus activated following cleavage of their zymogen forms. The ability of these proteins to bind calcium requires posttranslationally modified glutamate residues. The modification is a gamma-carboxylation yielding gamma-carboxyglutamate (gla) residue. The carboxylation reaction has an absolute requirement for vitamin K as a cofactor. None of the other amino acid modifications (choices A, C, D, and E) require vitamin K as a cofactor. Hydroxylation of proline (choice E) and lysine (choice C) is carried out by enzymes that require vitamin C as a cofactor.

• Question 503:

  Steroid hormones interact with specific receptors within target cells. The steroid-receptor complexes then regulate the rate of which of the following intracellular processes?

  A. posttranscriptional processing of specific mRNAs

  B. posttranslational processing of specific proteins

  C. replication of DNA

  D. transcription of specific genes

  E. translation of specific mRNAs

  Correct Answer: D

  Section: Biochemistry Steroid hormones are lipophilic and hence freely penetrate the plasma membrane of all cells. Within target cells, steroid hormones interact with specific receptors. These receptor proteins are composed of two domains: a hormone-binding domain and a DNA-binding domain. Following hormone-receptor, interaction the complex is activated and enters the nucleus. The DNA-binding domain of the receptor interacts with specific nucleotide sequences termed hormone response elements (HREs). The binding of steroid-receptor complexes to HREs results in an altered rate of transcription of the associated gene(s). The effects of steroid-receptor complexes on specific target genes can be either stimulatory or inhibitory with respect to the rate of transcription. Complexes of steroid with receptor have no direct effect on posttranscriptional processing of RNA (choice A), posttranslational events (choice B), DNA replication (choice C), or translation (choice E).

• Question 504:

  PDH is a complex multisubunit enzyme. Which of the following exerts a positive influence on the activity of PDH?

  A. acetyl-CoA

  B. ATP

  C. dephosphorylation

  D. NADH

  E. phosphorylation

  Correct Answer: C

  Section: Biochemistry Regulation of the PDH complex is effected by both allosteric means and by phosphorylation (see below figure). Allosteric effectors of the enzyme complex are of both positive and negative type. The complex is phosphorylated by a specific kinase identified as PDH kinase and phosphate is removed by PDH phosphatase. When in the unphosphorylated state the complex is much more active, therefore the activity of PDH phosphatase is important for maintaining the PDH complex in the active state. Acetyl- CoA (choice A) and NADH (choice D) are both allosteric inhibitors of the nonphosphorylated form of the PDH complex and also serves to activate PDH kinase leading to phosphorylated and inhibited PDH. Like acetyl- CoA and NADH, ATP (choice B) allosterically activates the PDH kinase leading to phosphorylated and inhbited PDH. Phosphorylation (choice E) inhibits the activity of the PDH complex.

• Question 505:

  The incretins are hormones that are released in response to the consumption of food. Which of the following represents one of the major effects of incretin release from intestinal epithelial cells?

  A. activation of gastric emptying ensuring release of ingested food

  B. enhancement in adipocyte triacylglycerol synthesis

  C. enhancement of insulin secretion from the pancreas

  D. repression of pancreatic cell proliferation

  E. stimulation of gastric acid secretion to aid in digestion

  Correct Answer: C

  Section: Biochemistry The incretins are molecules associated with food intake-stimulation of insulin secretion from the pancreas. Two of the many GI hormones have significant effects on insulin secretion and glucose regulation. These hormones are GLP-1 and glucose-dependent insulinotropic peptide (GIP). Both of these gut hormones represent the incretins. In contrast to activation of gastric emptying (choice A) and repression of pancreatic cell proliferation (choice D), GLP-1 inhibits gastric emptying and promotes a sense of satiety, induces proliferation, and represses apoptosis of pancreatic beta-cells. The incretins do not enhance adipose triacylglycerol synthesis (choice B). Repression of gastric acid secretion, not sitmulation (choice E) is one of the additional functions of GIP.

• Question 506:

  Achild born and raised in Chicago planned to spend the summer on a relative's fruit farm and help with the harvest. The summer passed uneventfully, but several days after the harvest began the child became jaundiced and very sick. On admission to the hospital the following clinical findings were recorded: in addition to the expected hyperbilirubinemia, the patient was hypoglycemic, had a markedly elevated rise in blood fructose concentration, and was hyperlactic acidemic. Further history taking revealed that during the harvest it was customary for the family to indulge in fruit-filled meals and to snack freely on fruit while carrying out the harvest. The following conclusions were reached. The elevated blood fructose was due to which of the following?

  A. an allergic reaction to constituents in the fruit diet

  B. defective hepatic fructokinase

  C. defective hepatic glucokinase

  D. defective hepatic fructose-1-phosphate aldolase (aldolase B)

  E. defective hepatic fructose-1,6-bisphosphate aldolase (aldolase A)

  Correct Answer: D

  Section: Biochemistry Patients with hereditary fructose intolerance have defective function in hepatic fructose-1-phosphate aldolase (also called aldolase B). This enzyme hydrolyzes fructose-1-phosphate to glyceraldehyde and dihydroxyacetone phosphate. The reaction is the second in the hepatic pathway of fructose metabolism, the initial one being the phosphorylation of fructose at the 1 position by fructokinase (choice B). When fructose is high in the diet (as in the consumption of large quantities of fruit) the capability to divert the fructose into the glycolytic pathway is severely impaired. Fructose becomes trapped in the liver as fructose- 1-phosphate. Due to the lack of aldolase B, the capacity to phosphorylate fructose becomes limiting due to feedback inhibition of fructokinase, resulting in an elevation in serum fructose levels. Hepatic glucokinase (choice C) and aldolase A (choice E) are not involved in the metabolism of fructose. An allergic reaction (choice A) would not manifest with elevated serum fructose, hyperbilirubinemia, or hyperlacticacidemia.

• Question 507:

  The phosphorylase kinase-associated regulatory protein identified by the letter A in below figure is a calcium-binding protein. Which of the following proteins represents this regulatory subunit?

  

  A. calmodulin

  B. fructose-2,6-bisphosphate

  C. glycogen synthase kinase-3

  D. phosphoprotein phosphatase

  E. phosphoprotein phosphatase inhibitor-1

  Correct Answer: A

• Question 508:

  Mosaicism refers to a condition in which an individual has two or more genetically distinct cell types, derived from a single zygote, but that differ because of mutation or chromosomal aberration. Mosaicism occurs with a frequency of approximately 30% in females who are phenotypically normal but harbor gonadal dysgenesis, sexual immaturity, and infertility. These affected females also are short in stature, have webbing of the neck, and swelling of the hands and feet, as well as cardivascular and renal abnormalities. These symptoms are associated with which of the following diseases?

  A. achondroplasia

  B. Duchenne muscular dystrophy

  C. fragile X syndrome

  D. Kleinfelter syndrome

  E. Turner syndrome

  Correct Answer: E

  Section: Biochemistry Turner syndrome is characterized by phenotypically normal females who are sexually immature and have gonadal dysgenesis and a host of somatic abnormalities. These symptoms arise due to chromosomal abnormalities in one of the X chromosome as well as due to monosomy for the X chromosome. Only around 5% of monosomy X fetuses survive to birth. Some 15% of Turner syndrome females are mosaic for the karyotype 45,X:46,XX and another 15% are mosaic for a 45,X cell line plus a 46,X, abnormal X cell line or a 47,XXX cell line. Achondroplasia (choice A) is the single most common form of dwarfism, which results from two specific defects in the gene encoding fibroblast growth factor receptor 3 (FGFR3). Symptoms of achondroplasia include rhizomelic short stature, midface hypoplasia, short ribs, and trident hand. DMD (choice B) is an X-linked condition whose symptoms occur in affected males in early childhood and only very rarely affects females. DMD is caused by defects in the dystrophin protein, which is involved in the contractile apparatus of muscle cells. Fragile X syndrome (choice C) is the most common form of inherited mental retardation. The symptoms result from the loss of a portion of the X chromosome due to a site of fragility caused by the amplification of a trinucleotide repeat sequence in the FMR1 gene. Symptoms of fragile X are most severe in males (affected females have much milder symptoms) and include severe mental retardation and facial abnormalities such as prominent jaw, forehead, and ears. Kleinfelter syndrome (choice D) is associated with males harboring two or more X chromosomes (e.g., 47,XXY). Symptoms appear in puberty and affected individuals have a greater than expected frequency of social pathology. Although significant mental retardation is not associated with most Kleinfelter patients, the more X chromosomes and individual harbors the higher likelihood of mental retardation.

• Question 509:

  Acromegaly is characterized by protruding jaw, enlargement of the nose, hands, feet, and skull, and a thickening of the skin. This disorder is the result of excessive production of which of the following hormones?

  A. corticotropin-releasing hormone

  B. GnRH

  C. growth hormone

  D. insulin-like growth factor-II (IGF-II) E. thyroid-stimulating hormone

  Correct Answer: C

  Section: Biochemistry Acromegaly results when there is an excess production of growth hormone after epiphysial closure and cessation of long bone growth. Excessive production of corticotropin-releasing hormone (choice A) would result in an increase in ACTH production, which would lead to enhanced glucocorticoid and mineralocorticoid production. Excessive production of GnRH (choice B) would lead to increased production of LH, FSH, and hCG, with consequent effects on the female reproductive system. Excessive production of IGF-II (choice D) could lead to abnormal neonatal development since it is expressed only during this period. Excessive production of thyroid-stimulating hormone (choice E) would lead to increased release of the thyroid hormones, leading to multisystemic involvement such as rapid heart rate, nervousness, inability to sleep, weight loss, excessive sweating, and sensitivity to heat.

• Question 510:

  Under conditions of anaerobic glycolysis, the NAD+ required by glyceraldehyde-3-phosphate dehydrogenase is supplied by a reaction catalyzed by which of the following enzymes?

  A. glycerol-3-phosphate dehydrogenase

  B. alpha-ketoglutarate dehydrogenase

  C. lactate dehydrogenase

  D. malate dehydrogenase

  E. PDH

  Correct Answer: C