1. A 2-year-old Caucasian male is being evaluated for progressive
neurological deterioration. Laboratory evaluation, including
leukocyte enzyme activity analysis, suggests Niemann-Pick
disease. This patient most likely has a deficiency of which of the
following enzymes?
A. Arylsulfatase A
B. beta -hexosaminidase A
C. alpha- galactosidase
D. Beta-glucosidase
E. Neuraminidase
F. Sphingomyelinase
G. Ceramidase
Answer: F
Explanation:
Niemann-Pick disease Type A is an autosomal recessive disorder most
common in individuals of Ashkenazi Jewishdescent. Affected infants
present in the first year of life with hepatosplenomegaly and progressive
hypotonia and mental retardation following a period of normal early
development. The cause is deficiency of the sphingomyelinase enzyme,
which in normal individuals is responsible for cleaving sphingomyelin into
phosphorylcholine and ceramide. In infants with Niemann-Pick disease,
sphingomyelin accumulates within phagocytes, producing characteristic
"foamy histiocytes." These foamy-appearing, sphingomyelin-laden
histiocytes accumulate in the liver and spleen caus:ing massive
hepatosplenomegaly. Progressive sphingomyelin accumulation in the
central nervous system is responsible for the neurologic degeneration
that occurs. Sphingomyelin deposition in the retina causes blindness as
well. A cherry-red macular spot, similar to that seen in Tay-Sachs
disease, is also often found. Death usually occurs before age three.
(Choice A) In patients with the autosomal recessive condition
metachromatic leukodystrophy, a deficiency of the enzyme arylsulfatase
A causes sulfatides to accumulate within tissues.
,(Choice B) In the autosomal recessive condition Tay-Sachs disease, a
deficiency of the enzyme 13- hexosaminidase A causes ganglioside to
accumulate within neurons.
(Choice C) In Fabry disease, an X-linked recessive condition,
deficiency of the enzyme a-galactosidase A causes ceramide
trihexoside to accumulate in tissues.
(Choice D) 13-Glucosidase is a plant enzyme used for the breakdown
of starch.
(Choice E) Neuraminidase (sialidase} deficiency is the cause of human
sialidosis. Neuraminidase is also a surface enzyme found on the
influenza virus.
(Choice G) Ceramidase deficiency causes Farber disease, an
autosomal recessive condition characterised by ceramide accumulation
within neurons and within granulomas in the skin.
2. A diagram illustrating the DNA replication process is shown below.
Which of the points marked by letters represents the site of action of
helicase in the following diagram?
, A. A
B. B
C. C
D. D
E. E
Answer: E
Explanation:
DNA replication occurs during the S-phase (synthesis phase) of
the cell cycle. Replication of the genome is performed by the coordinated
effects of more than thirty proteins to ensure that the daughter strands
are the exact replica of the parent strands. DNA polymerases are the
main enzymes responsible for the synthesis of new strands of DNA. In
E. coli, there are three major types of DNA polymerases: I, II and Ill. In
prokaryotes, DNA polymerase Ill performs the bulk of the DNA
replication (Choice C).
DNA polymerases form new daughter strands in the 5' to 3' direction
using the parent strand as a template. DNA replication can only occur on
single stranded DNA; therefore, unwinding and dissociation of the parent
DNA strands is necessary before replication can proceed. First, the
origin of replication is identified and bound by several monomers of the
DnaA protein which serves to locally dissociate double stranded DNA
, (dsDNA) into single stranded DNA (ssDNA) at the origin of replication.
Single strand binding proteins (SSBs, Choice D) then bind to the ssDNA
and stabilise it, preventing premature reannealing of the ssDNA to
dsDNA. Helicase (Choice E) then binds the ssDNA at the origin of
replication, moves into the replication fork, and then proceeds to
separate and unwind the dsDNA.
The topoisomerase enzymes (not pictured) include topoisomerase I and
II, which relieve supercoiling tension of the dsDNA strand caused by the
unwinding action of helicase. Topoisomerase II is also known as gyrase
in prokaryotes. If pictured on the above diagram, these proteins would
be ahead of helicase on the dsDNA segment.
DNA polymerases synthesises new DNA strands in the 5' to 3' direction
and require a free 3'-hydroxyl group upon which to begin polymerization.
This 3'-hydroxyl group is provided by the enzyme primase, a DNA-
dependent RNA polymerase which forms RNA primers (Choice A). Both
daughter strands are not produced continuously; the strand that forms
continuously from the 5' to the 3' direction is called the leading strand
(upper strand in the above diagram), and the second strand, the lagging
strand, is generated by the formation of short fragments called Okazaki
fragments (lower strand on the above diagram) in the 5' to 3' direction.
The fragments of the lagging strand are bound together by the enzyme
ligase (Choice B).
3. A 22-year-old Caucasian female is brought to urgent care w ith acute
onset abdominal pain, nausea, and confusion. She has had several
minor episodes of abdominal pain which correlate with drinking alcohol.
Serum lipase, liver function tests, and CT scan of the abdomen shows
no abnormalities. Her urine is normal in colour but turns dark upon
standing. Intravenous dextrose administered to this patient improves her
symptoms. High-dose glucose infusion significantly improves this
patient's condition by affecting:
A. Blood glucose level
neurological deterioration. Laboratory evaluation, including
leukocyte enzyme activity analysis, suggests Niemann-Pick
disease. This patient most likely has a deficiency of which of the
following enzymes?
A. Arylsulfatase A
B. beta -hexosaminidase A
C. alpha- galactosidase
D. Beta-glucosidase
E. Neuraminidase
F. Sphingomyelinase
G. Ceramidase
Answer: F
Explanation:
Niemann-Pick disease Type A is an autosomal recessive disorder most
common in individuals of Ashkenazi Jewishdescent. Affected infants
present in the first year of life with hepatosplenomegaly and progressive
hypotonia and mental retardation following a period of normal early
development. The cause is deficiency of the sphingomyelinase enzyme,
which in normal individuals is responsible for cleaving sphingomyelin into
phosphorylcholine and ceramide. In infants with Niemann-Pick disease,
sphingomyelin accumulates within phagocytes, producing characteristic
"foamy histiocytes." These foamy-appearing, sphingomyelin-laden
histiocytes accumulate in the liver and spleen caus:ing massive
hepatosplenomegaly. Progressive sphingomyelin accumulation in the
central nervous system is responsible for the neurologic degeneration
that occurs. Sphingomyelin deposition in the retina causes blindness as
well. A cherry-red macular spot, similar to that seen in Tay-Sachs
disease, is also often found. Death usually occurs before age three.
(Choice A) In patients with the autosomal recessive condition
metachromatic leukodystrophy, a deficiency of the enzyme arylsulfatase
A causes sulfatides to accumulate within tissues.
,(Choice B) In the autosomal recessive condition Tay-Sachs disease, a
deficiency of the enzyme 13- hexosaminidase A causes ganglioside to
accumulate within neurons.
(Choice C) In Fabry disease, an X-linked recessive condition,
deficiency of the enzyme a-galactosidase A causes ceramide
trihexoside to accumulate in tissues.
(Choice D) 13-Glucosidase is a plant enzyme used for the breakdown
of starch.
(Choice E) Neuraminidase (sialidase} deficiency is the cause of human
sialidosis. Neuraminidase is also a surface enzyme found on the
influenza virus.
(Choice G) Ceramidase deficiency causes Farber disease, an
autosomal recessive condition characterised by ceramide accumulation
within neurons and within granulomas in the skin.
2. A diagram illustrating the DNA replication process is shown below.
Which of the points marked by letters represents the site of action of
helicase in the following diagram?
, A. A
B. B
C. C
D. D
E. E
Answer: E
Explanation:
DNA replication occurs during the S-phase (synthesis phase) of
the cell cycle. Replication of the genome is performed by the coordinated
effects of more than thirty proteins to ensure that the daughter strands
are the exact replica of the parent strands. DNA polymerases are the
main enzymes responsible for the synthesis of new strands of DNA. In
E. coli, there are three major types of DNA polymerases: I, II and Ill. In
prokaryotes, DNA polymerase Ill performs the bulk of the DNA
replication (Choice C).
DNA polymerases form new daughter strands in the 5' to 3' direction
using the parent strand as a template. DNA replication can only occur on
single stranded DNA; therefore, unwinding and dissociation of the parent
DNA strands is necessary before replication can proceed. First, the
origin of replication is identified and bound by several monomers of the
DnaA protein which serves to locally dissociate double stranded DNA
, (dsDNA) into single stranded DNA (ssDNA) at the origin of replication.
Single strand binding proteins (SSBs, Choice D) then bind to the ssDNA
and stabilise it, preventing premature reannealing of the ssDNA to
dsDNA. Helicase (Choice E) then binds the ssDNA at the origin of
replication, moves into the replication fork, and then proceeds to
separate and unwind the dsDNA.
The topoisomerase enzymes (not pictured) include topoisomerase I and
II, which relieve supercoiling tension of the dsDNA strand caused by the
unwinding action of helicase. Topoisomerase II is also known as gyrase
in prokaryotes. If pictured on the above diagram, these proteins would
be ahead of helicase on the dsDNA segment.
DNA polymerases synthesises new DNA strands in the 5' to 3' direction
and require a free 3'-hydroxyl group upon which to begin polymerization.
This 3'-hydroxyl group is provided by the enzyme primase, a DNA-
dependent RNA polymerase which forms RNA primers (Choice A). Both
daughter strands are not produced continuously; the strand that forms
continuously from the 5' to the 3' direction is called the leading strand
(upper strand in the above diagram), and the second strand, the lagging
strand, is generated by the formation of short fragments called Okazaki
fragments (lower strand on the above diagram) in the 5' to 3' direction.
The fragments of the lagging strand are bound together by the enzyme
ligase (Choice B).
3. A 22-year-old Caucasian female is brought to urgent care w ith acute
onset abdominal pain, nausea, and confusion. She has had several
minor episodes of abdominal pain which correlate with drinking alcohol.
Serum lipase, liver function tests, and CT scan of the abdomen shows
no abnormalities. Her urine is normal in colour but turns dark upon
standing. Intravenous dextrose administered to this patient improves her
symptoms. High-dose glucose infusion significantly improves this
patient's condition by affecting:
A. Blood glucose level
