Workbook of Biochem
Workbook of Biochem
Workbook of Biochem
Biochemistry
How to Use the Workbook with the Videos
Using this table as a guide, read the Facts in First Aid for the USMLE Step 1 2016,
watch the corresponding First Aid Express 2016 videos, and then answer the workbook
questions.
Questions
MOLECULAR
1. Which histone is not part of the nucleosome core? (p 48) ________________________________
2. What is DNA called when it is condensed and transcriptionally inactive? (p 48) _______________
4. What effect does greater G-C content have on the melting temperature of DNA? (p 49)
______________________________________________________________________________
7. A 12-year-old boy with moderate intellectual disability visits his physician because of painful
swollen joints. During the examination, the boy makes several uncontrolled spastic muscle
movements. His medical history includes muscular hypotonia diagnosed when he was 5 months
old. When he was 3 years old he was referred to a pediatric dentist for severe repetitive biting of
his lip and tongue. What is the most likely diagnosis? (p 50) ______________________________
______________________________________________________________________________
______________________________________________________________________________
______________________________________________________________________________
8. What enzyme “proofreads” DNA synthesis with its exonuclease activity in prokaryotic DNA replica-
tion? In which direction can it remove nucleotides? (p 51) ________________________________
9. What enzyme degrades the RNA primer and replaces it with DNA during prokaryotic DNA
replication? (p 51) _______________________________________________________________
11. Silent mutations often result from changes in which position of a codon? (p 52) _______________
12. What kind of mutation denotes a DNA change that results in the misreading of all nucleotides
downstream from it? (p 52) ________________________________________________________
13. What specific DNA repair mechanism is defective in xeroderma pigmentosum? (p 53) _________
______________________________________________________________________________
14. In single-stranded DNA repair, how are nucleotide-excision and base-excision repair different? (p
53) ___________________________________________________________________________
15. Hereditary nonpolyposis colorectal cancer results from the loss of which DNA repair mechanism?
(p 53) _________________________________________________________________________
16. What commonly results from a mutation within a promoter? (p 54) _________________________
17. What type of RNA is the largest? The smallest? The most numerous? (p 54) ________________
______________________________________________________________________________
18. What poisonous protein that inhibits RNA polymerase II is found in death cap mushrooms? (p 54)
______________________________________________________________________________
21. Patients with which disease make antibodies to spliceosomal small nuclear ribonucleoproteins? (p
55)_________________________________________________________________________
22. β-Thalassemia can be caused by a mutation causing splicing defects in a process that combines
different exons within a single gene. What mechanism allows the same gene to encode for various
different proteins? (p 55) __________________________________________________________
23. Which molecule in the process of gene expression into proteins is inhibited by microRNAs (DNA,
RNA polymerase, mRNA, ribosome, or final protein)? (p 55)______________________________
24. Explain the three steps of the elongation phase of protein synthesis. (p 57) __________________
______________________________________________________________________________
______________________________________________________________________________
25. What is the category of proteins like Hsp60 which help other proteins fold properly after translation?
(p 57) _________________________________________________________________________
CELLULAR
26. Fill in the boxes on the following diagram, noting the phases of the mitotic cell cycle. (p 58)
27. Which transition in the cell cycle is prevented by Rb and p53 tumor suppressors? (p 58) ________
______________________________________________________________________________
29. Name two cells that are rich in rough endoplasmic reticulum. (p 58) ________________________
30. Name two cells that are rich in smooth endoplasmic reticulum. (p 58) _______________________
31. A child presents with coarse facial features, clouded corneas, restricted joint movement, and high
plasma levels of lysosomal enzymes. What is the most likely diagnosis? (p 59) ________________
32. Which molecular motor protein is used for anterograde transport along microtubules? (p 60) _____
______________________________________________________________________________
35. A 22-year-old woman presents with a history of recurrent pneumonia. X-ray of the chest shows
dextrocardia. What is the most likely diagnosis? (p 60) __________________________________
36. Cilia, flagella, mitotic spindles, neurons, and centrioles are composed of which cytoskeletal
element? (p 60) _________________________________________________________________
37. Vimentin, desmin, cytokeratin, glial fibrillary acid proteins, and neurofilaments are examples of
which type of cytoskeletal element? (p 60) ____________________________________________
38. What effect does digoxin’s inhibition of Na+-K+ ATPase have on cardiac contractility? (p 61) _____
______________________________________________________________________________
41. What disease leads to an inability to form procollagen from pro α chains? (p 62) ______________
______________________________________________________________________________
42. A baby is born with multiple fractures and hearing loss. What finding would most likely be seen
during the ophthalmologic examination? (p 62) ________________________________________
43. A patient presents with hyperextensible skin, easy bruising, and hypermobile joints. What is the
most likely diagnosis? (p 63) _______________________________________________________
44. Which enzyme involved in collagen synthesis will have decreased activity in a patient who has a
mutation that impairs copper absorption and transport? (p 63) _____________________________
46. Which lung disorder can result from excess elastase activity? (p 64) ________________________
LABORATORY TECHNIQUES
47. Describe each of the following blot techniques: Southern, Northern, and Western (p 65)
Southern blot: ___________________________________________________________________
_______________________________________________________________________________
_______________________________________________________________________________
_______________________________________________________________________________
48. Which assay can quantify the fraction of cells in a liquid sample that express a specific set
of surface markers? (p 66) _________________________________________________________
49. Which assay can measure the expression level of many genes simultaneously? (p 66) __________
_______________________________________________________________________________
50. What is the advantage of a Western blot over an ELISA? (p 67) ____________________________
_______________________________________________________________________________
51. What is the advantage of fluorescence in situ hybridization over karyotyping? (p 67) ___________
______________________________________________________________________________
52. What is the most direct lab technique for detecting autosomal trisomies? (p 67) _______________
______________________________________________________________________________
GENETICS
53. Explain loss of heterozygosity. (p 68) ________________________________________________
______________________________________________________________________________
54. A genetic disease that shows _______________________________ may have mutations at one of
several different loci that produce the same phenotype. (p 68)
55. In terms of p and q, what is the heterozygote prevalence in a population that is in Hardy-Weinberg
equilibrium? (p 69) _______________________________________________________________
56. How is Prader-Willi syndrome inherited? What are the symptoms? (p 69) ____________________
______________________________________________________________________________
57. How is Angelman syndrome inherited? What are the symptoms? (p 69) _____________________
______________________________________________________________________________
58. Which mode of inheritance is represented by each of the following pedigrees? (p 70)
_____ D. _____ E.
1. Autosomal dominant
2. Autosomal recessive
3. Mitochondrial inheritance
4. X-linked dominant
5. X-linked recessive
59. What percentage of sons of a carrier mother is expected to inherit an X-linked recessive disease?
(p 70) _________________________________________________________________________
60. True or False: A mother with an X-linked dominant disease may pass the disease to her sons but
not to her daughters. (p 70) ________________________________________________________
62. A patient has multiple telangiectasias and skin discolorations, and notes recurrent epistaxis. What
vascular pathology would you expect to find? (p 71) _____________________________________
______________________________________________________________________________
64. A tall man comes to the emergency room with the combination of a dissecting ascending aorta and
acute mitral valve prolapsed. What disorder best explains these findings? (p 71) _____________
______________________________________________________________________________
65. You notice café-au-lait spots and cutaneous neurofibromas all over a patient’s skin. On which
chromosome is the gene that causes this disorder? (p 71) _______________________________
66. Cystic fibrosis results from a defect in which gene? Which chromosome? Which ion channel? (p
72) _________________________________________________________________________
67. Which drug can be used to loosen mucus plugs in patients with cystic fibrosis? (p 72) __________
68. A patient with cystic fibrosis has an increased risk a deficiency of which vitamins? (p 72)
______________________________________________________________________________
69. A 4-year-old boy needs to use his upper extremities to push against his legs in order to stand up.
What maneuver is he using? (p 73) _________________________________________________
70. A male patient has a long face, a large jaw, large ears, autism, and macroorchidism. What is the
most likely diagnosis? (p 73) _______________________________________________________
71. Before his anticipated death, a 42-year-old man had received many years of treatment for
depression, severe cognitive decline, and involuntary writhing movements. His father had similar
symptoms shortly before his death. What is the cause of this patient’s most likely disease? (pp 71
and 73)________________________________________________________________________
______________________________________________________________________________
72. A newborn is diagnosed with Down syndrome. She is vomiting bilious material. What is the most
likely cause? (p 74) ______________________________________________________________
73. The BRCA1 and BRCA2 genes are on which chromosome(s)? (p 75)_______________________
NUTRITION
74. Match each set of symptoms/conditions with the vitamin that is deficient. (pp 77-81)
_____ A. Bruising, anemia, swollen gums, and poor wound healing 1. Biotin
_____ B. Cheilosis and corneal vascularization 2. Folic acid
_____ C. Convulsions, hyperirritability, peripheral neuropathy, 3. Vitamin A
and sideroblastic anemia 4. Vitamin B1
_____ D. Dermatitis, enteritis, and alopecia 5. Vitamin B2
_____ E. Dermatitis, enteritis, alopecia, and adrenal insufficiency 6. Vitamin B3
_____ F. Diarrhea, dermatitis, and dementia 7. Vitamin B5
_____ G. Hemolytic anemia, muscle weakness, and neuropathy 8. Vitamin B6
_____ H. Hemorrhagic disease of the newborn 9. Vitamin B12
_____ I. Hypocalcemic tetany 10. Vitamin C
_____ J. Macrocytic, megaloblastic anemia with no 11. Vitamin D
neurologic problems 12. Vitamin E
_____ K. Macrocytic, megaloblastic anemia, subacute combined 13. Vitamin K
degeneration, paresthesia, and optic neuropathy
_____ L. Night blindness
_____ M. Wernicke-Korsakoff syndrome
75. Which vitamin or mineral is a cofactor for many transcription factors, and has dysgeusia as a
symptom of its deficiency? (p 82) ___________________________________________________
76. Does ethanol metabolism by hepatocytes produce or consume NADH? (p 83) ________________
______________________________________________________________________________
METABOLISM
77. Match each of the following processes with its rate-determining enzyme. (p 84)
78. In the following diagram, fill in the rectangles with the intermediates and products. Which steps of
glycolysis are reversible? (Add one- or two- sided arrows to the squares.) (p 85)
Glucose
Fructose-6-P
Citrate
Isocitrate
Glyceraldehyde-3-P Fumarate
Succinate
3-phosphoglycerate
2-phosphoglycerate
Pyruvate
PDH
79. How many ATP molecules can be created by the aerobic and anaerobic metabolism of glucose? (p
86) ________________________________________________________________________
______________________________________________________________________________
80. The α-ketoglutarate dehydrogenase complex and the pyruvate dehydrogenase complex require the
same five cofactors; what are these cofactors? (p 87) __________________________________
_______________________________________________________________________________
82. What are Heinz bodies? What are bite cells? (p 90) _____________________________________
______________________________________________________________________________
______________________________________________________________________________
83. Fill in the boxes on the image below, noting the substrates of the urea cycle. (p 93)
84. A two-day-old male infant is irritable and lethargic. Serum studies show increased orotic acid and
hyperammonemia, with a normal hematocrit and MCV. What is the most likely diagnosis? (p 94)
__________________________________________________
85. Fill in the boxes in the following chart, noting the enzymes that catalyze each step of catecholamine
synthesis. (p 94)
86. A 16-year-old boy presents for a routine visit. Physical examination shows symptoms consistent
with Fabry disease. What is the inheritance pattern of this disease? (p 100) _________________
______________________________________________________________________________
87.Using the list in the box, name the deficient enzyme and accumulated substrate(s) for each lysosomal
storage disease listed in the chart below. (Some answers may be used more than once)
(p 100)
α-galactosidase A
Hexosaminidase A
Sphingomyelinase
α-L-iduronidase
GM ganglioside
2
β-glucocerebrosiderase
Cerebroside sulfate
Galactocerebrosidase
Galactocerebroside
Sphingomyelin
Arylsulfatase A
Glucocerebroside
Ceramide trihexoside
Heparan sulfate / dermatan sulfate
Iduronate sulfatase
Accumulated
Disease Deficient Enzyme
Substrate
Fabry disease
Gaucher disease
Hunter syndrome
Hurler syndrome
Krabbe disease
Metachromatic
leukodystrophy
Niemann-Pick disease
Tay-Sachs disease
90. Which cell type(s) cannot use ketones as an energy source? Why? (p 103) __________________
_______________________________________________________________________________
91. What is the target enzyme of the drug lovastatin? (p 103) ________________________________
92. Which apolipoprotein binds to the LDL receptor? On which lipoproteins is it found? (p 104) _____
______________________________________________________________________________
Answers
MOLECULAR
1. H1.
2. Heterochromatin.
5. Ribonucleotide reductase.
7. This child has Lesch-Nyhan syndrome, which is characterized by intellectual disability, self-
mutilation, aggression, hyperuricemia, gout, and choreoathetosis. It is caused by the absence of
HGPRT, which leads to a defective purine salvage pathway.
8. DNA polymerase III has 3' to 5' exonuclease activity for proofreading.
9. DNA polymerase I.
12. Frameshift.
14. During nucleotide repair, the entire nucleotide structure is removed and replaced. During base
excision repair, the base is clipped off of the sugar and repaired without the entire backbone of the
DNA being taken apart.
17. mRNA is the largest type, tRNA is the smallest, and rRNA is the most numerous type of RNA.
21. Lupus.
22. Alternative splicing. (In this case, the alternative splicing yields a pathologic protein.)
24. (1) Aminoacyl-tRNA binds to the A site. (2) Peptidyltransferase adds a peptide to the amino acid
chain at site A. (3) The ribosome advances three nucleotides in the 3′ direction, thereby moving the
peptidyl tRNA to the P site.
CELLULAR
26.
27. Transition from G1 to S phase. (Defective cells are not allowed to undergo DNA synthesis.)
29. Goblet cells (secrete mucus) and plasma cells (secrete antibodies).
32. Kinesin.
33. Griseofulvin.
34. Mebendazole..
36. Microtubules.
40. Scurvy; the limes supplied the sailors with the vitamin C they needed during their long voyage (and
earned them the nickname "limeys").
45. Fibrillin.
46. Emphysema. (α1-Antitrypsin inhibits elastase, which degrades elastin; therefore, lack of α1-
antitrypsin can lead to loss of elastin in the lungs, thereby resulting in emphysema.)
LABORATORY TECHNIQUES
47. Southern: DNA is run on an electrophoresis gel and transferred to a filter; the DNA on the filter is
denatured and exposed to a labeled DNA probe; the double-stranded DNA is visualized when the
filter is exposed to film.
Northern: RNA is run on an electrophoresis gel and transferred to a filter; the RNA on the filter is
exposed to a labeled DNA probe; the hybrid DNA-RNA molecule is visualized when the filter is
exposed to film.
Western: Sample protein is separated via gel electrophoresis and transferred to a filter; labeled
antibody is used to bind and detect the protein of interest.
49. Microarrays.
50. A Western blot has greater specificity than an ELISA because it also detects the size of the target
being identified.
51. FISH allows for identification of anomalies at the molecular level, including deletions that are too
small to see on a karyotype.
52. Karyotyping.
GENETICS
53. When a tumor suppressor gene has only one functional allele due to an inherited mutation or
deletion of the other, and then a cell loses the remaining allele as well. Consequently, having no
functional alleles permits a neoplastic transformation.
55. 2pq.
56. Prader-Willi syndrome is inherited via deactivation of the paternal copies of genes on chromosome
15 or can occur via uniparental disomy. Symptoms include mental retardation, hyperphagia,
obesity, hypogonadism, and hypotonia.
57. Angelman syndrome is inherited via deactivation of the maternal copies of genes on chromosome
15 or can occur via uniparental disomy. Symptoms include mental retardation, seizures, ataxia, and
inappropriate laughter.
59. 50%.
64. Marfan syndrome. (It is associated with cystic medial necrosis of the aorta [which may lead to a
dissection] as well as a floppy mitral valve prone to prolapse.)
66. CF is due to a defect in the CFTR gene on chromosome 7 that affects the chloride channel.
67. N-acetylcysteine.
69. Gower maneuver. (This action is necessary due to weakness of the proximal muscles.)
70. Fragile X syndrome. (Remember: Fragile X = eXtra large testes, jaw, and ears.)
71. The patient has classic symptoms of Huntington disease, which is caused by an expansion of CAG
trinucleotide repeats on chromosome 4.
NUTRITION
74. A-10, B-5, C-8, D-1, E-7, F-6, G-12, H-13, I-11, J-2, K-9, L-3, M-4.
75. Zinc.
76. Ethanol metabolism converts NAD+ into NADH, which causes many of the symptoms of chronic
alcohol abuse.
METABOLISM
77. A-10, B-7, C-3, D-4, E-1, F-9, G-13, H-5, I-8, J-6, K-11, L-12, M-2.
78.
Glucose
Glucose-6-P
Fructose-6-P
Citrate
Oxaloacetate
Fructose-1,6-BP
Isocitrate
Malate
Glyceraldehyde- Fumarate α-
3-P ketoglutarat
Succinate Succinyl-CoA
1,3-BPG
3-
phosphoglycerate
2-
phosphoglycerate
PEP
Pyruvate
PDH
Acetyl-CoA
79. Aerobic glucose metabolism produces 32 ATP molecules per molecule of glucose in heart and liver
and 30 in muscle. Anaerobic glucose metabolism products only 2 net ATP molecules per molecule
of glucose.
80. Vitamins B1, B2, B3, and B5, and lipoic acid.
82. Heinz bodies are clumps of denatured hemoglobin precipitates that stick to an RBC’s membrane.
When the RBC passes through the spleen, macrophages remove the Heinz bodies, which make
the cell look as if a bite were taken out of it.
83.
84. Ornithine transcarbamylase deficiency. (Orotic aciduria does not have hyperammonemia and often
presents with megaloblastic anemia.)
85.
87.
Accumulated
Disease Deficient Enzyme
Substance(s)
Heparan sulfate,
Hunter syndrome Iduronate sulfatase
dermatan sulfate
Heparan sulfate,
Hurler syndrome α-L-iduronidase
dermatan sulfate
Metachromatic
Arylsulfatase A Cerebroside sulfate
leukodystrophy