nishi's qb - biochemistry
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* biochem
#128673nishi - 10/15/06 19:39
A chronic alcoholic develops severe memory loss with
marked confabulation. Deficiency of which of the
following vitamins would be most likely to contribute tothe neurologic damage underlying these
symptoms?
A. Folic acid
B. Niacin
C. Riboflavin
D. Thiamine
E. Vitamin B12
Explanation:
The correct answer is D. Wernicke-Korsakoff syndrome
refers to the constellation of neurologicsymptoms caused by thiamine deficiency. Among these,
a severe memory deficit, which the patient may
attempt to cover by making up bizarre explanations(confabulation), is prominent. Anatomical damage
to the mamillary bodies and periventricular structures
has been postulated as the cause. In theU.S., severe thiamine deficiency is seen most commonly
in chronic alcoholics. Thiamine deficiency
can also damage peripheral nerves ("dry" beriberi) andthe heart ("wet" beriberi).
Folic acid deficiency (choice A) produces megaloblasticanemia without neurologic symptoms.
Niacin deficiency (choice B) produces pellagra,characterized by depigmenting dermatitis, chronic
diarrhea, and anemia.
Riboflavin deficiency (choice C) produces ariboflavinosis,characterized by glossitis, corneal
opacities, dermatitis, and erythroid hyperplasia.
Vitamin B12 deficiency (choice E) produces
megaloblastic anemia accompanied by degeneration of
theposterolateral spinal cord.
A 25-year-old woman with sickle cell anemia complains
of steady pain in her right upper quadrant withradiation to the right shoulder, especially after large or
fatty meals. Her physician diagnoses
gallstones. Of which of the following compounds are
these stones most likely composed?
A. Calcium bilirubinate
B. Calcium oxalate
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C. Cholesterol
D. Cholesterol and calcium bilirubinate
E. Cystine
Explanation:
The correct answer is A. Bilirubin is a degradative
product of hemoglobin metabolism. Bilirubin(pigment) stones are specifically associated with
excessive bilirubin production in hemolyticanemias, including sickle cell anemia. Bilirubin stones
can also be seen in hepatic cirrhosis andliver fluke infestation.
Calcium oxalate stones (choice B) and cystine stones(choice E) are found in the kidney, rather than
the gallbladder.
Pure cholesterol stones (choice C) are less common thanmixed gallstones, but have the same risk
factors, including obesity and multiple pregnancies.
Mixed stones (choice D) are the common "garden
variety" gallstones, found especially in obese,
middle aged patients, with a female predominance.
Two sisters are diagnosed with hemolytic anemia. Their
older brother was previously diagnosed with thesame disorder. Two other brothers are asymptomatic.
The mother and father are second cousins.
Deficiency of which of the following enzymes would bemost likely to cause this disorder?
A. Debranching enzyme
B. Glucose-6-phosphatase
C. Glucose-6-phosphate dehydrogenase
D. Muscle phosphorylase
E. Pyruvate kinase
Explanation:
The correct answer is E. In general, you should associate
hemolytic anemia with defects inglycolysis or the hexose monophosphate shunt (pentose
phosphate pathway). Only two enzymes of those
listed in the answer choices specifically involve these
pathways and cause hemolytic anemia:pyruvate kinase and glucose-6-phosphate
dehydrogenase. Glucose-6-phosphate dehydrogenase
(G6PD)
deficiency is inherited as an X-linked recessive trait, so
females would not be affected. Pyruvatekinase is a glycolytic enzyme; pyruvate kinase deficiency
is an autosomal recessive disorder,affecting males and females approximately equally. If
this enzyme is deficient, red cells have
trouble producing enough ATP to maintain the Na+/K+pump on the plasma membrane, secondarily causing
swelling and lysis.
Debranching enzyme (choice A) defects produce Cori's
disease, one of the glycogen storage diseases.
Defects in glucose-6-phosphatase (choice B) produce
Von Gierke's disease, one of the glycogen
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storage diseases.
Glucose-6-phosphatase dehydrogenase (choice C)deficiency produces an X-linked hemolytic anemia.
Defects in muscle phosphorylase (choice D) produce
McArdle's disease, one of the glycogen storagediseases.
Which of the following amino acids would most likely befound on the surface of a protein molecule?
A. Alanine
B. Arginine
C. Isoleucine
D. Leucine
E. Phenylalanine
F. Tryptophan
Explanation:
The correct answer is B. This question requires twological steps: first, you need to appreciate
that the hydrophilic amino acids are more likely to
appear on the surface of a protein molecule,while hydrophobic amino acids are most likely be found
in its interior. Next, you need to figure out
which of the amino acids listed is hydrophilic. If yourecall that arginine is a basic amino acid
that is positively charged at physiologic pH, you should
be able to answer this question right away.
All of the other choices have neutral side chains and are
uncharged at physiologic pH. They wouldmost likely be found in the hydrophobic core of the
protein structure. Alanine (choice A),
isoleucine (choice C), and leucine (choice D) all havealiphatic side chains; phenylalanine (choice
E) and tryptophan (choice F) have aromatic side chains.
A Southeast Asian immigrant child is noted to beseverely retarded. Physical examination reveals a pot-
bellied, pale child with a puffy face. The child's tongue is
enlarged. Dietary deficiency of whichof the following substances can produce this pattern?
A. Calcium
B. Iodine
C. Iron
D. Magnesium
E. Selenium
Explanation:
The correct answer is B. The disease is cretinism,
characterized by a profound lack of thyroid
hormone in a developing child, leading to mentalretardation and the physical findings described in
the question stem. Cretinism can be due to dietary
deficiency of iodine (now rare in this countrybecause of iodized salt), to developmental failure of
thyroid formation, or to a defect in thyroxine
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synthesis.
Calcium deficiency (choice A) in children can causeosteoporosis or osteopenia.
Iron deficiency (choice C) can cause a hypochromic,
microcytic anemia.
Magnesium deficiency (choice D) is uncommon, but can
cause decreased reflexes, and blunts theparathyroid response to hypocalcemia.
Selenium deficiency (choice E) is rare, but may cause a
reversible form of cardiomyopathy.
To which of the following diseases is pyruvate kinase
deficiency most similar clinically?
A. -thalassemia
B. -thalassemia
C. Glucose-6-phosphate dehydrogenase deficiency
D. Hereditary spherocytosis
E. Iron deficiency anemia
Explanation:
The correct answer is C. Both pyruvate kinase deficiency
and glucose-6-phosphate dehydrogenase
deficiency are red cell enzyme deficiencies characterizedclinically by long "normal" periods
interspersed with episodes of hemolytic anemia
triggered by infections and oxidant drug injury(antimalarial drugs, sulfonamides, nitrofurans). In both
of these conditions, the cell morphology
between hemolytic episodes is usually normal or close tonormal.
The (choice A) and (choice B) thalassemias, in theirmajor forms, are characterized by
persistent severe anemia. In the trait forms, they are
charactertized by mild anemia.
Hereditary spherocytosis (choice D) is characterized by
intermittent hemolysis, but, unlike pyruvate
kinase deficiency and glucose-6-phosphatedehydrogenase deficiency, oxidant drugs are not a
specific
trigger for hemolysis.
Iron deficiency anemia (choice E) is characterized by
chronic anemia with hypochromic, microcytic
erythrocytes.
A baby that was apparently normal at birth begins toshow a delay in motor development by 3 months of
age. At one year of age, the child begins to developspasticity and writhing movements. At age three,
compulsive biting of fingers and lips and head-banging
appear. At puberty, the child developsarthritis, and death from renal failure occurs at age 25.
This patient's condition is due to an
enzyme deficiency in which of the following biochemicalpathways?
A. Ganglioside metabolism
B. Monosaccharide metabolism
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C. Purine metabolism
D. Pyrimidine metabolism
E. Tyrosine metabolism
Explanation:
The correct answer is C. The patient has a classical caseof Lesch-Nyhan syndrome, an X-linked
disorder due to severe deficiency of the purine salvageenzyme hypoxanthine-guanine phosphoribosyl
transferase (HPRT). This defect is associated withexcessive de novo purine synthesis,
hyperuricemia, and the clinical signs and symptoms
described in the question stem. The biochemicalbasis of the often striking self-mutilatory behavior
(which may require restraints and even tooth
extraction) has never been established. Treatment with
allopurinol inhibits xanthine oxidase andreduces gouty arthritis, urate stone formation, and urate
nephropathy. It does not, however, modify
the neurologic/psychiatric presentation.
An obese individual is brought to the emergency room
by a concerned friend. The patient has been on aself-imposed "starvation diet" for four months, and has
lost 60 pounds while consuming only water
and vitamin pills. If extensive blood studies wereperformed, which of the following would be
expected to be elevated?
A. Acetoacetic acid
B. Alanine
C. Bicarbonate
D. Chylomicrons
E. Glucose
Explanation:
The correct answer is A. Long-term starvation inducesmany biochemical changes. Much of the body's
energy requirements are normally supplied by serum
glucose, but in starvation are supplied by bothglucose and lipid-derived ketone bodies, including
acetoacetic acid and beta-hydroxybutyric acid.
Glucose cannot be synthesized from lipids, and is
instead made from amino acids such as alanine inthe process of gluconeogenesis.
Serum alanine (choice B) drops dramatically in
starvation, due to its conversion to glucose.
Bicarbonate (choice C) levels drop as the bicarbonate
buffers the hydrogen ions produced by theketone bodies.
Chylomicrons (choice D) are the lipid form seen afterabsorption of dietary fat, and would drop
because the person is not feeding.
Glucose (choice E) is maintained in the blood at a much
lower than normal level during starvation.
A 15-year-old girl is seen by a dermatologist for removal
of multiple squamous cell carcinomas of the
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skin. The patient has nearly white hair, pink irises, very
pale skin, and a history of burning easily
when exposed to the sun. This patient's condition iscaused by a disorder involving which of the
following substances?
A. Aromatic amino acids
B. Branched chain amino acids
C. Glycolipids
D. Glycoproteins
E. Sulfur-containing amino acids
Explanation:
The correct answer is A. The disease is albinism. The
most common form of albinism is caused by a
deficiency of copper-dependent tyrosinase (tyrosinehydroxylase), blocking the production of melanin
from the aromatic amino acid tyrosine. Affected
individuals lack melanin pigment in skin, hair, andeyes, and are prone to develop sun-induced skin
cancers, including both squamous cell carcinomas and
melanomas.
Maple syrup urine disease is an example of a disorder of
branched chain amino acids (choice B)causing motor abnormalities and seizures.
Tay-Sachs disease is an example of a disorder ofglycolipids (choice C). In this disorder, a
deficiency of hexosaminidase A leads to accumulation of
ganglioside GM2.
Hunter's disease is an example of a disorder of
glycoproteins (choice D). This mucopolysaccharidosisis inherited as an autosomal recessive trait.
Homocystinuria disease is an example of a disorder ofsulfur-containing amino acids (choice E).
A 7-year-old boy is referred to a specialty clinic because
of digestive problems. He often experiencessevere abdominal cramps after eating a high fat meal.
He is worked up and diagnosed with a genetic
defect resulting in a deficiency of lipoprotein lipase.Which of the following substances would most
likely be elevated in this patient's plasma following a
fatty meal?
A. Albumin-bound free fatty acids
B. Chylomicrons
C. HDL
D. LDL
E. Unesterified fatty acids
Explanation:
The correct answer is B. After eating a high fat meal,triglycerides are processed by the intestinal
mucosal cells. They are assembled in chylomicrons and
eventually sent into the circulation fordelivery to adipocytes and other cells. Chylomicrons are
too large to enter cells, but are degraded
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while in the circulation by lipoprotein lipase. A defect in
this enzyme would result in the
accumulation of chylomicrons in the plasma.
Albumin-bound free fatty acids (choice A) is incorrect
because fatty acids leave the intestine
esterified as triglycerides in chylomicrons.
HDL (choice C) is not a carrier of dietary fat from the
intestine.
LDL (choice D) would be not be elevated in this patientafter a high fat meal. However, VLDL would
be elevated if the patient ate a high carbohydrate meal.In this situation, the carbohydrate would
be converted into fat in the liver and sent out into
circulation as VLDL. VLDL would be unable to bedegraded to LDL and, therefore, would accumulate.
A defect in lipoprotein lipase would cause a decrease,
not an elevation of unesterified fatty acids(choice E), since the chylomicrons contain esterified
fatty acids.
A 38-year-old man in a rural area presents to a
physician for an employment physical. Ocular
examinationreveals small opaque rings on the lower edge of the iris
in the anterior chamber of the eye. Nodular
lesions are found on his Achilles tendon. Successfultherapy should be aimed at increasing which of
the following gene products in hepatocyte cell
membranes?
A. Apo B-100
B. Apo B-100 receptor
C. Apo E
D. Apo E receptor
E. Lecithin cholesterol acyltransferase
Explanation:
The correct answer is B. This man has characteristic
signs of familial hypercholesterolemia, an
autosomal dominant disorder affecting about 1 in 500persons. The xanthomas on the Achilles tendon
and the arcus lipoides (the opaque rings in the eye) are
pathognomonic. Affected individuals have
very high LDL cholesterol because of deficientendocytosis of LDL particles by LDL receptors. These
receptors recognize the apo B-100 protein cotransported
with cholesterol esters in LDL. Treatments
aim at increasing genetic expression of LDL receptors
(i.e., apo B-100 receptors) to enhanceclearance of LDL particles. Dietary changes, a resin drug,
niacin, or an HMG-CoA reductase inhibitorcould be tried.
Apo B-100 (choice A) is the apoprotein of liver-producedlipoproteins such as VLDL, IDL and LDL. It
is therefore not in the hepatic cell membranes, and it
might be expected to decrease with decreasingconcentrations of circulating LDL.
Apo E (choice C) is an apoprotein found on VLDL, IDL,and chylomicrons, allowing "scavenging" by the
liver of remnants or of the lipoprotein itself. It is not
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found in the hepatocyte membrane.
Apo E receptor (choice D) would actually be increased bythe treatment with hypocholesterolemic
agents. However, the apo E receptor is not involved in
the scavenging of LDL particles.
Lecithin cholesterol acyl transferase (choice E) or LCAT,
is activated by apo AI, and esterifies
free cholesterol in plasma. Plasma levels of HDLcholesterol and apo AI are inversely related to the
risk of coronary heart disease.
Which of the following structures is common to allsphingolipids?
A. Carnitine
B. Ceramide
C. Diacylglycerol
D. Sphingomyelin
E. Squalene
Explanation:
The correct answer is B. Sphingolipids are a class of
lipids that are structural components ofmembranes. Ceramide is a component of sphingolipids.
Ceramide is composed of sphingosine, a long-
chain amino alcohol with a saturated fatty acid linked tothe amino group. Sphingolipids can be
differentiated on the basis of the "X" group that is
esterified to the terminal hydroxyl group ofceramide.
Carnitine (choice A) is involved in the oxidation of fattyacids. Carnitine is important in
transferring fatty acids from the cytoplasm into the
mitochondria (the carnitine shuttle).
Diacylglycerol (choice C) is the alcohol common to all
phospholipids. The second alcohol (e.g.,
choline, ethanolamine, serine) contributes the polarhead that d istinguishes the different classes
of phospholipids. Like sphingolipids, phospholipids are
found in membranes.
Sphingomyelin (choice D) is a sphingolipid with
phosphocholine as its "X" group. It is a component
of the myelin sheath.
Squalene (choice E) is a 30-carbon intermediate in the
synthesis of cholesterol.
A 47-year-old male patient presents with painfularthritis in the right big toe and uric acid renal
stones. He has been taking allopurinol for his condition.What biochemical defect would likely be
found in this patient?
A. A defect in urea synthesis
B. An abnormality of the purine degradation pathway
C. An inability to synthesize non-essential amino acids
D. Defective topoisomerases
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E. Increased levels of leukotrienes
Explanation:
The correct answer is B. This patient has gout,
characterized by painful joints due to the
precipitation of uric acid crystals caused by excessiveproduction of uric acid (a minority of cases
are associated with underexcretion of uric acid). Kidney
disease is also seen due to accumulation ofuric acid in the tubules. The disease mostly affects
males, and is frequently treated withallopurinol, an inhibitor of xanthine oxidase. Xanthine
oxidase catalyzes the sequential oxidationof hypoxanthine to xanthine to uric acid.
A defect in urea synthesis (choice A) would result in theaccumulation of ammonia.
Phenylketonuria is a disease in which tyrosine cannot be
produced from phenylalanine (choice C). Itis characterized by a musty body odor and mental
retardation.
Defective topoisomerases (choice D) would affect DNA
unwinding, and therefore replication.
Leukotrienes (choice E) are potent constrictors of
smooth muscle and would more likely lead to
bronchoconstriction.
A newborn vomits after each feeding of milk-based
formula, and does not gain weight. Biochemical testingreveals a severe deficiency of galactose-1-phosphate
uridyltransferase, consistent with homozygosity.
If this condition goes untreated, what is the likelyoutcome for this patient?
A. Benign disease except for cataract formation
B. Chronic emphysema appearing in early adulthood
C. Chronic renal failure appearing in adolescence
D. Death in infancy
E. Gastrointestinal symptoms that remit with puberty
Explanation:
The correct answer is D. Galactosemia occurs in two very
different clinical forms. Deficiency of
galactokinase produces very mild disease with the onlysignificant complication being cataract
formation. In contrast, homozygous deficiency of
galactose-1-phosphate uridyltransferase produces
severe disease culminating in death in infancy. In
addition to galactosemia and galactosuria, thesepatients have impaired renal tubular resorption leading
to aminoaciduria, gastrointestinal symptoms,hepatosplenomegaly, cataracts, bleeding diathesis,
hypoglycemia, and mental retardation.
Pathologically, the CNS shows neuronal loss and gliosisand the liver shows fatty change progressing
to cirrhosis.
Benign disease with cataract formation (choice A) is
characteristic of galactokinase deficiency.
Chronic emphysema (choice B) is not associated with
homozygous galactose-1-phosphate
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uridyltransferase deficiency, but rather with alpha
1-antitrypsin deficiency.
Impaired tubular reabsorption (producing
aminoaciduria) is seen within a few days or weeks of
feeding milk to an infant with severe galactosemia, as
opposed to chronic renal failure appearing inadolescence (choice C).
Gastrointestinal symptoms (choice E) certainly occur inhomozygous galactose-1-phosphate
uridyltransferase deficiency, but they would not beexpected to remit with puberty. Instead, most
untreated infants with this disorder show failure tothrive and die in infancy from wasting and
inanition.
A 20-year old female who is 2 months pregnant
remembers that she had phenylketonuria (PKU) as a
child
and required a special diet. Tests confirm markedlyelevated maternal serum levels of phenylalanine
and phenylacetic acid. Genetic studies have not been
performed on the father. What should thephysician tell the parents regarding the welfare of the
child?
A. Childhood phenylalanine restriction is sufficient to
protect the health of her child.
B. Further information is required to ascertain if the
fetus is at risk.
C. The fetus is at no health risk if it is heterozygous for
the PKU gene.
D. The fetus is at no health risk if phenylalanine levels
are normalized by the third trimester.
E. The mother's hyperphenylalaninemia may have
already harmed the fetus.
Explanation:
The correct answer is E. Phenylalanine crosses the
placenta and, if maternal serum levels areelevated, acts as a teratogen to the developing fetus.
This condition is known as maternal PKU.
Although the mother can fare well with substantialelevations in serum phenylalanine concentration,
the children born to such women are usually profoundly
retarded and may have multiple b irth defects.
Although dietary modifications (choice A) can prevent
the neurological and dermatologic
manifestations of PKU in a child, the fetus is still at risk
from maternal PKU.
Further information regarding the cause of this woman's
hyperphenylalaninemia (choice B) is notneeded, since the fetus is exposed to teratogenic levels
of phenylalanine.
Children born to mothers with untreated PKU develop
maternal PKU even if they are heterozygous for
the PKU gene (choice C). Fetal phenylalaninehydroxylase cannot compensate for the high maternal
levels of phenylalanine.
The critical period in development during which
teratogenic materials affect the growing organs is
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between the 3rd and 8th weeks of gestation. By the end
of the 2nd month (compare with choice D), the
damage caused by the maternal PKU has alreadyoccurred.
A 24-year-old graduate student presents to a physician
with complaints of severe muscle cramps andweakness with even mild exercise. Muscle biopsy
demonstrates glycogen accumulation, but hepatic
biopsy is unremarkable. Which of the following is themost likely diagnosis?
A. Hartnup's disease
B. Krabbe's disease
C. McArdle's disease
D. Niemann-Pick disease
E. Von Gierke's disease
Explanation:
The correct answer is C. A variety of glycogen storage
diseases exist, corresponding to defects in
different enzymes in glycogen metabolism; most ofthese involve the liver. McArdle's disease (Type V
glycogen storage disease), due to a defect in muscle
phosphorylase, is restricted to skeletalmuscle. The presentation described in the question stem
is typical. Many affected individuals also
experience myoglobinuria. Definitive diagnosis is basedon demonstration of myophosphorylase
deficiency.
Hartnup's disease (choice A) is a disorder of amino acid
transport.
Krabbe's disease (choice B) is a lysosomal storage
disease.
Niemann-Pick disease (choice D) is a lysosomal storage
disease.
Von Gierke's disease (choice E) is a glycogen storagedisease with prominent involvement of liver,
intestine, and kidney.
Which of the following metabolic processes occurs
exclusively in the mitochondria?
A. Cholesterol synthesis
B. Fatty acid synthesis
C. Gluconeogenesis
D. Glycolysis
E. Hexose monophosphate shunt
F. Ketone body synthesis
G. Urea cycle
Explanation:
The correct answer is F. Of the processes listed, onlyketone body synthesis occurs exclusively in
the mitochondria. Other mitochondrial processes include
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the production of acetyl-CoA, the TCA cycle,
the electron transport chain, and fatty acid oxidation.
Processes that occur exclusively in the cytoplasm include
cholesterol synthesis (choice A; in
cytosol or in ER), fatty acid synthesis (choice B),
glycolysis (choice D), and the hexosemonophosphate shunt (choice E).
Note that gluconeogenesis (choice C) and the urea cycle(choice G) occur in both the mitochondria
and the cytoplasm.
A physician from the United States decides to take asabbatical from his responsibilities at a teaching
hospital to work in a clinic in a remote part of Africa.
During his first week at the clinic, he istold that he will be seeing a patient with g lucose-
6-phosphate dehydrogenase deficiency. Which of the
following will be the most likely clinical presentation of
this patient?
A. A 6-month-old child who develops severe anemia
following a respiratory tract infection
B. A child who develops hemoglobinuria following a meal
of beans
C. A neonate with an enlarged spleen and severe anemia
D. An adult who develops anemia following use of
antimalarial drugs
E. An adult who develops severe shortness of breath
during an airplane ride
Explanation:
The correct answer is B. In Africa, the classicpresentation of glucose-6-phosphate dehydrogenase
deficiency is a child who eats a meal of beans (Vicia
fava) and several hours later developshemoglobinuria and peripheral vascular collapse
secondary to intravascular hemolysis as a result of
the oxidant injury initiated by the fava beans. Blood
studies in this setting show a rapid fall intotal hemoglobin and a rise in free plasma hemoglobin,
accompanied by a rise in unconjugated
bilirubin and a fall in haptoglobin. The episode usuallyresolves spontaneously several days later.
Today, the classic presentation is less common in
developed countries than is a slower onset
syndrome beginning 1-3 days after starting anantimalarial drug, sulfonamide, or other antioxidant
drug. Rarely, glucose-6-phosphate dehydrogenase
deficiency presents as neonatal jaundice or with
chronic hemolysis.
A patient with familial hypercholesterolemia undergoes a
detailed serum lipid and lipoprotein analysis.Studies demonstrate elevated cholesterol in the form of
increased LDL without elevation of other
lipids. This patient's hyperlipidemia is best classified aswhich of the following types?
A. Type 1
B. Type 2a
C. Type 2b
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D. Type 3
E. Type 5
Explanation:
The correct answer is B. Hyperlipidemia has beensubclassified based on the lipid and lipoprotein
profiles. Type 2a, which this patient has, can be seen in
a hereditary form, known as familialhypercholesterolemia, and also in secondary, acquired
forms related to nephritic syndrome andhyperthyroidism. The root problem appears to be a
deficiency of LDL receptors, which leads to aspecific elevation of cholesterol in the form of increased
LDL. Heterozygotes for the hereditary
form generally develop cardiovascular disease from 30 to50 years of age. Homozygotes may have
cardiovascular disease in childhood.
Type 1 (choice A) is characterized by isolated elevationof chylomicrons.
Type 2b (choice C) is characterized by elevations of bothcholesterol and triglycerides in the form
of LDL and VLDL.
Type 3 (choice D) is characterized by elevations of
triglycerides and cholesterol in the form of
chylomicron remnants and IDL.
Type 5 (choice E) is characterized by elevations of
triglycerides and cholesterol in the form ofVLDL and chylomicrons.
During the isolation of Met-enkephalin (Tyr-Gly-Gly-Phe-Met) from post-mortem human brain tissue,
researchers find that the peptide is rapidly degraded by
peptidases in 1 minute at 37 C. Detailedanalysis of the peptide cleavage pattern of
Met-enkephalin is investigated with two candidate
enzymes. Using the drug bestatin, the investigatorsfound no detectable Tyr-Gly-Gly-Phe-Met but did
find significant concentrations of Tyr-Gly-Gly. Using
thiorphan, there was no detectable Tyr-Gly-
Gly-Phe-Met, but there was a high concentration of Tyr.Which of the following is the best
conclusion about Met-enkephalin metabolism that can
be drawn from these data?
A. Bestatin inhibits an aminopeptidase, and thiorphan
inhibits an endopeptidase in the degradative
pathway
B. Bestatin inhibits a carboxypeptidase in the
degradative pathway
C. Bestatin inhibits an endopeptidase in the degradativepathway
D. Thiorphan inhibits an aminopeptidase, and bestatin
inhibits an endopeptidase in the degradative
pathway
E. Thiorphan inhibits an aminopeptidase in the
degradative pathway
Explanation:
The correct answer is A. Met-enkephalin, the most
abundant opioid peptide in the human brain, undergoes
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two routes of metabolism. One route releases a
tripeptide and therefore is the result of a peptidase
that cuts an amino acid bond within the molecule: anendopeptidase. The other route releases free
tyrosine and therefore is an exopeptidase. Exopeptidases
can remove amino acid residues from the amino-
or carboxyl-terminus of the protein. By convention, allpeptide sequences are given from the N to the C
terminus, the direction of translation. Tyrosine is
therefore at the amino-terminus of Met-enkephalin,and its release is the result of digestion by an
aminopeptidase.
The scientists have used two drugs to highlight the twoenzymatic pathways. With bestatin, Met-
enkephalin is metabolized only to the tripeptide;
therefore bestatin inhibits the aminopeptidaseenzyme, preventing release of free tyrosine residues.
With thiorphan, Met-enkephalin is metabolized to
free tyrosine; the tripeptide is no longer formed.
Thiorphan is an inhibitor of the endopeptidase. Thelack of persistence of Met-enkephalin in the presence of
an enzyme inhibitor is evidence that the
peptide's metabolism is shifted in the direction of thenoninhibited enzyme. A schematic of the
metabolism would be:
Tyrosine cannot be the result of carboxypeptidase
activity (choice B), since the carboxyl-terminus of
Met-enkephalin is a methionine.
Bestatin inhibits an aminopeptidase, not an
endopeptidase (choice C). An endopeptidase would notrelease a free amino acid residue.
Met-enkephalin is indeed metabolized by anaminopeptidase and an endopeptidase, but bestatin
inhibits
the aminopeptidase and thiorphan inhibits theendopeptidase (compare with choice D).
Thiorphan does not inhibit an aminopeptidase (choiceE); furthermore, such an enzyme would release a
free Tyr and a tetrapeptide.
The parents of a 6-month-old child who was normal atbirth bring her into the clinic. Since their
emigration to the U.S. from Eastern Europe soon after
her birth, the child has developed diminishedresponsiveness, progressive blindness and deafness, and
recently, seizures. Serum levels of which of
the following compounds would be expected to be
decreased in both of the parents?
A. Dystrophin
B. Hexosaminidase A
C. Hypoxanthine-guanine phosphoribosyltransferase
(HGPRT)
D. Phenylalanine hydroxylase
E. Vitamin D3
Explanation:
The correct answer is B. This patient has Tay-Sachs
disease, an autosomal recessive disorder causedby the deficiency of hexosaminidase A, which leads to
the accumulation of ganglioside GM2 in neurons,
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producing a degenerative neurologic disease. Children
appear normal at birth, but then begin to
suffer from diminished responsiveness, deafness,blindness, loss of neurologic function, and
seizures. A cherry-red spot on the macula may be seen
by ophthalmoscopic examination. Death usually
occurs by 4 to 5 years of age. There is no therapy. Theincidence is higher among Jews of Eastern
European descent. Since the parents must be
heterozygotes for the mutant hexosaminidase A allele,they would be expected to have diminished levels of the
enzyme.
A defect in the dystrophin (choice A) gene producesDuchenne muscular dystrophy, characterized by
onset of weakness in early childhood.
A severe deficiency in HGPRT (choice C) will lead to
Lesch-Nyhan syndrome, characterized by excessive
uric acid production, mental retardation, spasticity,
self-mutilation, and aggressive, destructivebehavior.
Deficiency of phenylalanine hydroxylase (choice D)results in classic phenylketonuria, a disease in
which phenylalanine, phenylpyruvate, phenylacetate,
and phenyllactate accumulate in plasma and urine.Clinically, there is a musty body odor and mental
retardation.
Hypophosphatemic rickets is an X-linked dominant
condition causing abnormal regulation of vitamin D3
(choice E) metabolism and defects in renal tubularphosphate transport. Symptoms include growth
retardation, osteomalacia, and rickets.
Poor oxygenation of tissues decreases the production of
ATP necessary for many cellular functions. Which
of the following processes is most immediatelycompromised in a typical cell when ATP production is
inadequate?
A. Complex carbohydrate synthesis
B. Lipid synthesis
C. Na+/K+ ATPase function
D. Nucleic acid synthesis
E. Protein synthesis
Explanation:
The correct answer is C. While ATP is important in
cellular synthetic functions, its role in
maintaining the Na+/ K+ exchange across the
plasmalemma is actually the most immediatelyimportant
function for most cells. The direct effect of this is theenergy (ATP) driven exchange of 3 Na+ ions
(which go from inside the cell to outside) for 2 K+ ions
(which go from outside to inside). Thisprocess requires considerable energy (1 ATP per
3Na+/2K+ exchange), since both the Na+ and K+ are
traveling against a concentration gradient. This directeffect of the Na+/ K+ ATPase may seem
trivial, but the secondary consequences are dramatic.
The Na+/ K+ ATPase helps establish thetransmembrane potential of the cell (because the
quantitatively uneven exchange of Na+/ K+ drives
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more positive ions out of the cell than in) and also both
the Na+ and K+ gradients. All of these
facilitate a wide variety of exchanges andtransmembrane transport systems that allow entry into
the
cell of the large variety of small molecules and ions that
it needs. The first microscopicallyvisible effect of significant hypoxia is cellular edema,
which is a consequence of distorted water
balance, also an indirect function of the Na+/ K+ATPase.
Urine screening of an apparently healthy pregnant
woman demonstrates a positive Clinitest reaction.However, blood glucose levels were within normal limits,
and more specific testing for urine glucose
is negative. The woman has been unaware of anymetabolic problems and has been living a normal life.
Deficiency of which of the following enzymes would most
likely produce this presentation?
A. Fructokinase
B. Fructose 1-phosphate aldolase
C. Galactose 1-P-uridyl transferase
D. Lactase
E. Pyruvate dehydrogenase
Explanation:
The correct answer is A. Glucose, galactose, and fructose
are all reducing sugars, and elevations of
all of these sugars can be detected with Clinitest tablets.Neither lactose nor pyruvate can be
detected, thus eliminating lactase and pyruvate
dehydrogenase as plausible choices. This leavesthree possibilities: fructokinase, fructose 1-phosphate
aldolase, and galactose 1-P-uridyl
transferases. Of these, only fructokinase deficiencyproduces a mild (usually completely
asymptomatic) condition known as fructosuria.
Fructose 1-phosphate aldolase deficiency (choice B)produces severe hereditary fructose intolerance.
Galactose 1-P-uridyl transferase deficiency (choice C)produces classic galactosemia.
Lactase deficiency (choice D) produces lactose
intolerance.
Pyruvate dehydrogenase deficiency (choice E) produces
severe disease (e.g., a subset of Leigh's
disease).
Addition of which of the following exhaustively 14C
labeled substrates would lead to evolution of 14CO2from a cell-free suspension containing all the enzymes
and substrates required for the synthesis of
uridylic acid?
A. Aspartate
B. Carbamoyl phosphate
C. Glutamine
D. Glycine
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E. N10-Formyltetrahydrofolate
Explanation:
The correct answer is A. In the first step of pyrimidinesynthesis, carbamoyl phosphate condenses
with aspartate to form carbamoyl aspartate, in a reaction
catalyzed by aspartate transcarbamoylase.
In subsequent steps, ring closure occurs with the loss ofwater, followed by oxidation to yield
orotic acid. Addition of ribose-5-phosphate producesorotidylic acid, which is decarboxylated by
orotidylate decarboxylase to yield uridylic acid. Thecarbon dioxide that is evolved is derived from
the alpha carboxyl group of aspartate.
Carbamoyl phosphate (choice B) condenses with
aspartate with the loss of inorganic phosphate to
produce carbamoyl aspartate. The carbamoyl moiety of
carbamoyl phosphate is retained.
Glutamine (choice C), glycine (choice D) and
N10-formyltetrahydrofolate (choice E) are all used inpurine synthesis. Glutamine also donates an amino
group to UTP to form CTP, but this step occurs
after the synthesis of uridylic acid is complete.
A histological section of the left ventricle of a deceased
28-year-old white male shows classiccontraction band necrosis of the myocardium. Biological
specimens confirm the presence of cocaine and
metabolites. Activity of which of the following enzymeswas most likely increased in the patient's
myocardial cells shortly prior to his death?
A. Phosphoenolpyruvate carboxykinase
B. Phosphofructokinase-1
C. Pyruvate dehydrogenase
D. Succinate dehydrogenase
E. Transketolase
Explanation:
The correct answer is B. Cocaine causes contractionband necrosis by blocking the reuptake of
norepinephrine, resulting in excessive vasoconstriction
of coronary vessels, leading to ischemia and
infarction of heart tissue. Under these pathologicalconditions, myocardial cells switch to anaerobic
metabolism and therefore glycolysis becomes the sole
source of ATP via substrate-level
phosphorylations by phosphoglycerate kinase and
pyruvate kinase. Phosphofructokinase-1 (PFK-1) is therate-limiting enzyme of glycolysis, and its activity would
therefore be increased.
Phosphoenolpyruvate carboxykinase (choice A) is a
regulatory enzyme in gluconeogenesis, which isinduced by cortisol, epinephrine, and glucagon. It
functions in the hepatic synthesis of glucose when
energy levels from beta-oxidation of fatty acids areadequate.
Pyruvate dehydrogenase (choice C) produces acetyl-CoAfrom pyruvate and coenzyme A, bridging
glycolysis and the Krebs cycle. It requires 5 cofactors,
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including NAD and FAD, which would no longer
be produced by the electron transport under hypoxic
conditions, decreasing its activity.
Succinate dehydrogenase (choice D) is a key enzyme of
the Krebs cycle, producing a reduced equivalent
of FAD to feed into the electron transport chain. It isalso known as Complex II. The Krebs cycle
only functions if oxygen is in appropriate concentrations
since it is regulated by the levels ofNADH, which is only consumed by the electron transport
chain if there is enough oxygen. The absenceof oxygen leads to an accumulation of NADH and a
subsequent decrease in the enzyme activities of theKrebs cycle.
Transketolase (choice E) is a thiamine requiring enzymeof the non-oxidative half of the hexose
monophosphate shunt. The shuffling of sugars in the
second half of this pathway results in the
reentry of glyceraldehyde-3-phosphate and fructose-6-phosphate into the glycolytic pathway.
Transketolase activity in red blood cells is used as a
clinical marker of thiamine deficiency,markedly decreasing in disorders such as Wernicke-
Korsakoff syndrome.
An 8-month-old child is brought to a pediatrician
because of the mother's concern about the boy's
tendency to compulsively bite his fingers. Onquestioning, the mother reported that she has noticed
yellow-orange crystals in his diapers, but has not
mentioned them to anyone. A genetic defect inwhich of the following pathways should be suspected?
A. Aromatic amino acid metabolism
B. Branched chain amino acid metabolism
C. Purine metabolism
D. Pyrimidine metabolism
E. Sulfur-containing amino acid metabolism
Explanation:
The correct answer is C. The disease is Lesch-Nyhan
syndrome, and the yellow-orange crystals of uricacid in the diaper are an important, but often neglected,
clue to early diagnosis. Lesch-Nyhan
syndrome is characterized by a tremendous
overproduction of purines, because the reutilization ofpurines via the purine salvage pathway is blocked by a
near total absence of hypoxanthine-guanine
phosphoribosyl-transferase (HGPRT) activity. Patients
with this severe X-linked disease, for reasons
that are unknown, show aggressive behavior that leadsto self-mutilation. They may also develop
gouty arthritis or gouty nephropathy.
Phenylketonuria is an example of a disorder of aromatic
amino acid metabolism (choice A)characterized by mental retardation.
Maple syrup urine disease is an example of a disorder ofbranched chain amino acids (choice B)
causing motor abnormalities and seizures.
Orotic aciduria is an example of a disorder of pyrimidine
metabolism (choice D), characterized by
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retarded growth and development as well as
megaloblastic anemia.
Homocystinuria is an example of a disorder of sulfur-
containing amino acids (choice E),
characterized by mental retardation, dislocation of the
lenses, osteoporosis, and thromboses.
Which of the following will be unchanged in a
Lineweaver-Burk plot of an enzyme with and without acompetitive inhibitor?
A. Km
B. Slope
C. x-intercept
D. y-intercept
Explanation:
The correct answer is D. It is worth taking the time to
learn how to read a Lineweaver-Burk plot.Lineweaver-Burk plots are used to determine the Vmax
and Km of an enzyme; they are also used to
differentiate between competitive and noncompetitiveinhibition.
Note that in a Lineweaver-Burk plot, the slope isKm/Vmax, the x-intercept is -1/Km, and the y-
intercept is 1/Vmax. In the presence of a competitive
inhibitor, the Km(choice A) and therefore theslope (choice B) are both increased. Similarly, if Km is
increased, -1/Km will become less negative
and the x-intercept will shift to the right. Intuitively,this makes sense since a competitive
inhibitor will increase the amount of substrate needed to
reach half-maximal velocity (definition ofKm). In contrast, the Vmax, and hence the y-intercept,
is unchanged (choice D).
Which of the following metabolic alterations would most
likely be present in a chronic alcoholic
compared to a non-drinker?
A. Fatty acid oxidation is stimulated
B. Gluconeogenesis is stimulated
C. Glycerophosphate dehydrogenase is stimulated
D. The ratio of lactate to pyruvate is decreased
E. The ratio of NADH to NAD+ is increased
Explanation:
The correct answer is E. The principal route of
metabolism of ethanol is via alcohol dehydrogenase,which uses hydrogen from ethanol to form NADH from
NAD+, markedly increasing the ratio of NADH to
NAD+. The relative excess of NADH has a number ofeffects, including inhibiting, rather than
stimulating fatty acid oxidation (choice A); inhibiting
gluconeogenesis rather than stimulating it(choice B); inhibiting, rather than stimulating (choice C)
glycerophosphate dehydrogenase; and
favoring the formation of lactate rather than pyruvatefrom glycolysis (thereby increasing, rather
than decreasing the lactate/pyruvate ratio; choice D).
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A couple brings in their 6-month-old child because they
are concerned about the child's inability to sitwithout support. The physician interviews the parents
and ascertains that they are both Ashkenazic
Jews. The doctor should inform them that, because oftheir heritage, their child may have an
increased risk of which of the following disorders?
A. Albinism and galactosemia
B. Cystic fibrosis and Lesch-Nyhan disease
C. Gaucher's disease and Tay-Sachs disease
D. Krabbe's disease and Niemann-Pick disease
E. Metachromatic leukodystrophy and phenylketonuria
Explanation:
The correct answer is C. You should associate Ashkenazic
(Eastern European) Jews with two diseases:
Tay-Sachs disease and Type I Gaucher's disease. Both ofthese diseases are sphingolipidoses. Tay-
Sachs disease is the more devastating of the two, and is
characterized by progressive neurologic(including visual) deterioration beginning at about 6
months of age and leading to death by age 3.
In contrast, Type I Gaucher's disease is compatible witha normal life span and causes
hepatosplenomegaly with CNS involvement. (The
infantile Type II and the juvenile Type III formscause more serious disease but are not seen with
increased incidence in Ashkenazic Jews.) None of
the other conditions listed occur with greater frequencyin Ashkenazic Jews. In this case, also note
that many perfectly normal children cannot sit without
support at 6 months of age, so the child maywell be healthy.
A 2-year-old retarded child is evaluated by a metabolicspecialist. The child's history is significant
for failure to thrive and progressive neurologic
deterioration, including deafness and blindness.
Physical examination is remarkable forhepatosplenomegaly, as well as a cherry-red spot on
funduscopic examination. These symptoms are
consistent with a diagnosis of
A. Hunter syndrome
B. Niemann-Pick disease
C. Pompe's disease
D. tyrosinosis
E. von Gierke's disease
Explanation:
The correct answer is B. Hepatosplenomegalyaccompanied by progressive neurologic deterioration
should make you think of lipid storage diseases;
Niemann-Pick disease is the only lipid storagedisease in the answer choices. Niemann-Pick disease is
due to a deficiency of sphingomyelinase,
leading to an accumulation of sphingomyelin. It is mostcommon among Ashkenazic Jews and generally
results in death by age 2. The cherry-red spot is also a
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characteristic of Tay-Sachs disease, but
hepatosplenomegaly suggests Niemann-Pick disease
rather than Tay-Sachs.
Hunter syndrome (choice A) is a mucopolysaccharidosis,
inherited in an X-linked recessive fashion.
Pompe's disease (choice C) is a glycogen storage
disease characterized by hypotonia and
cardiorespiratory failure.
Tyrosinosis (choice D) is a rare abnormality of tyrosinemetabolism that would not produce the
listed symptoms.
von Gierke's disease (choice E) is a severe form of
glycogen storage disease characterized byhypoglycemia, hepatomegaly, and renomegaly.
26
Which of the following enzymes is located at arrow 1 in
the electron micrograph above?
A. Carnitine acyltransferase II
B. Fatty acyl CoA synthetase
C. Glucose-6-phosphate dehydrogenase
D. Hexokinase
E. Pyruvate kinase
Explanation:
The correct answer is A. Arrow 1 indicates the inner
mitochondrial membrane. Carnitine acyltransferase
II is located on the inner face of the inner mitochondrialmembrane. It reforms fatty acyl CoA in the
mitochondrial matrix (arrow 5) from acyl carnitine, thus
preparing it for mitochondrial oxidation. Theacyl groups on carnitine are derived from acyl CoA esters
synthesized in the outer mitochondrial
membrane, which are made from free fatty acids
circulating in the blood.
Fatty acyl CoA synthetases (choice B) are located in the
outer mitochondrial membrane, indicated byarrow 2.
Glucose-6-phosphate dehydrogenase, the first enzyme
in the pentose phosphate pathway (choice C),hexokinase, the first enzyme in the glycolytic pathway
(choice D), and pyruvate kinase (choice E),
which produces pyruvate from phosphoenolpyruvate in
glycolysis, are all located in the cytosol,
indicated by arrow 3.
Arrow 4 indicates smooth endoplasmic reticulum.
A 72-year-old woman, in otherwise good health,
presents with megaloblastic anemia. Careful evaluationreveals a folate deficiency as the cause of the anemia.
Assuming the folate deficiency is due to
dietary causes, which of the following is the most likelyproblem?
A. Lack of leafy green vegetables
B. Lack of milk products
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C. Lack of red meat
D. Lack of yellow vegetables
E. Overcooked food
Explanation:
The correct answer is E. Folates (pteroylglutamic acidand related compounds) are widely distributed
in foodstuffs. Dietary deficiency is usually due toovercooked (folates are very labile) and old
(folates rapidly decay with time) food.
A 2-month-old boy is evaluated for failure to thrive. As
the pediatrician is examining the patient, shewitnesses a seizure. Physical examination is remarkable
for hepatomegaly, a finding later confirmed
by CT scan, which also reveals renomegaly. Serum
chemistries demonstrate severe hypoglycemia,hyperlipidemia, lactic acidosis, and ketosis. Which of the
following diseases best accounts for this
presentation?
A. Gaucher's disease
B. McArdle's disease
C. Niemann-Pick disease
D. Pompe's disease
E. von Gierke's disease
Explanation:
The correct answer is E. von Gierke's disease is a
glycogen storage disease caused by a deficiencyof glucose-6-phosphatase. It typically presents with
neonatal hypoglycemia, hyperlipidemia, lactic
acidosis, and ketosis. Failure to thrive is common inearly life; convulsions may occur due to
profound hypoglycemia. The glycogen accumulation in
von Gierke's disease occurs primarily in the
liver and kidneys, accounting for the enlargement ofthese organs. Gout may develop later because of
the derangement of glucose metabolism.
Even if you do not remember all of the details of the
presentation of these genetic diseases, you
should be able to narrow the choices:
Gaucher's disease (choice A) and Niemann-Pick disease
(choice C) are lipid storage diseases, and
would not be expected to produce hypoglycemia.
The other diseases are glycogen storage diseases, butMcArdle's (choice B) and Pompe's (choice D)
disease affect muscle rather than liver and would not beexpected to produce profound hypoglycemia,
since the liver is the major source for blood glucose.
A newborn appears normal at birth, but develops
vomiting and diarrhea accompanied by jaundice and
hepatomegaly within the first few weeks of life. Withinmonths, the baby has obvious cataracts and
ascites. The infant is switched to a milk-free diet, which
stabilizes but does not completely reversehis condition. By one year of age, he has developed
mental retardation. Which of the following is the
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most likely diagnosis?
A. Cystic fibrosis
B. Galactosemia
C. McArdle's disease
D. Von Gierke's disease
E. Wilson's disease
Explanation:
The correct answer is B. Galactosemia is an autosomal
recessive disease caused by a deficiency of
galactose-1-phosphate uridyltransferase, which isnecessary for the metabolism of the galactose
derived from milk lactose. The condition should be
suspected in infants with growth failure,
cataracts, liver disease, aminoaciduria, and mentalretardation. A reducing sugar (galactose) is
usually present in the urine. Most of the pathology is
related to the toxic effects of galactose-1-phosphate. Treatment involves strict dietary lactose
restriction, which consists of more than simply
withdrawal of milk products, because lactose is alsopresent in many non-diary foods. Strict
adherence to the diet can strikingly alter the course of
this disease.
Cystic fibrosis (choice A) is associated with
maldigestion, pancreatic disease, and pulmonarydisease.
McArdle's disease (choice C) is a glycogen storagedisease that selectively affects muscle.
Von Gierke's disease (choice D) is a glycogen storagedisease affecting the liver and kidneys.
Wilson's disease (choice E) is a caused by a metabolicabnormality in the handling of copper that
can cause cirrhosis and brain damage, and usually
presents in adolescence.
Which of the following pairs of enzymes is required for
the process of gluconeogenesis?
A. Fructose-1,6-bisphosphatase and pyruvate
carboxylase
B. Glucose-6-phosphatase and phosphofructokinase-1
C. Glucose-6-phosphatase and pyruvate dehydrogenase
D. Phosphoenolpyruvate carboxykinase and glucokinase
E. Pyruvate kinase and pyruvate carboxylase
Explanation:
The correct answer is A.The three irreversible steps ofglycolysis are catalyzed by hexokinase,
phosphofructokinase-1 (choice B), and pyruvate kinase.
In gluconeogenesis, other enzymes are neededto bypass these key steps. Pyruvate cannot be directly
converted to phosphoenolpyruvate in
gluconeogenesis. Therefore, pyruvate carboxylase (amitochondrial enzyme; choice A) converts pyruvate
to oxaloacetate, which can be converted to
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phosphoenolpyruvate by phosphoenolpyruvate
carboxykinase
(choice D), using two ATP equivalents per molecule ofphosphoenolpyruvate. Fructose-1,6-
bisphosphatase (choice A) is the enzyme that splits
fructose-1,6-bisphosphate into fructose-6-
phosphate and inorganic phosphate. It is also requiredfor gluconeogenesis.
Glucose-6-phosphatase (choices B and C) is a liverenzyme that hydrolyzes glucose-6-phosphate to
glucose. A deficiency of this enzyme leads to von Gierkedisease, also known as glycogen storage
disease type I.
Pyruvate dehydrogenase (choice C) is a mitochondrial
enzyme that converts pyruvate to acetyl CoA.This enzyme requires thiamine pyrophosphate,
lipoamide, and FAD as cofactors.
Glucokinase (choice D) is a liver enzyme that convertsglucose to glucose-6-phosphate. Unlike
hexokinase, it is specific for glucose and is unresponsive
to the level of glucose-6-phosphate. Itsfunction is to store excess glucose, so it has a very high
Km (ie, a low affinity) for glucose,
becoming active only when the concentration of glucoseis very high.
Pyruvate kinase (choice E) catalyzes the conversion ofphosphoenolpyruvate to pyruvate in the
glycolytic pathway. It is activated by fructose-
1,6-bisphosphate, the product of the committed stepof glycolysis, and is allosterically inhibited by ATP,
alanine, and acetyl CoA.
A 40-year-old, formerly obese woman presents to her
physician. She was very proud of having lost 80 lbs.
during the previous 2 years, but now noticed that her"hair is falling out." On questioning, she
reports having followed a strict fat-free diet. Her
alopecia is probably related to a deficiency ofwhich of the following vitamins?
A. Vitamin A
B. Vitamin C
C. Vitamin D
D. Vitamin E
E. Vitamin K
Explanation:
The correct answer is A. While it is hard to develop a
deficiency in oil-soluble vitamins (A, D, E,K) because the liver stores these substances, deficiency
states can be seen in chronic malnutrition(specifically chronic fat deprivation) and chronic
malabsorption. Vitamin A is necessary for
formation of retinal pigments (deficiency can causenight blindness) and for appropriate
differentiation of epithelial tissues (including hair
follicles, mucous membranes, skin, bone, andadrenal cortex).
Vitamin C (choice B), which is water soluble rather thanoil soluble, is necessary for collagen
synthesis.
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Vitamin D (choice C) is important in calcium absorption
and metabolism.
Vitamin E (choice D) is a lipid antioxidant that is
important in the stabilization of cellmembranes.
Vitamin K (choice E) is necessary for normal blood
coagulation.
5 mL of synovial fluid is aspirated from an inflamed kneejoint. The fluid is yellow-white and cloudy
and contains 200,000 WBC/mm3 (85% neutrophils).Needle-shaped, strongly negatively birefringent
crystals are seen both within and outside neutrophils.
These crystals most likely have which of thefollowing compositions?
A. Basic calcium phosphate
B. Calcium oxalate
C. Calcium pyrophosphate dihydrate
D. Cholesterol
E. Monosodium urate
Explanation:
The correct answer is E. All the compounds listed can
produce crystals in joint fluid, but onlymonosodium urate (associated with gout) and calcium
pyrophosphate dihydrate (associated with CPPD
crystal deposition disease, also called pseudogout), andto lesser degree basic calcium phosphate
(apatite-associated arthropathy), have a high likelihood
of being encountered on a step 1 USMLEexam. The crystals described are those of monosodium
urate. Be careful not to answer "uric acid" if
that is listed as an alternative choice on an exam, sincethe sodium salt is the predominant species
in vivo.
Basic calcium phosphate (choice A) is seen in apatite-associated arthropathy and produces spherical
clumps of nonbirefringent submicroscopic crystals.
Calcium oxalate crystals (choice B) are seen in primary
oxalosis and are bipyramidal, positively
birefringent crystals.
Calcium pyrophosphate dihydrate crystals (choice C) are
a feature of pseudogout and are rod-to-
rhomboidal-shaped, weakly positively birefringent
crystals.
Cholesterol crystals (choice D) are seen in chronic and
chylous effusions in inflammatory anddegenerative arthritis, where they form large, flat,
rhomboidal plates with notched corners.
Which of the following cofactors is required for
decarboxylation of alpha-ketoacids?
A. Vitamin B1
B. Vitamin B2
C. Vitamin B3
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D. Vitamin B5
E. Vitamin B6
Explanation:
The correct answer is A. Vitamin B1, or thiamine, is the
coenzyme required (as the pyrophosphate)
for the decarboxylation of alpha-ketoacids. An exampleof this reaction is pyruvate decarboxylase
reaction in alcoholic fermentation. Other reactions suchas that catalyzed by pyruvate dehydrogenase
also rely on thiamine pyrophosphate for decarboxylation,but require other cofactors as well.
Thiamine is also required for the generation of pentose
phosphates for nucleotide synthesis in thepentose phosphate pathway (hexose monophosphate
shunt), serving as a cofactor for transketolase.
Vitamin B2(choice B), or riboflavin, is a constituent ofFMN (flavin mononucleotide) and FAD (flavin
adenine dinucleotide). It functions in hydrogen and
electron transport.
Vitamin B3(choice C), or niacin (nicotinic acid), is a
coenzyme that is also involved in hydrogenand electron transport. Nicotinic acid functions in the
form of NAD and NADP.
Vitamin B5(choice D), or pantothenic acid, is conjugated
with coenzyme A to act as a carboxylic acid
carrier.
Vitamin B6(choice E), or pyridoxine, is required as a
cofactor for pyridoxal phosphate andpyridoxamine phosphate. Both of these cofactors are
essential to protein metabolism and energy
production.
A newborn presents with severe acidosis, vomiting,
hypotonia, and neurologic deficits. Serum analysisreveals elevated levels of lactate and alanine. These
observations suggest a deficiency in which of
the following enzymes?
A. Alanine aminotransferase
B. Glutamate dehydrogenase
C. Lactate dehydrogenase
D. Pyruvate carboxylase
E. Pyruvate dehydrogenase
Explanation:
The correct answer is E. Pyruvate dehydrogenase (PDH)
catalyzes the irreversible conversion ofpyruvate to acetyl-CoA. If PDH is absent, pyruvate will
be used in other pathways instead. Pyruvate
will be converted to alanine via alanine aminotransferase(choice A) and to lactate via lactate
dehydrogenase (choice C).
Glutamate dehydrogenase (choice B) is involved in
oxidative deamination, releasing ammonium ion for
urea synthesis. Deficiency of this enzyme would notcause the symptoms described.
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Pyruvate carboxylase (choice D) is a gluconeogenic
enzyme that catalyzes the conversion of pyruvate
to oxaloacetate. Deficiency of this enzyme would notcause the symptoms described.
The activity of which of the following enzymes is directly
affected by citrate?
A. Fructose-2,6-bisphosphatase
B. Isocitrate dehydrogenase
C. Phosphofructokinase I
D. Pyruvate carboxylase
E. 6-phosphogluconate dehydrogenase
Explanation:
The correct answer is C. Citrate is produced by citratesynthase from acetyl CoA and oxaloacetate.
This reaction takes place in the mitochondria, but citrate
can move freely from the mitochondria intothe cytosol. When the citric acid cycle slows down,
citrate accumulates. In the cytosol, it acts as a
negative allosteric regulator of phosphofructokinase I,the enzyme that catalyzes the committed step
of glycolysis.
Fructose-2,6-bisphosphatase (choice A) breaks down
fructose-2,6-bisphosphate, a potent allosteric
activator of phosphofructokinase I. Fructose-2,6-bisphosphatase is activated by cyclic
AMP-dependent
protein kinase.
Isocitrate dehydrogenase (choice B) converts isocitrate
to alpha-ketoglutarate in the citric acidcycle. It is allosterically stimulated by ADP and inhibited
by ATP and NADH. This reaction produces
NADH and CO2.
Pyruvate carboxylase (choice D) is a mitochondrial
enzyme that converts pyruvate to oxaloacetate. It
is important in gluconeogenesis and replenishes theoxaloacetate in the citric acid cycle.
6-phosphogluconate dehydrogenase (choice E) converts6-phosphogluconate to ribulose 5-phosphate in
the pentose phosphate shunt pathway.
Which of the following enzymes is stimulated byglucagon?
A. Acetyl-CoA carboxylase
B. Glycogen phosphorylase
C. Glycogen synthase
D. HMG-CoA reductase
E. Pyruvate kinase
Explanation:
The correct answer is B. Before you started analyzing all
of the answer choices you should havereminded yourself that glucagon increases serum
glucose. So an enzyme stimulated by glucagon might
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be involved in either the breakdown of glycogen to
glucose (glycogenolysis) or in the creation of
glucose from noncarbohydrate precursors(gluconeogenesis). Glycogen phosphorylase catalyzes
the
first step in glycogenolysis; it makes sense that it would
be stimulated by glucagon.
Acetyl-CoA carboxylase (choice A) catalyzes the first
step in fatty acid synthesis, an anabolicprocess that would be stimulated by insulin, not
glucagon.
As its name implies, glycogen synthase (choice C) isinvolved in the synthesis of glycogen. Glucagon
(and epinephrine) stimulate the phosphorylation and
inactivation of glycogen synthase.
HMG-CoA reductase (choice D) is the key enzyme
involved in the synthesis of cholesterol. Since this
is an anabolic process that occurs in the well-fed state,you would expect it to be stimulated by
insulin and inhibited by glucagon (which it is).
Pyruvate kinase (choice E) catalyzes the last reaction of
glycolysis. You would expect it to be
inhibited by glucagon (thus decreasing the amount ofglucose consumption). Glucagon promotes the
phosphorylation of pyruvate kinase, which renders it
inactive.
Which of the following inhibits the activity of acetyl-CoA
carboxylase?
A. Citrate
B. Glucagon
C. High-carbohydrate, low-fat diet
D. Insulin
Explanation:
The correct answer is B. The key thing to remember here
is that acetyl-CoA carboxylase catalyzes thefirst and rate-limiting step of fatty acid synthesis. If you
got that far, you could have figured
out which of the choices would inhibit the synthesis offatty acids. Certainly glucagon, a catabolic
hormone released in response to low blood glucose,
would be a likely candidate to inhibit the
synthesis of fatty acids. In fact, glucagon inhibits fattyacid synthesis by a cAMP-dependent
phosphorylation of acetyl-CoA carboxylase. Conversely,
glucagon stimulates fatty acid oxidation.
Citrate (choice A) is a key player in fatty acid synthesis(citrate shuttle). Therefore, the
presence of citrate would stimulate, not inhibit,acetyl-CoA carboxylase.
A high-carbohydrate, low-fat diet (choice C) wouldstimulate, not inhibit, the synthesis of fatty
acids.
In contrast to glucagon, insulin (choice D) is an anabolic
hormone that promotes fatty acid
synthesis and therefore would stimulate acetyl-CoAcarboxylase. It does so by dephosphorylating the
enzyme.
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An individual lacking the enzyme tyrosinase would be
particularly predisposed to develop which of thefollowing?
A. Glioblastoma multiforme
B. Hemangioblastoma
C. Hepatoma
D. Melanoma
E. Renal cell carcinoma
Explanation:
The correct answer is D. This question is simple if you
know that tyrosinase is an enzyme in the
biosynthetic pathway for melanin formation from
tyrosine. A lack of tyrosinase causes one form ofalbinism; a second form is caused by defective tyrosine
uptake. Patients with albinism are
vulnerable to developing cancers of the skin of all types,including basal cell carcinoma, squamous
cell carcinoma, and melanoma. The melanomas are
unusual in that they are non-pigmented (amelanotic)rather than black, since the patients cannot form
melanin.
A newborn baby has multiple hemorrhages. Clotting
studies demonstrate an elevated prothrombin time. An
abnormality of which of the following biochemicalprocesses is likely present in this patient?
A. Conversion of homocysteine to methionine
B. Conversion of methylmalonyl CoA to succinyl CoA
C. Degradation of cystathionine
D. Formation of gamma-carboxyglutamate residues
E. Hydroxylation of proline
Explanation:
The correct answer is D. Deficiency of vitamin K
produces a clotting disorder characterized by anelevated prothrombin time and easy bleeding,
particularly in neonates (hemorrhagic disease of the
newborn). The biochemical basis for this hemorrhagic
tendency is that glutamate residues on FactorsII (Thrombin), VII, IX, and X must be converted to
gamma-carboxyglutamate residues (in a vitamin K-
requiring reaction) for optimal activity.
The conversion of homocysteine to methionine (choiceA) requires vitamin B12.
Conversion of methylmalonyl CoA to succinyl CoA
(choice B) requires vitamin B12.
Degradation of cystathionine (choice C) requires vitamin
B6.
Hydroxylation of proline (choice E) requires vitamin C.
Vitamin C deficiency can cause easy bruising,
but will not prolong the prothrombin time.
A very ill infant is admitted to the hospital. Laboratory
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examination reveals a very high serum
concentration of lactic acid. In addition to taking steps
to correct the acidosis, the attendingphysician prescribes thiamine. The rationale for thiamine
administration is that thiamine is
converted to a coenzyme used by which of the following
enzymes?
A. Lactate dehydrogenase
B. Pyruvate carboxylase
C. Pyruvate dehydrogenase
D. Pyruvate kinase
E. Transketolase
Explanation:
The correct answer is C. Thiamine is a water-solublevitamin that is converted to the coenzyme
thiamine pyrophosphate. This coenzyme is used by
pyruvate dehydrogenase to convert pyruvate toacetyl coenzyme A. In the absence of thiamine, pyruvate
accumulates and can be converted by lactate
dehydrogenase to lactate, which is spilled in the bloodcausing lactic acidosis.
Lactate dehydrogenase (choice A) produces lactate frompyruvate but does not use thiamine
pyrophosphate.
Some lactic acidosis might be produced by decreased
pyruvate carboxylase activity (choice B), but
the enzyme requires biotin rather than thiaminepyrophosphate.
Pyruvate kinase (choice D) makes pyruvate fromphosphoenolpyruvate, but does not use thiamine
pyrophosphate.
Transketolase (choice E) requires thiamine
pyrophosphate, but operates in another pathway
(pentose
phosphate pathway). Decreased transketolase activity isnot associated with the development of
lactic acidosis.
A 69-year-old edentulous alcoholic male who lives alone
is admitted to the hospital for evaluation of a
shoulder wound that is not healing well. On physical
examination, numerous ecchymoses are noted onthe posterior aspect of his legs and thighs. Careful
examination of the man's skin reveals minute
hemorrhages around hair follicles and splinter
hemorrhages in the nail beds. Laboratory examination
is remarkable for a hemoglobin of 10 (normal 14-18g/dL); no other hematologic abnormalities are
noted. Therapy should consist of
A. administration of factor VIII
B. administration of iron
C. administration of vitamin B12
D. administration of vitamin C
E. administration of vitamin K
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Explanation:
The correct answer is D. The patient described suffersfrom scurvy, due to a deficiency of dietary
vitamin C. Absence of vitamin C leads to impaired
hydroxylation of proline residues in the nascent
procollagen chains, leading to weakness of blood vesselwalls. Clinically, the deficiency syndrome
is characterized by perifollicular hemorrhages,
fragmentation of hairs, purpura, ecchymoses,splinter hemorrhages, and hemorrhages into muscle. In
patients with normal dentition, gum changes(swelling, bleeding, loosening of teeth) are also noted.
Without supplementation with vitamin C,death may eventually occur.
Administration of factor VIII (choice A) would beindicated for factor VIII deficiency, which would
also lead to a prolonged PTT (partial thromboplastin
time), which was not noted.
Administration of iron (choice B) would be of benefit in
iron-deficiency anemia, but there is no
indication of a hypochromic, microcytic anemia in thispatient. The anemia of scurvy is typically
normochromic and normocytic, due to bleeding.
Administration of vitamin B12(choice C) would be
indicated for a megaloblastic anemia. Although a
macrocytic anemia may be observed in scurvy (due toconcomitant dietary folate deficiency or
perturbations in the folate pool), this patient did not
show macrocytosis.
Administration of vitamin K (choice E) would be
appropriate in the setting of vitamin K deficiency,which would produce prolongations of the prothrombin
time (PT), followed eventually by prolongation
of the PTT as the vitamin K-dependent factors (II, VII ,IX, X, protein C, and protein S) are
depleted.
A Guatemalan child with a history of meconium ileus is
brought in to a clinic because of a chronic
cough. The mother notes a history of respiratory tract
infections and bulky, foul-smelling stools.After assessment of the respiratory tract illness, the
practitioner should also look for signs of
A. cystinuria
B. hypoglycemia
C. iron deficiency anemia
D. sphingomyelin accumulation
E. vitamin A deficiency
Explanation:
The correct answer is E. The child is likely suffering from
cystic fibrosis. In this disorder, anabnormality of chloride channels causes all exocrine
secretions to be more viscous than normal.
Pancreatic secretion of digestive enzymes is oftenseverely impaired, with consequent steatorrhea
and deficiency of fat-soluble vitamins, including vitamin
A.
Cystinuria (choice A) is a relatively common disorder in
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which a defective transporter for dibasic
amino acids (cystine, ornithine, lysine, arginine; COLA)
leads to saturation of the urine withcystine, which is not very soluble in urine, and
precipitates out to form stones.
Hypoglycemia (choice B) is not a prominent feature ofchildren with cystic fibrosis who are on a
normal diet. Hyperglycemia may occur late in the course
of the disease.
Iron deficiency anemia (choice C) is not found with anyregularity in children with cystic fibrosis.
Sphingomyelin accumulation (choice D) is generally
associated with deficiency of sphingomyelinase,
as seen in Niemann-Pick disease.
In which of the following laboratory tests would you
expect to find the greatest disparity in reference
intervals between men and (non-pregnant) women?
A. Mean corpuscular volume
B. Serum alkaline phosphatase
C. Serum ferritin
D. Serum glucose
E. Serum sodium
Explanation:
The correct answer is C. Men have higher reference
intervals than women in tests related to iron andhemoglobin (Hb) concentration in blood. The normal
reference interval for Hb concentration in women
is lower (12.0-16.0 gm/dL) than that for men(13.5-17.5 gm/dL) due to lower serum testosterone
levels (testosterone is higher in men and stimulates
erythropoiesis) and blood loss during menses.Furthermore, women normally have about 400 mg of
iron (as ferritin) in their bone marrow iron stores
versus an average of 1000 mg of iron for men. In the
absence of inflammation, the small circulatingfraction of ferritin (choice C) correlates well with ferritin
stores in the bone marrow. Hence, men
have different reference intervals for serum ferritin thando women (15-200 ng/mL in men versus
12-150 ng/mL in women).
The mean corpuscular volume (choice A), serum alkalinephosphatase (choice B), serum glucose (choice
D), and serum sodium (choice E) are similar in both
sexes.
A competitive inhibitor of an enzyme will
A. alter the Vmax of the reaction
B. bind to the same site as the substrate
C. decrease the apparent Km for the substrate
D. decrease the turnover number
E. form an irreversible complex with the enzyme
Explanation:
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The correct answer is B. Substances that reduce the
activity of an enzyme are called inhibitors.
Reversible inhibitors bind to an enzyme but rapidlydissociate from it [in contrast to irreversible
inhibitors (choice E), which bind tightly and dissociate
very slowly from the enzyme]. There are
several types of reversible inhibitors:
Competitive inhibitors usually resemble the substrate
and compete with it for binding at the activesite (choice B). Thus, increasing the concentration of
substrate will decrease the percentinhibition of the enzyme. The Vmax is unchanged, but
the Km is increased.
A noncompetitive inhibitor binds with equal affinity to
both enzyme and enzyme-substrate complex.This binding leads to a distortion of the substrate
binding site, so new substrate cannot bind
and/or the product cannot be released. In this kind of
inhibition, the Vmax is decreased (choice A),but the Km is not altered. Adding more substrate will
not reverse this type of inhibition. This is
the equivalent of decreasing the turnover number(choice D).
An uncompetitive inhibitor does not bind to freeenzyme, but binds to the enzyme-substrate complex
at a site other than the catalytic site. Once bound by the
inhibitor, the enzyme is trapped in theenzyme-substrate complex state until the inhibitor
dissociates. In this kind of inhibition, the
slope of the reaction (which is the ratio Km/Vmax)remains the same, but both Vmax (choice A) and Km
(choice C) are reduced.
A 9-year-old child in a developing country is brought to
a clinic by his parents because he has trouble
keeping up with his classmates on the playground.Physical examination is remarkable for pulmonary
rales. Chest x-ray shows biventricular dilation of the
heart. Deficiency of which of the followingvitamins is the most likely cause of this child's condition
?
A. Ascorbic acid
B. Retinol
C. Riboflavin
D. Thiamine
E. Vitamin K
Explanation:
The correct answer is D. Thiamine deficiency is mostfrequently encountered in alcoholics and in
developing countries. Deficiency of this vitamin can takeseveral forms: dilated cardiomyopathy
(wet beriberi ), polyneuropathy (dry beriberi), and
mamillary bodydegeneration (Wernicke-Korsakoff syndrome).
Ascorbic acid (choice A, Vitamin C) deficiency causesscurvy, associated with capillary fragility,
bony abnormalities, and poor wound healing.
Retinol (choice B, Vitamin A) deficiency causes
blindness and impaired immune responses.
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Riboflavin ( choice C) deficiency causes cheilosis,
glossitis, and dermatitis.
Vitamin K (choice E) deficiency causes impaired blood
clotting because of decreased production offactors II, VII, IX , and X.
A 2-month-old child is evaluated for failure to thrive. As
the pediatrician is examining the child, aconvulsion occurs. Stat serum chemistries demonstrate
severe hypoglycemia, hyperlipidemia, lacticacidosis, and ketosis. Physical examination is remarkable
for hepatomegaly, a finding confirmed by CTscan, which also reveals renomegaly. Which of the
following diseases best accounts for this
presentation?
A. Gaucher's disease
B. McArdle's disease
C. Niemann-Pick disease
D. Pompe's disease
E. Von Gierke's disease
Explanation:
The correct answer is E. Von Gierke's disease is a
glycogen storage disease caused by a deficiency
of glucose-6-phosphatase. It typically presents withneonatal hypoglycemia, hyperlipidemia, lactic
acidosis, and ketosis. Failure to thrive is common in
early life; convulsions may occur due toprofound hypoglycemia. The glycogen accumulation in
von Gierke's disease occurs primarily in the
liver and kidneys, accounting for the enlargement ofthese organs. Gout may develop later because of
the derangement of glucose metabolism.
Even if you don't remember all of the details of the
presentation of these genetic diseases, you
should be able to narrow the choices:
Gaucher's disease (choice A) and Niemann-Pick disease
(choice C) are lipid storage diseases, and
would not be expected to produce hypoglycemia.
The other diseases are glycogen storage diseases, but
McArdle's (choice B) and Pompe's (choice D)
disease affect muscle rather than liver, and would not beexpected to produce profound hypoglycemia
since the liver is the major source for blood glucose.
An individual with megaloblastic anemia is found to
have a significant folate deficiency. Erythropoiesisis hampered in this man due to his inability to perform
which type of enzymatic reaction?
A. Acyl transfer
B. Carboxylation
C. Decarboxylation
D. Hydroxylation
E. Methylation
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Explanation:
The correct answer is E. Folic acid is a pteridine vitaminthat exists as tetrahydrofolate (TH4) in
its most reduced form. TH4 can accept methyl,
methylene, or formyl carbons and transfer them as
methyl groups. This function is vital in nucleotide andamino acid synthesis.
Pantothenic acid is a key vitamin in acyl transferreactions (choice A). It forms part of coenzyme
A, which transfers acyl groups in