Page 1 of 1: LIST OF QUESTIONS FOR PRACTICE REGARDING CELL BIOLOGY

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A 6-month-old boy is brought to the pediatrician by his parents, who are first cousins. This is their
first child. Physical examination reveals a small, thin, lethargic infant with slightly misshapen
long bones. His features are somewhat coarse. Joint movements are restricted, his corneas are
clouded, and his gums are underdeveloped. His liver is not enlarged. Serum levels of acid
hydrolases are found to be elevated. The child most likely has a defect in which of the following
metabolic activities?

A. Degradation of dermatan sulfate and heparan sulfate

B. Degradation of gangliosides

C. Degradation of glycogen

D. Degradation of sphingomyelin

E. Phosphorylation of mannose moieties

F. Phosphorylation of tyrosine moieties

Explanation:

The correct answer is E. The patient has I-cell disease, also known as mucolipidosis II, which is
due to a defective UDP-N-acetylglucosamine-1-phosphotransferase, the enzyme that phosphorylates
mannose on enzymes destined for lysosomes. Proteins coded by nuclear DNA are synthesized on
cytoplasmic ribosomes, which may be either "free" or associated with the endoplasmic reticulum to
form the rough endoplastic reticulum (RER). Proteins synthesized on the RER are transferred into
the Golgi apparatus, where they undergo further modifications that determine whether they remain
part of the Golgi apparatus, become part of the plasma membrane, or are shipped to lysosomes or
mitochondria. Proteins not marked for transport to a specific intracellular site follow the
default pathway and are exported into the extracellular compartment. The signal for transport of
the acid hydrolases (and probably other enzymes) to the lysosomes is phosphorylation of a

terminal mannose moiety on an N-linked oligosaccharide to form mannose 6-phosphate. In I-cell
disease, this terminal mannose moiety is not phosphorylated, and the acid hydrolases follow the
default pathway and are secreted.

Deficiency of alpha-L-iduronidase results in lysosomal accumulation of dermatan sulfate and
heparan sulfate (choice A) in several conditions such as mucopolysaccharidosis I, Hurler's
disease, or Hurler's/Scheie disease.

Hexosaminidase A deficiency (Tay-Sachs disease) is one example of a condition in which
ganglioside accumulation occurs (choice B).

There are a number of diseases in which glycogen degradation (choice C) is defective. These are
collectively termed glycogen storage diseases since they result in abnormal cellular accumulation
of glycogen. In Pompe's disease, or type II glycogen storage disease, a lysosomal glucosidase is
deficient, resulting in lysosomal glycogen accumulation.

Deficiency of sphingomyelinase (choice D), an enzyme involved in degradation of sphingomyelin,
results in Niemann-Pick disease.

Phosphorylation of tyrosine moieties (choice F) is unrelated to lysosomes or lysosomal enzymes;
however, decreased ability to phosphorylate tyrosine moieties might be associated with diabetes
or dwarfism.

2

A cell that produces glycoproteins that contain 8-9 mannose residues per sugar chain has a glycosylation
enzyme defect in which of the following organelles?

A. Endoplasmic reticulum

B. Golgi apparatus

C. Lysosomes

D. Mitochondria

E. Plasma membrane

Explanation:

The correct answer is B. An oligosaccharide chain containing 9 mannoses is transferred from a
dolichol carrier to the asparagine in an asn-X-ser/thr sequence during N-linked sugar assembly.
This step occurs in the rough endoplasmic reticulum (choice A). The trimming of mannoses down
to 5 residues occurs in the Golgi apparatus prior to the addition of complex sugars. A defect
in one of the Golgi mannosidases would produce high-mannose sugar chains.

No glycosylation occurs in the lysosomes (choice C), mitochondria (choice D), or plasma
membrane (choice E).

3

Molecular genetic studies are performed on a family with known familial hypercholesterolemia. In this
particular family, the defect in the LDL receptor gene involves a messenger mutation near the
11th exon, in the region of homology with epidermal growth factor receptor precursor. A defect
at this site would be most likely to produce which of the following effects?

A. Decreased transcription of LDL receptor gene

B. Poor internalization of LDL bound to LDL receptor

C. Poor retention of the LDL receptor in the membrane

D. Reduced binding of LDL

E. Trapping of the LDL receptor in the endoplasmic reticulum

Explanation:

The correct answer is E. Familial hypercholesterolemia, which is due to defective function of
the LDL receptor, is an area of intense research. The molecular basis of LDL receptor
abnormalities is becoming better understood, and more than 200 mutations in the gene for the LDL
receptor have been identified. The gene has 5 general domains and 18 exons. Defects near exons 7
to 14 (including this case) are in the region of homology with epidermal growth factor receptor
precursor. This region of the molecule is needed for dissociation of LDL from the receptor in
the endosome. Receptors with a defect in this area (sometimes called class II mutations) also
have trouble being initially transported to the Golgi complex (transport-deficiency alleles) and
become trapped in endoplasmic reticulum.

Decreased transcription of the LDL receptor gene (choice A) is considered a class I mutation and
involves the signal sequence domain near exon 1.

Poor internalization of LDL bound to LDL receptor (choice B) is considered a class IV mutation.
Such mutations are associated with the membrane-spanning/cytoplasmic domain, specifically near
exon 18.

Poor retention of the LDL receptor in the membrane (choice C) is considered a class IV
mutation
and is associated with the membrane-spanning/cytoplasmic domain, specifically near exons 2-6.

Reduced binding of LDL (choice D) is considered a class III mutation and involves the LDL
binding domain near exons 2-6.

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4 In order to study calcium fluxes in living cells, a researcher employs fluorescent calcium indicators
and laser scanning confocal microscopy. In her experiments, she stimulates smooth muscle cells using a
variety of pharmacological agents, then videotapes the calcium fluxes in the cell in real time using the
confocal microscope. Which of the following drugs would most likely produce the strongest calcium signal
in the smooth muscle cells?

A. Clonidine

B. Isoproterenol

C. Phentolamine

D. Phenylephrine

E. Timolol

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Explanation:

The correct answer is D. Two pieces of information are necessary to answer this question. First,
you must know the drug classes represented by the answer choices. Second, you must know what
second messengers are associated with these receptors. Phenylephrine is an α1 agonist;
α1 receptors are coupled to Gq, which stimulates phospholipase C (PLC), leading to
hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2), a phospholipid in the plasma
membrane. PIP2 is split into two second messengers: inositol-1,4,5-triphosphate (IP3) and
diacylglycerol. IP3 diffuses through the cytoplasm to internal storage sites, where it triggers
the release of calcium, thus providing the signal for this experiment. Diacylglycerol remains in
the membrane and activates protein kinase C.

Clonidine (choice A) is an α2 agonist. α2 receptors are coupled to Gi, which
inhibits adenylate cyclase, leading to decreases in intracellular cAMP levels.
Isoproterenol (choice B) is a nonselective β agonist. All β receptors are coupled to
Gs, which stimulates adenylate cyclase, leading to elevated intracellular cAMP levels.

Phentolamine (choice C) is a nonselective α antagonist. This drug would prevent the
increase in calcium caused by stimulation of α1 receptors.

Timolol (choice E) is a nonselective β antagonist. This drug would prevent β-induced
increases in cAMP.

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5 A rapid way to purify proteins that are targeted to the lysosomes would be to use affinity
chromatography. An appropriate antibody to use on an affinity chromatography column would be one
directed against

A. acid hydrolases

B. clathrin

C. glucose-6-phosphate

D. mannose-6-phosphate

E. sialic acid

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Explanation:

The correct answer is D. Proteins that are targeted for lysosomes have mannose-6-phosphate on
their sugar chains. The mannose-6-phosphate is on an external site on the protein so that it
can be recognized by the mannose-6-phosphate receptor on the lysosomal surface, and would also
be easily accessible to an antibody directed against it.

Acid hydrolases (choice A) are enzymes found inside the lysosomes.

Coated pits (the cellular site for receptor-mediated endocytosis) contain clathrin (choice B).

Production of glucose-6-phosphate (choice C) from glucose is the first step in the process of
glycolysis.

Sialic acid (choice E) is a terminal glycosylation product added to proteins (usually those
destined for secretion) in the Golgi apparatus.

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6 Liver cells in culture were kept at 0°C and treated with trypsin to digest the receptors on the cell
surface. The temperature was then raised to 37°C and radioactive LDL was added to the culture media.
Several hours later, the labeled LDL was found to be inside the cells. This specific process of LDL
uptake is
A. active transport

B. facilitated diffusion

C. phagocytosis

D. pinocytosis

E. receptor-mediated endocytosis

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Explanation:

The correct answer is E. Even though the surface LDL receptors were digested by the trypsin,
the recycling of unoccupied receptors to the cell surface provides a continual supply of new
receptors to bind the labeled LDL. The LDL-receptor complex is internalized by receptor-
mediated endocytosis.

Active transport (choice A) is the energy-dependent movement of molecules across a membrane and
against a concentration gradient.

Facilitated diffusion (choice B) is the transport of low-permeability molecules with the aid of
a carrier protein.

Phagocytosis (choice C) is the process by which cells such as macrophages and neutrophils
engulf large particles.

Pinocytosis (choice D) is the uptake of small molecules in solution, and is receptor
independent.

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