Kaplan Biochem Flashcards
1. Which of the following is the 3-carbon end-product of fatty acid metabolism? A. Acetoacetate B. Acetone C. ß-Hydroxybutyrate D. Diacylglycerol E. Monoacylglycerol
The correct answer is choice B. The theme of this question is lipid metabolism. Ketone bodies
[acetoacetate (choice A), acetone (choice B), and ß-hydroxybutyrate (choice C)] are lipid
breakdown products. The levels of these molecules can increase in poorly controlled diabetes mellitus
or starvation. Acetone is the 3-carbon fragment of this group.
Monoacylglycerols (choice E) and diacylglycerols (choice D) are neutral fats made from glycerol with
one or two fatty acids esterified to the glycerol, respectively.
- Folate plays a role in single-carbon unit transfer in the synthesis of nucleotides. Which of
the following nucleotides require folate for synthesis?
A. Adenosine, cytosine, and uracil
B. Adenosine, guanine, and thymidine
C. Adenosine, guanine, and uracil
D. Cytosine, thymidine, and uracil
E. Guanine, thymidine, and uracil
The correct answer is choice B. Folate is involved in the transfer of carbons 2 and 8 of the purine
nucleus (affecting adenosine and guanosine) and the 5-methyl group of thymidine. This means that
folate is required for synthesis of 3 of the 4 nucleic acid bases of DNA and 2 of the 4 nucleic acid
bases in RNA. It is thus no wonder that folate deficiency affects so many tissues with high mitotic rate.
Megaloblastic changes analogous to those seen in erythrocytes and their precursors can also be seen
in other cells produced by bone marrow (neutrophil, eosinophil, basophil, and macrophage and
megakaryocyte lines) and in epithelia throughout the body, including skin, mucous membranes such
as the mouth and vagina (where the changes can be seen on pap smear), stomach, intestinal linings,
and cells from lung or liver. Similar megaloblastic changes are observed throughout the body when
cobalamin (vitamin B12 ) deficiency is present, since cobalamin plays a role in methionine synthesis,
which is the source of the one-carbon unit “active-formate.” Cobalamin is also invovled in the
conversion of methylmalonic acid to succinic acid and is required to maintain the integrity of nerve
cells via an unknown biochemical pathway.
3. A patient is taking hormone supplements. The hormone binds to a receptor in the cell membrane, which activates tyrosine kinase activity. Which of the following hormones is this patient taking? A. Calcitrol B. Thyroxine C. Retinoic acid D. Insulin E. Protein synthesis
The correct answer is D.Insulin, a water-soluble hormone, binds to receptors in the cell membrane.
Receptor tyrosine kinase is activated, leading to protein phosphorylation. Tyrosine kinase receptors
are also involved in signaling by growth factors like PDGF (platelet derived growth factors) and EGF
(epidermal growth factor). Choice A, B and C - are all lipid soluble harmones, which diffuse through
the cell membrane, and bind to their respective receptors inside the cell. The hormone-receptor
complex then binds to hormone receptor elements in DNA, which then results in the observed
hormone effect.
- A 5-year-old child has blue-tinged sclera, hearing loss, and small, slightly blue, misshapen
teeth. Radiologic studies confirm the presence of numerous fractures of various ages. No
significant degree of bruising is seen over sites of recent fracture. The disease this child most
likely has is related to abnormal metabolism involving which of the following substances?
A. Collagen
B. Glycogen
C. Mucopolysaccharides
D. Purines
E. Tyrosine
The correct answer is A. The suspected disease is osteogenesis imperfecta, which is a rare genetic
disorder that occurs in both recessive and dominant forms. The clinical presentation, depending on
the specific form, varies from death in utero, to that described in the question stem, to very mild
disease with only a modest increase in bone fragility. Spontaneous fractures occur in utero or during
childhood. The different types all have defects in the synthesis of type I collagen, often with
insufficient or abnormal pro-1(1) or pro-2(1) chains. These deficits produce an unstable collagen triple
helix that is not as strong as normal collagen. Less severe mutations on type I collagen genes are
common, resulting in collagen disarray and predisposing to hypogonadal or idiopathic osteoporosis.
Defective glycogen (choice B) metabolism is associated with the various glycogen storage diseases,
such as von Gierke disease and Pompe disease. These diseases tend to present with profound
hypoglycemia, hepatomegaly, or muscle weakness.
Defective mucopolysaccharide (choice C) metabolism is associated with the mucopolysaccharidoses,
such as Hurler and Hunter syndromes. These diseases tend to present with abnormal facies
(“gargoylism”), deformed (“gibbus”) back, claw hand, and stiff joints.
Abnormalities of purine metabolism (choice D) are present in gout, which presents with joint
inflammation and often involves the great toe. The net result is due to chronic hyperuricemia.
Abnormalities of tyrosine metabolism (choice E) are associated with phenylketonuria (pale hair and
skin, mental retardation, musty smelling urine), albinism (pale hair, skin, increased skin cancer),
cretinism (decreased T3 and T4), tyrosinosis (liver and kidney disease), and alkaptonuria (chronic
arthritis and urine that turns black upon standing).
- An IgG2 molecule is composed of which of the following?
A. One alpha, one gamma2, and two kappa chains
B. One gamma1 chain and two kappa chains
C. Two gamma1 chains and one kappa and one lambda chain
D. Two gamma1 chains and two kappa chains
E. Two gamma2 chains and two kappa chains
The correct answer is E. IgG molecules contain two gamma heavy chains of a given subtype and two light chains (either kappa or lambda). The 2 in IgG2 indicates the subclass to which the molecule belongs. IgG2 contains two gamma2 chains (since a given B cell can only form one type of heavy 2 chain). The IgG molecule will contain either two kappa chains or two lambda chains, but never one of each (choice C). The standard serum concentration is 12 mg/mL. A given cell produces immunoglobulin molecules with a single type of heavy chain (compare with choice A). IgG molecules with gamma1 chains (choices B, C, and D) would be of the IgG1 subclass.
6. What is the lipase enzyme that degrades stored triacylglycerols in adipocytes? A. Gastric lipase B. Pancreatic lipase C. Lipoprotein lipase D. Hormone-sensitive lipase
The correct answer is D.Hormone-sensitive lipase is found in and degrades stored triacylglcerols in
adipocytes.
Gastric lipase (choice A) originates in the stomach, where it degrades dietary triacylglycerols.
Pancreatic lipase (choice B) is found in pancreas and degrades dietary triacylglycerols in the small
intestine.
Lipoprotein lipase (choice C) is found in extrahepatic tissues and acts on surface endothelial-cell
lining. The capillaries degrade triacylglycerols circulating in chylomicrons or VLDL.
- A 50-year-old man presents with headache, nausea, memory loss, abdominal pain, dark
colored lines in gums, neuropathy, and anemia. Which of the following enzyme/s is/are
inhibited in this patient?
A. ALA dehydrase and ferrochelatase
B. ALA synthase
C. Uroporphyrinogen I synthase
D. UDP-glucuronyl transferase
The correct answer is A. This is a case of lead poisoning. Lead inhibits ALA dehydrase and
ferrochelatase, the enzymes of the heme synthesis pathway. Other signs and symptoms include
coarse basophilic stippling of erythrocytes, lead deposits in abdomen, a gingiva, and epiphysis of
bone.
Choice B - ALA synthase is the rate-limiting enzyme of heme synthesis and is repressed by heme.
Choice C - is the enzyme of heme synthesis; its absence leads to acute intermittent porphyria.
Choice D - UDP-glucuronyl transferase is the enzyme of heme degradation, and is involved in the
formation of the conjugated form of bilirubin.
- 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
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).
Alcoholism is a syndrome consisting of two phases: problem drinking and alcohol addiction. Alcohol
addiction is defined as a physiologic dependence as manifested by evidence of withdrawal when
intake is interrupted. As a side note, thiamine is commonly deficient in chronic alcoholics. Remember,
thiamine is a necessary ketolase enzyme cofactor.
9. A young adult with albinism is found to be at increased risk for skin cancer. Which of the following is the precursor of melanin? A. Tryptophan B. Tyrosine C. Arginine D. Glycine
The correct answer is choice B. Albinism is caused by congenital deficiency of tyrosinase. It results
in an inability to synthesize melanin from tyrosine. Other derivatives of tyrosine are thyroxine,
dopamine, norepinephrine, and epinephrine.
Choice A - derivatives of tryptophan are niacin, serotonin, and melatonin.
Choice C - derivatives of arginine are creatine and urea.
Choice D - porphyrin is derived from glycine and eventually from heme.
10. A chronic alcoholic develops severe memory loss with marked confabulation. Deficiency of which of the following vitamins would be most likely to contribute to the neurologic damage underlying these symptoms? A. Folic acid B. Niacin C. Riboflavin D. Thiamine E. Vitamin B12
The correct answer is D.Wernicke-Korsakoff syndrome refers to the constellation of neurologic
symptoms 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. Wernicke’s
encephalopathy consists of the of confusion, ataxia and ophthalmoplegia. Anatomical damage to the
mamillary bodies and periventricular structures has been postulated as the cause. In the U.S., severe
thiamine deficiency is seen most commonly in chronic alcoholics. Thiamine deficiency can also
damage peripheral nerves (“dry” beriberi) and the heart (“wet” beriberi).
Folic acid deficiency (choice A) produces megaloblastic anemia 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.
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Vitamin B12 deficiency (choice E) produces megaloblastic anemia accompanied by degeneration of
the posterolateral spinal cord. This megaloblastic anemia is commonly known as pernicious anemia.
- One of the enzymes of the citric acid cycle, which is on the inner mitochondria membrane,
also functions as complex II of the electron transport chain. This enzyme is also responsible
for converting succinate to fumarate, producing FADH2. The enzyme is
A. isocitrate dehydrogenase
B. a ketoglutarate dehydrogenase
C. succinate dehydrogenase
D. succinyl CoA synthase
The correct answer is choice C. All Krebs cycle components are in the matrix of the mitochondria
except succinate dehydrogenase, which is in the inner mitochondrial membrane. Succinate
dehydrogenase reoxidizes FADH2 and passes electrons directly to Coenzyme Q.
Choice A - Isocitrate dehydrogenase, the rate limiting enzyme of citric acid cycle, produces NADH. It
is activated by ADP and inhibited by NADH.
Choice B - a ketoglutarate dehydrogenase, like pyruvate dehydrogenase, requires thiamine, lipoic
acid, CoA, FAD, NAD, and produces NADH.
Choice D - Succinyl CoA synthase catalyses a substrate level phosphorylation of GDP to GTP.
12. The extremely potent vasodilator nitric oxide (NO) is produced naturally by the body from which of the following amino acids? A. Arginine B. Aspartate C. Glutamate D. Methionine E. Proline
The correct answer is A. In the body, the very short acting (5-second half-life) signaling molecule
nitric oxide (NO) is synthesized by nitric oxide synthase (NOS). This enzyme is found in many tissues
and converts arginine to citrulline and NO. The vasodilation produced by NO normally occurs in
response to appropriate local biologic triggers, such as infection. However, this process may also
produce pathology if uncontrolled, since it is thought that the endotoxic shock that can complicate
bacterial septicemia may be related to continued activity of NOS. NO also plays a role in macrophage
activity, where its metabolites are toxic to ingested microorganisms.
Aspartate (choice B) is associated with donation of one of the nitrogens in urea, with the liver enzyme
aspartate aminotransferase (AST), and with nucleotide synthesis.
Glutamate (choice C) is associated with amino acid transport into the cell via the gamma-glutamyl
cycle, and with the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase
(ALT).
Methionine (choice D) is associated with 1-carbon transfer reactions.
Proline (choice E) is associated with the collagen helix.
13. Which of the following amino acids would most likely be found on the surface of a protein molecule? A. Alanine B. Arginine C. Isoleucine D. Leucine E. Phenylalanine
The correct answer is choice B. This question requires two logical steps. First, you need to
appreciate that hydrophilic amino acids are more likely to appear on the surface of a protein molecule,
whereas hydrophobic amino acids are most likely be found in the interior. Next, you need to figure out
which of the amino acids listed is hydrophilic. If you recall 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 the other choices have neutral side chains and are uncharged at physiologic pH. They would most
likely be found in the hydrophobic core of the protein structure. Alanine (choice A), isoleucine (choice
C), and leucine (choice D) all have aliphatic side chains; phenylalanine (choice E) and tryptophan
have aromatic side chains.
14. Dietary intake of which of the following amino acids can substitute for a portion of the daily requirement of niacin? A. Alanine B. Asparagine C. Methionine D. Proline E. Tryptophan
The correct answer is E. Tryptophan is an aromatic amino acid that contains an indole group. By a
complex series of minor enzymatic reactions, a small amount (~2%) of the tryptophan can be
converted to quinolinate, which can then be used in place of niacin (nicotinic acid) in NAD
(nicotinamide adenine dinucleotide) synthesis. Very high tryptophan levels can replace a portion of
the dietary requirements for niacin. The nutritional disease pellegra (characterized by swollen tongue,
dermatitis, neurologic dysfunction, and gastrointestinal dysfunction) usually occurs in the setting of
combined tryptophan and niacin deficiency.
Alanine (choice A), the amino acid with a methyl R group, is a substrate of the liver enzyme alanine
amino transferase (ALT, formerly called SGPT). Asparagine (choice B) is one of the sources of
ammonia for the urea cycle. Methionine (choice C) is a sulfur-containing amino acid that is
associated with methyl group transfer. Proline (choice D) is technically an imino acid, rather than an
amino acid, with a ring structure. You should remember that collagen has a high proline
concentration.
- A child is noted to be severely retarded. Physical examination reveals a pot-bellied, pale
child with a puffy face. The child’s tongue is enlarged. Dietary deficiency of which of the
following substances can produce this pattern?
A. Calcium
B. Iodine
C. Iron
D. Magnesium
E. Selenium
The correct answer is choice B. The disease is cretinism, characterized by a profound lack of thyroid hormone in a developing child, leading to mental retardation and the physical findings described in the question stem. Cretinism can be due to dietary deficiency of iodine (now rare in this country because of iodized salt), to developmental failure of thyroid formation, or to a defect in thyroxine synthesis. Iodine in the diet is absorbed at the digestive tract as iodide (I-). The follicle cells in the thyroid gland absorb 120-150 μg of iodide ions per day. Iodide ions are actively transported into the thyroid follicle cells. The active transport mechanism for iodide is stimulated by TSH. Calcium deficiency (choice A) in children can cause osteoporosis 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 the parathyroid response to hypocalcemia. Selenium deficiency (choice E) is rare, but may cause a reversible form of cardiomyopathy.
- A chronically malnourished patient notices her “hair falling out.” She is on a strict fat-free
diet. She probably has a deficiency in which vitamins?
A. Vitamin A
B. Vitamin C
C. Vitamin D
D. Vitamin E
E. Vitamin K
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 deficiency is one of the most common deficiencies in developing countries. Vitamin A is necessary for formation of retinal pigments (deficiency can cause night blindness) and for appropriate differentiation of epithelial tissues (including hair follicles, mucous membranes, skin, bone, and adrenal cortex). Vitamin C (choice B), which is water soluble rather than oil soluble, is necessary for collagen synthesis. Deficiency is associated with development of scurvy. Vitamin D (choice C) is important in calcium absorption and metabolism. Calcium and phosphate irregularities can occur in deficiencies. Vitamin E (choice D) is a lipid antioxidant that is important in the stabilization of cell membranes. Vitamin K (choice E) is necessary for normal blood coagulation. When vitamin K is deficient, clotting factors 2, 7, 9, and 10 will be decreased leading to an increased pT/INR.
17. Which of the following amino acids is most responsible for the buffering capacity of hemoglobin and other proteins? A. Arginine B. Aspartic acid C. Glutamic acid D. Histidine E. Lysine
The correct answer is D.Histidine, lysine and arginine are amino acids with basic side chains.
Remember that a buffer is most effective when its pKa is within the pH range of the surrounding
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medium. Histidine is the only amino acid with good buffering capacity at physiologic pH. The
imidazole side chain of histidine has a pKa around 6.5 and can reversibly donate and accept protons
at physiologic pH.
Arginine (choice A) and lysine (choice E) are basic amino acids with pKa’s of 12.5 and 10.5,
respectively; at physiologic pH both will behave as bases and accept protons.
Aspartic acid (choice B) and glutamic acid (choice C) are acidic amino acids with pKa’s of
approximately 4; at physiologic pH they will behave as acids and donate protons. Their side chains
are almost always negatively charged.
18. Which of the following cofactors is required for decarboxylation of alpha-ketoacids? A. Vitamin B1 B. Vitamin B2 C. Vitamin B3 D. Vitamin B5 E. Vitamin B6
The correct answer is A. Vitamin B1, or thiamine, is the coenzyme required (as the pyrophosphate)
for the decarboxylation of alpha-ketoacids. An example of this reaction is pyruvate decarboxylase
reaction in alcoholic fermentation. Other reactions such as 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 the pentose
phosphate pathway (hexose monophosphate shunt), serving as a cofactor for transketolase. The
primary cause of thiamine deficiency in the US is due to alcoholism. Thiamine deficiency is known as
beri beri. As this condition progresses, Wernicke-Korsakoff syndrome, which is seen in chronic
alcoholics, can develop.
Vitamin B2 (choice B), or riboflavin, is a constituent of FMN (flavin mononucleotide) and FAD (flavin
adenine dinucleotide). It functions in hydrogen and electron transport. Deficiency is associated with
the development of cheilosis, angular stomatitis and glossitis.
Vitamin B3 (choice C), or niacin (nicotinic acid), is a coenzyme that is also involved in hydrogen and
electron transport. Nicotinic acid functions in the form of NAD and NADP. Niacin is used clinically for
the treatment of hypercholesteremia and hypertriglyceredemia.
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 and
pyridoxamine phosphate. Both of these cofactors are essential to protein metabolism and energy
production. Deficiencies can lead to the development of mouth soreness, glossitis, cheilosis,
weakness and irritability. Severe deficiency can cause peripheral neuropathy and anemia.
19. A stretch of 25 hydrophilic amino acids in a protein could be found in a A. signal sequence B. start transfer sequence C. stop transfer sequence D. transmembrane domain E. triple helix
The correct answer is E. A triple helix, such as the one found in collagen, is composed of three
polypeptide chains wound together to form one structure. The chains are highly enriched with the
hydrophilic amino acids glycine and proline.
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A signal sequence (choice A) contains a stretch of 30 hydrophobic amino acids.
The start transfer sequence (choice B) and stop transfer sequence (choice C) are each composed of
25-30 hydrophobic amino acids.
Transmembrane domains (choice D) contain 25-30 hydrophobic amino acids. This is enough to form
an alpha helix that will span a lipid bilayer.
20. The process involved in formation of protein from RNA is A. Replication B. Translation C. Transcription D. Transformation
The correct answer is choice B.In translation, protein synthesis occurs by peptide bond formation
between successive amino acids, whose order is specified by a gene and thus by an mRNA
Choice A - Replicationis a process in which two daughter DNA molecule are produced, that are each
identical to the parental DNA molecule
Choice C - Transcription is a process in which mRNA is synthesized using DNA as template.
Choice D - Transformation is not involved in protein synthesis either from DNA or RNA
Putting the processes together:
- Folate plays a role in single-carbon unit transfer in the synthesis of nucleotides. Which of
the following nucleotides require folate for synthesis?
A. Adenosine, cytosine, and uracil
B. Adenosine, guanine, and thymidine
C. Adenosine, guanine, and uracil
D. Cytosine, thymidine, and uracil
E. Guanine, thymidine, and uracil
The correct answer is choice B. In summary, a nucleoside consists of a purine or pyrimidine base
linked to a pentose, and a nucleotide is a phosphate ester of a nucleoside. For example, adenine is
the base of the ribonucleoside adenosine and the ribonucleotide adenylate (AMP). Folate is involved
in the transfer of carbons 2 and 8 of the purine nucleus (affecting adenosine and guanosine) and the
5-methyl group of thymidine. This means that folate is required for synthesis of 3 of the 4 nucleic acid
bases of DNA and 2 of the 4 nucleic acid bases in RNA. It is thus no wonder that folate deficiency has
effects on so many tissues with high mitotic rate. Megaloblastic changes analogous to those seen in
erythrocytes and their precursors can also be seen in other cells produced by bone marrow
(neutrophil, eosinophil, basophil, and macrophage as well as megakaryocyte lines) and in epithelia
throughout the body, including skin, mucous membranes such as the mouth and vagina (where the
changes can be seen on Pap smear), stomach and intestinal linings, and cells from lung or liver.
Similar megaloblastic changes are observed throughout the body when cobalamin (vitamin B12)
deficiency is present, since cobalamin plays a role in methionine synthesis, which is the source of the
one-carbon unit “active-formate.” Cobalamin is also involved in the conversion of methylmalonic acid
to succinic acid and is required to maintain the integrity of nerve cells via an unknown biochemical
pathway.
- A 45-year-old mother has a 5-year-old daughter with a history of repeated respiratory
infections. The child has mental retardation, short stature, hypotonia with depressed nasal
bridge, upslanting palpebral fissure, and epicanthal fold. She is also at an increased risk for
leukemia. What is the probable chromosome abnormality?
A. Trisomy 13
B. Trisomy 18
C. Trisomy 21
D. Turner syndrome (45,X)
The correct answer is C. Trisomy 21 is the most common autosomal trisomy, and it causes Down syndrome. The increased risk of Down syndrome with increased maternal age is well documented. Trisomy 13 (choice A) features include oral facial clefts, microophthalmia, polydactyly, and renal defects. They usually do not survive to 1 year. Trisomy 18 (choice B) features include small mouth and ears, congenital heart defects, and overlapping fingers. Ninety percent die during the first year of life. Turner syndrome (choice D) features include reduced stature, webbed neck, and lymphedema of the wrists and ankles.
- The biochemical structure of all the hormones secreted by the anterior pituitary, posterior
pituitary, and pancreas can best be described as which of the following?
A. Amino acid derivatives
B. Catecholamines
C. Glucocorticoids
D. Peptides
E. Steroid hormones
The correct answer is D.In the human body there are three basic types of hormones: peptides
(protein derivatives), amino acid derivatives, and steroid hormones. Some examples of peptide
hormones are those produced in the anterior pituitary (growth hormone, adrenocorticotropin, thyroid
stimulating hormone, luteinizing hormone, and prolactin), the posterior pituitary (vasopressin and
oxytocin), and the pancreas (insulin and glucagon).
Amino acid derivatives (choice A) include tyrosine and triiodothyronine, as well as the
catecholamines (choice B) dopamine, epinephrine, and norepinephrine.
Glucocorticoid hormones (choice C; e.g., cortisol) are a specific type of steroid hormone produced by
the adrenal cortex.
Steroid hormones (choice E) include the hormones produced in the adrenal cortex (cortisol and
aldosterone), the ovaries (estrogen and progesterone), the testes (testosterone), and the placenta
(estrogen and progesterone).
24. Which of the following enzymes is stimulated by glucagon? A. Acetyl-CoA carboxylase B. Glycogen phosphorylase C. Glycogen synthase D. HMG-CoA reductase E. Pyruvate kinase
The correct answer is choice B. Before you started analyzing all of the answer choices you should
have reminded yourself that glucagon increases serum glucose. So an enzyme stimulated by
glucagon might 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.
Clinical correlate: patients with Type I diabetes lose their response to hypoglycemia (but not to amino
acids in protein containing meals) within a year or so after developing diabetes. Type I diabetics rely
on the sympathetic nervous system to counter regulate hypoglycemia.
Acetyl-CoA carboxylase (choice A) catalyzes the first step in fatty acid synthesis, an anabolic process
that would be stimulated by insulin, not glucagon.
As its name implies, glycogen synthase (choice C) is involved in the synthesis of glycogen. Glucagon
(and epinephrine) stimulates 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 of glucose consumption). Glucagon promotes the
phosphorylation of pyruvate kinase, which renders it inactive.
25. The majority of ATP generated during a 100 meter race is derived from which of the following? A. ATP stores B. Creatine phosphate C. Gluconeogenesis D. Glycolysis E. Lipolysis
The correct answer is D.The key to this question is understanding how and when the body utilizes
fuel stores. The stores of ATP (choice A) will be used up in less than 1 second once the race has
started. Creatine phosphate (choice B) will be the primary source of energy for the next 3 or 4
seconds. After the creatine phosphate stores are depleted, the majority of ATP needed to complete
the race will be derived from glycolysis (anaerobic respiration). If the race were to last for an extended
period of time, then the processes of gluconeogenesis (choice C) and lipolysis (choice E) might be
utilized. Gluconeogenesis is the process of synthesizing glucose in the liver from non-carbohydrate
sources, such as amino and fatty acids. Lipolysis is the splitting up or decomposition of fat in the
body.
- As cells in the erythrocytic lineage mature and lose their nuclei, mitochondria, and
ribosomes, which of the following pathways can still be used to produce ATP?
A. Citric acid cycle
B. Electron transport chain
C. Glycolysis
D. Malate shuttle
E. Urea cycle
The correct answer is C. Circulating erythrocytes have a life span of about 60 days and are
dependent on a functioning Na+/K+ ATPase in the plasma membrane. This pump provides the
electrochemical force across the plasma membrane that helps to maintain the volume of the red cell
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at a constant level by regulating salt, and consequently water, flow into and out of the cell. When the
pump stops, the erythrocytes tend to lyse. It is therefore of extreme importance to the erythrocyte to
supply the ATP necessary to keep the pump running. This is accomplished through the use of
glycolysis, which converts glucose to pyruvate, with a net production of 2 ATP per glucose molecule.
The Krebs, or citric acid, cycle (choice A) is the central metabolic degradative pathway of aerobic
cells. However, it is located in mitochondria and requires the electron transport chain, making it
unavailable for mature red cells to use.
The electron transport chain (choice B) is located on the mitochondrial cristae and helps to convert
the energy of NADH and FADH2 to ATP.
The malate shuttle (choice D) is used to transport cytoplasmic NADH electrons into mitochondria and
is not available to erythrocytes.
The urea cycle (choice E) is used by liver cells for processing nitrogenous wastes, not generating
energy.
27. Megaloblastic anemia with folate deficiency is linked to an inability to perform which type of enzymatic process? A. Acyl transfer B. Carboxylation C. Decarboxylation D. Hydroxylation E. Methylation
The correct answer is E. Folic acid is a pteridine vitamin that 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 and amino acid synthesis.
Pantothenic acid is a key vitamin in acyl transfer reactions (choice A). It forms part of coenzyme A,
which transfers acyl groups in thiol esters as acetyl-CoA, succinyl-CoA, and other acyl-CoA forms.
Important vitamins in carboxylation reactions (choice B) include biotin and vitamin K. Biotin carries
the carboxyl group in the pyruvate carboxylase and acetyl-CoA carboxylase reactions. Vitamin K is
used in post-translational carboxylation of amino acid residues in blood clotting factors.
Oxidative decarboxylation reactions (choice C) require thiamine (vitamin B1). Examples include the
pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes.
Ascorbic acid (vitamin C) is a coenzyme in the hydroxylation (choice D) of lysyl and prolyl residues
for collagen synthesis.
28. Long term broad spectrum antibiotics with reduced clotting time in localized areas is an indication of a deficiency in what? A. Vitamin C B. Vitamin K C. Cyanocobalamine (B12) D. Thiamine (B1)
The correct answer is choice B. Prolonged treatment with broad-spectrum antibiotics eliminates
intestinal bacteria that supply vitamin K. Vitamin K catalyses gamma carboxylation of glutamic acid
residues on various proteins concerned with blood clotting. Deficiency is characterized by prolonged
PT but normal bleeding time.
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Choice A - Vitamin C deficiency leads to scurvy with increased bleeding time but normal PT. A diet
deficient in vitamin C results in scurvy.
Choice C - Vitamin B12 deficiency is usually caused by malabsorption and results in megaloblastic
anemia and progressive peripheral neuropathy.
Choice D - The most common cause of thiamine deficiency is alcoholism. Because alcohol interferes
with absorption, deficiency results in dry and wet beri-beri.
- The finding that almost all of the melanoma cells have very large, visible nucleoli suggests
that these cells are making large amounts of which of the following?
A. Cell surface markers
B. Golgi apparatus
C. Immunoglobulins
D. New DNA
E. Ribosomes
The correct answer is E. The nucleolus is the site of manufacture of ribosomal RNA with its
subsequent packaging into ribosomes. Consequently, very large nucleoli indicate an increased rate of
ribsome production, which, in turn, suggests an increased rate of production of proteins. Large
nucleoli are seen in many active cancers but can also be prominent in benign conditions
characterized by high metabolic rate, such as tissue repair after trauma.
Depending on the cells involved, the increased protein production associated with more ribosomes
might produce more cell surface markers (choice A), but it is impossible to predict this simply from
the presence of a large nucleolus.
You should associate a large Golgi apparatus (choice B) with transport of material to the cell surface.
Plasma cells that produce large amounts of immunoglobulins (choice C) may have large nucleoli, but
more specifically have a very large endoplasmic reticulum and Golgi apparatus.
The nucleolus is not involved with new DNA (choice D) synthesis; this is done elsewhere in the
nucleus.
30. Which type of enzyme reaction is effected by a folic acid deficiency? A. Acyl transfer B. Carboxylation C. Decarboxylation D. Hydroxylation E. Methylation
The correct answer is E. Folic acid deficiency results in the development of macrocytic anemia that
yields macro-ovalocytes and hypersegmented neutrophils on the peripheral blood smear. Folic acid is
a pteridine vitamin that 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 and amino acid synthesis. By far the most common cause of folate deficiency is
inadequate dietary intake. Alcoholics and those with poor diets are at the highest risk for developing
this type of anemia.
Pantothenic acid is a key vitamin in acyl transfer reactions (choice A). It forms part of coenzyme A,
which transfers acyl groups in thiol esters as acetyl CoA, succinyl CoA, and other acyl CoA forms.
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Important vitamins in carboxylation reactions (choice B) include biotin and vitamin K. Biotin carries
the carboxyl group in the pyruvate carboxylase and acetyl CoA carboxylase reactions, and vitamin K
is utilized in post-translational carboxylation of amino acid residues in blood clotting factors.
Oxidative decarboxylation reactions (choice C) require thiamine (vitamin B1). Examples include the
pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes.
Ascorbic acid (vitamin C) is a coenzyme in the hydroxylation (choice D) of lysyl and prolyl residues of
collagen.
31. Which of the following inhibits the activity of acetyl-CoA carboxylase? A. Citrate B. Glucagon C. High-carbohydrate, low-fat diet D. Insulin
The correct answer is choice B. The key thing to remember here is that acetyl-CoA carboxylase
catalyzes the first 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 of fatty 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 fatty acid synthesis by a cAMP-dependent
phosphorylation of acetyl-CoA carboxylase. Conversely, glucagon stimulates fatty acid oxidation.
Clinical correlate: Glycogen metabolism is profoundly affected by specific hormones. Insulin, a
polypeptide hormone, increases the capacity of the liver to synthesize glycogen. When insulin levels
are high, the production of glycogen is high. The action of insulin is opposed by both glucagon and
epinephrine which will increase blood glucose levels.
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) would stimulate, 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-CoA carboxylase. It does so by dephosphorylating the enzyme.
- From which intermediate in the glycolytic pathway does the pentose phosphate pathway
(also known as the hexose monophosphate, or pentose, shunt) “shunt”?
A. Fructose-1,6-bisphosphate
B. Fructose-6-phosphate
C. Glucose-6-phosphate
D. Phosphoenolpyruvate
E. Pyruvate
The correct answer is C. The hexose monophosphate shunt is an alternative route for the oxidation
of glucose; it supplies the cell with NADPH and pentose sugars. The NADPH is used in many
biosynthetic processes (e.g., fatty acid and cholesterol synthesis), whereas the pentoses are involved
in the synthesis of nucleotides and some coenzymes. The pathway “shunts” from glucose-6-
phosphate, which is oxidized in a series of NADPH-generating reactions, to ribulose-5-phosphate.
The nonoxidative phase, which involves the transfer of C2 and C3 units from one sugar to another,
follows. One resulting intermediate is fructose-6-phosphate (choice B), which can serve as a re-entry
point to glycolysis, thereby closing the”shunt” loop.
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Although all the other choices are glycolytic intermediates, they are not involved in the hexose
monophosphate shunt.
- Loss of which of the following classes of molecules on the surface of a tumor cell target
would result in loss of susceptibility to killing by host immune cells?
A. CD3
B. CD4
C. CD8
D. MHC class I
E. MHC class II
The correct answer is D.Major histocompatibility complex (MHC) class I proteins are found in the
membranes of all nucleotide cells. If the cell is healthy and the peptides are normal, T cells will ignore
them. If the cytoplasm contains abnormal peptides, they will appear in the cell membrane and the T
cells will be activated which will lead to the destruction of the cell. After the MHC class I molecule has
moved to the surface of the tumor cell, peptide fragments from the tumor are presented in a groove of
the class I molecule. The peptide fragments are presented to cytotoxic CD8 T cells, which recognize
the MHC class I molecules on the cell surface and kill the tumor cell. Loss of this molecule would
therefore prevent the tumor cell from being killed.
The CD3 molecule (choice A) is a marker on all T cells. It is involved in signal transduction, but not
antigen recognition. This molecule would not be on the surface of tumor cells.
The CD4 molecule (choice B) is not on the surface of a tumor cell, but it is on the surface of a CD4+
T helper lymphocyte.
The CD8 molecule (choice C) is not on the surface of a tumor cell, but it is on the surface of a CD8+
cytotoxic T lymphocyte.
MHC class II antigens (choice E) are not involved in killing of tumor cell targets. They present peptide
fragments (derived from intracellular killing of extracellular organisms by macrophages) to CD4 T
lymphocytes.
34. Which of the following citric acid cycle intermediates is required for heme synthesis? A. a±-Ketoglutarate B. Fumarate C. Isocitrate D. Oxaloacetate E. Succinyl-CoA
The correct answer is E. The porphyrin ring of heme is derived from the citric acid cycle intermediate
succinyl-CoA and the amino acid glycine. The initial synthetic step, which is rate-limiting, is catalyzed
by aminolevulinic acid synthase (ALA synthase).
35. Which of the following metabolic processes occurs exclusively in the mitochondria? A. Cholesterol synthesis B. Fatty acid synthesis C. Gluconeogenesis D. Ketone body synthesis E. Urea cycle
The correct answer is D. Of the processes listed, only ketone body synthesis occurs exclusively in
the mitochondria. Other mitochondrial processes include the production of acetyl-CoA, the TCA cycle,
the electron transport chain, and fatty acid oxidation. The most common cause of ketone body
formation is ketoacidosis secondary to diabetes. The essential diagnostic characteristics include:
hyperglycemia, acidosis (with blood pH < 7.3), serum bicarbonate < 15 and serum positive for
ketones.
Processes that occur exclusively in the cytoplasm include cholesterol synthesis (choice A; in cytosol
or in ER) and fatty acid synthesis (choice B).
Note that gluconeogenesis (choice C) and the urea cycle (choice E) occur in both the mitochondria
and the cytoplasm.
- An infant diagnosed with phenylketonuria would be expected to be deficient in which of the
following nonessential amino acids, assuming that it is not obtained from dietary sources?
A. Asparagine
B. Cysteine
C. Glutamine
D. Proline
E. Tyrosine
The correct answer is E. The human body is able to synthesize roughly half the amino acids
necessary to build protein. These amino acids, termed nonessential, include alanine, arginine,
asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, and tyrosine. The
amino acids that must be supplied in the diet are termed essential; these include histidine, isoleucine,
leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Phenylalanine
undergoes hydroxylation to tyrosine, catalyzed by the enzyme phenylalanine hydroxylase. It is
noteworthy that tyrosine becomes an essential amino acid in individuals lacking this enzyme. The
hyperphenylalaninemias, which include phenylketonuria, result from impaired conversion of
phenylalanine to tyrosine, and are also asociated with mental retardation. This condition is associated
with increased phenylalanine in blood and increased phenylalanine and its by-products (e.g.,
phenylpyruvate, phenylacetate, and phenyllactate) in urine.
Asparagine (choice A) is a member of the “oxaloacetate family”; its immediate precursor is aspartate.
The immediate precursor of cysteine (choice B) is serine. Serine is also the precursor of the
nonessential amino acid glycine.
Glutamine (choice C), proline (choice D), and arginine are produced from glutamate. The synthesis
of glutamate occurs by the reductive amination of alpha-ketoglutarate.
