03-14-2008, 01:07 PM
hey guys, will post more questions tonight, here is few more for your review....GL.
The parents of a 6-month-old child who was normal at birth bring her into the clinic. Since their emigration to the
U.S. from Eastern Europe soon after her birth, the child has developed diminished responsiveness, 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 caused by the
deficiency of hexosaminidase A, which leads to the accumulation of ganglioside GM2 in neurons, 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.
The incidence 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 produces Duchenne 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, destructive behavior.
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 tubular phosphate 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 immediately compromised 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 immediately important function for most cells. The
direct effect of this is the energy (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). This process requires considerable energy (1 ATP per
3Na+/2K+ exchange), since both the Na+ and K+ are traveling against a concentration gradient. This direct
effect of the Na+/ K+ ATPase may seem trivial, but the secondary consequences are dramatic. The Na+/ K+
ATPase helps establish the transmembrane potential of the cell (because the quantitatively uneven exchange
of Na+/ K+ drives 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 and transmembrane transport systems that allow entry into the cell of the
large variety of small molecules and ions that it needs. The first microscopically visible 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 any metabolic 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 leaves three possibilities:
fructokinase, fructose 1-phosphate aldolase, and galactose 1-P-uridyl transferases. Of these, only fructokinase
deficiency produces 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 14CO2 from 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
E. N10-Formyltetrahydrofolate
Explanation:
The correct answer is A. In the first step of pyrimidine synthesis, 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 of water, followed by oxidation to yield orotic acid. Addition of ribose-5-phosphate
produces orotidylic acid, which is decarboxylated by orotidylate decarboxylase to yield uridylic acid. The carbon
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 in purine
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 classic contraction band
necrosis of the myocardium. Biological specimens confirm the presence of cocaine and metabolites. Activity of
which of the following enzymes was 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 contraction band necrosis by blocking the reuptake of norepinephrine,
resulting in excessive vasoconstriction of coronary vessels, leading to ischemia and infarction of heart tissue.
Under these pathological conditions, 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 the rate-limiting enzyme of glycolysis, and its activity would therefore
be increased.
Phosphoenolpyruvate carboxykinase (choice A) is a regulatory enzyme in gluconeogenesis, which is induced by
cortisol, epinephrine, and glucagon. It functions in the hepatic synthesis of glucose when energy levels from
beta-oxidation of fatty acids are adequate.
Pyruvate dehydrogenase (choice C) produces acetyl-CoA from pyruvate and coenzyme A, bridging glycolysis
and the Krebs cycle. It requires 5 cofactors, 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 is also known as Complex II. The Krebs cycle only functions if
oxygen is in appropriate concentrations since it is regulated by the levels of NADH, which is only consumed by
the electron transport chain if there is enough oxygen. The absence of oxygen leads to an accumulation of
NADH and a subsequent decrease in the enzyme activities of the Krebs cycle.
Transketolase (choice E) is a thiamine requiring enzyme of 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. On questioning, the mother reported that she has noticed yellow-orange crystals in
his diapers, but has not mentioned them to anyone. A genetic defect in which 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 uric acid 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 of purines 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 leads to 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 of branched 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 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 a competitive
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 noncompetitive inhibition.
Note that in a Lineweaver-Burk plot, the slope is Km/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 the slope (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 of Km). 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 of effects, 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 pyruvate from glycolysis
(thereby increasing, rather than decreasing the lactate/pyruvate ratio; choice D).
A couple brings in their 6-month-old child because they are concerned about the child's inability to sit without
support. The physician interviews the parents and ascertains that they are both Ashkenazic Jews. The doctor
should inform them that, because of their 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 of these 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 with a normal life span and causes hepatosplenomegaly with CNS involvement. (The
infantile Type II and the juvenile Type III forms cause more serious disease but are not seen with increased
incidence in Ashkenazic Jews.) None of the other conditions listed occur with greater frequency in Ashkenazic
Jews. In this case, also note that many perfectly normal children cannot sit without support at 6 months of age,
so the child may well be healthy.
A 2-year-old retarded child is evaluated by a metabolic specialist. The child's history is significant for failure to
thrive and progressive neurologic deterioration, including deafness and blindness. Physical examination is
remarkable for hepatosplenomegaly, 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. Hepatosplenomegaly accompanied by progressive neurologic deterioration should
make you think of lipid storage diseases; Niemann-Pick disease is the only lipid storage disease in the answer
choices. Niemann-Pick disease is due to a deficiency of sphingomyelinase, leading to an accumulation of
sphingomyelin. It is most common among Ashkenazic Jews and generally results in death by age 2. The
cherry-red spot is also a 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 tyrosine metabolism that would not produce the listed symptoms.
von Gierke's disease (choice E) is a severe form of glycogen storage disease characterized by hypoglycemia,
hepatomegaly, and renomegaly.
The parents of a 6-month-old child who was normal at birth bring her into the clinic. Since their emigration to the
U.S. from Eastern Europe soon after her birth, the child has developed diminished responsiveness, 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 caused by the
deficiency of hexosaminidase A, which leads to the accumulation of ganglioside GM2 in neurons, 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.
The incidence 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 produces Duchenne 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, destructive behavior.
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 tubular phosphate 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 immediately compromised 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 immediately important function for most cells. The
direct effect of this is the energy (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). This process requires considerable energy (1 ATP per
3Na+/2K+ exchange), since both the Na+ and K+ are traveling against a concentration gradient. This direct
effect of the Na+/ K+ ATPase may seem trivial, but the secondary consequences are dramatic. The Na+/ K+
ATPase helps establish the transmembrane potential of the cell (because the quantitatively uneven exchange
of Na+/ K+ drives 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 and transmembrane transport systems that allow entry into the cell of the
large variety of small molecules and ions that it needs. The first microscopically visible 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 any metabolic 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 leaves three possibilities:
fructokinase, fructose 1-phosphate aldolase, and galactose 1-P-uridyl transferases. Of these, only fructokinase
deficiency produces 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 14CO2 from 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
E. N10-Formyltetrahydrofolate
Explanation:
The correct answer is A. In the first step of pyrimidine synthesis, 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 of water, followed by oxidation to yield orotic acid. Addition of ribose-5-phosphate
produces orotidylic acid, which is decarboxylated by orotidylate decarboxylase to yield uridylic acid. The carbon
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 in purine
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 classic contraction band
necrosis of the myocardium. Biological specimens confirm the presence of cocaine and metabolites. Activity of
which of the following enzymes was 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 contraction band necrosis by blocking the reuptake of norepinephrine,
resulting in excessive vasoconstriction of coronary vessels, leading to ischemia and infarction of heart tissue.
Under these pathological conditions, 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 the rate-limiting enzyme of glycolysis, and its activity would therefore
be increased.
Phosphoenolpyruvate carboxykinase (choice A) is a regulatory enzyme in gluconeogenesis, which is induced by
cortisol, epinephrine, and glucagon. It functions in the hepatic synthesis of glucose when energy levels from
beta-oxidation of fatty acids are adequate.
Pyruvate dehydrogenase (choice C) produces acetyl-CoA from pyruvate and coenzyme A, bridging glycolysis
and the Krebs cycle. It requires 5 cofactors, 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 is also known as Complex II. The Krebs cycle only functions if
oxygen is in appropriate concentrations since it is regulated by the levels of NADH, which is only consumed by
the electron transport chain if there is enough oxygen. The absence of oxygen leads to an accumulation of
NADH and a subsequent decrease in the enzyme activities of the Krebs cycle.
Transketolase (choice E) is a thiamine requiring enzyme of 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. On questioning, the mother reported that she has noticed yellow-orange crystals in
his diapers, but has not mentioned them to anyone. A genetic defect in which 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 uric acid 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 of purines 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 leads to 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 of branched 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 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 a competitive
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 noncompetitive inhibition.
Note that in a Lineweaver-Burk plot, the slope is Km/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 the slope (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 of Km). 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 of effects, 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 pyruvate from glycolysis
(thereby increasing, rather than decreasing the lactate/pyruvate ratio; choice D).
A couple brings in their 6-month-old child because they are concerned about the child's inability to sit without
support. The physician interviews the parents and ascertains that they are both Ashkenazic Jews. The doctor
should inform them that, because of their 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 of these 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 with a normal life span and causes hepatosplenomegaly with CNS involvement. (The
infantile Type II and the juvenile Type III forms cause more serious disease but are not seen with increased
incidence in Ashkenazic Jews.) None of the other conditions listed occur with greater frequency in Ashkenazic
Jews. In this case, also note that many perfectly normal children cannot sit without support at 6 months of age,
so the child may well be healthy.
A 2-year-old retarded child is evaluated by a metabolic specialist. The child's history is significant for failure to
thrive and progressive neurologic deterioration, including deafness and blindness. Physical examination is
remarkable for hepatosplenomegaly, 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. Hepatosplenomegaly accompanied by progressive neurologic deterioration should
make you think of lipid storage diseases; Niemann-Pick disease is the only lipid storage disease in the answer
choices. Niemann-Pick disease is due to a deficiency of sphingomyelinase, leading to an accumulation of
sphingomyelin. It is most common among Ashkenazic Jews and generally results in death by age 2. The
cherry-red spot is also a 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 tyrosine metabolism that would not produce the listed symptoms.
von Gierke's disease (choice E) is a severe form of glycogen storage disease characterized by hypoglycemia,
hepatomegaly, and renomegaly.
