Biochemistry Qs

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BioChemistry Qs

A chronic alcoholic develops severe memory loss with marked confabulation. Deficiency of

which of the followingvitamins 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

Explanation:

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 patientmay 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 the U.S., severe

thiamine deficiency is seenmost 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.

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 with radiationto the right shoulder, especially after large or fatty meals. Her physician diagnoses

gallstones. Of which of the

Page 1 of 48BioChemistry Qs - Doctor .VG Forum



following compounds are these stones most likely composed?

A. Calcium bilirubinate

B. Calcium oxalate

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 hemolytic anemias, includingsickle cell anemia.

Bilirubin stones can also be seen in hepatic cirrhosis and liver fluke infestation.

Calcium oxalate stones (choice B) and cystine stones (choice E) are found in the kidney,

rather than thegallbladder.

Pure cholesterol stones (choice C) are less common than mixed gallstones, but have thesame risk factors,

including obesity and multiple pregnancies.

Mixed stones (choice D) are the common "garden variety" gallstones, found especially in

obese, middle agedpatients, with a female predominance.

Two sisters are diagnosed with hemolytic anemia. Their older brother was previously

diagnosed with the same

disorder. Two other brothers are asymptomatic. The mother and father are second cousins.

Deficiency of which of

the following enzymes would be most 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 in

glycolysis or thehexose monophosphate shunt (pentose phosphate pathway). Only two enzymes of those

listed in the answer

choices specifically involve these pathways and cause hemolytic anemia: pyruvate kinaseand

glucose-6-phosphate dehydrogenase. Glucose-6-phosphate dehydrogenase (G6PD)

deficiency is inherited as

an X-linked recessive trait, so females would not be affected. Pyruvate kinase is a glycolytic

enzyme; pyruvatekinase 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 storagediseases.

Glucose-6-phosphatase dehydrogenase (choice C) deficiency produces an X-linked hemolyticanemia.

Defects in muscle phosphorylase (choice D) produce McArdle's disease, one of the glycogen

storage diseases.

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

F. Tryptophan

Explanation:

The correct answer is B. This question requires two logical 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 ishydrophilic. 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 of 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 (choice F)

have aromatic

side chains.

A Southeast Asian immigrant 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

Explanation:

The correct answer is B. The disease is cretinism, characterized by a profound lack of thyroid

hormone in adeveloping 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.

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.

To which of the following diseases is pyruvate kinase deficiency most similar clinically?

A. α-thalassemia

B. β-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 characterized clinically by long "normal" periodsinterspersed 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 α(choice A) and β(choice B) thalassemias, in their major forms, arecharacterized 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-phosphate dehydrogenase deficiency, oxidant drugs are not aspecific 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 to show a delay in motor development by

3 months of age. Atone year of age, the child begins to develop spasticity and writhing movements. At age

three, compulsive biting of




fingers and lips and head-banging appear. At puberty, the child develops arthritis, and death

from renal failure

occurs at age 25. This patient's condition is due to an enzyme deficiency in which of the

following biochemical

pathways?

A. Ganglioside metabolism

B. Monosaccharide metabolism

C. Purine metabolism

D. Pyrimidine metabolism

E. Tyrosine metabolism

Explanation:

The correct answer is C. The patient has a classical case of Lesch-Nyhan syndrome, an X-

linked disorder due

to severe deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyl

transferase (HPRT).This defect is associated with excessive de novo purine synthesis, hyperuricemia, and the

clinical signs and

symptoms described in the question stem. The biochemical basis 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 and reduces 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 a

self-imposed "starvation diet" for four months, and has lost 60 pounds while consuming only

water and vitamin

pills. If extensive blood studies were performed, which of the following would be expected tobe elevated?

A. Acetoacetic acid

B. Alanine

C. Bicarbonate

D. Chylomicrons

E. Glucose




Explanation:

The correct answer is A. Long-term starvation induces many biochemical changes. Much of the body's energy

requirements are normally supplied by serum glucose, but in starvation are supplied by both

glucose andlipid-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 in the 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

the ketone

bodies.

Chylomicrons (choice D) are the lipid form seen after absorption 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 skin. The

patient has nearly white hair, pink irises, very pale skin, and a history of burning easily whenexposed to the sun.

This patient's condition is caused 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 deficiencyof copper-dependent tyrosinase (tyrosine hydroxylase), blocking the production of melanin

from the aromatic




amino acid tyrosine. Affected individuals lack melanin pigment in skin, hair, and eyes, 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 (choiceB) causing motor

abnormalities and seizures.

Tay-Sachs disease is an example of a disorder of glycolipids (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). Thismucopolysaccharidosis is

inherited as an autosomal recessive trait.

Homocystinuria disease is an example of a disorder of sulfur-containing amino acids (choice

E).

A 7-year-old boy is referred to a specialty clinic because of digestive problems. He often

experiences severe

abdominal cramps after eating a high fat meal. He is worked up and diagnosed with a

genetic defect resulting in adeficiency 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 theintestinal mucosal cells.

They are assembled in chylomicrons and eventually sent into the circulation for delivery to

adipocytes andother cells. Chylomicrons are too large to enter cells, but are degraded 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 patient after a high fat meal. However, VLDLwould be elevated

if the patient ate a high carbohydrate meal. In this situation, the carbohydrate would be

converted into fat in theliver and sent out into circulation as VLDL. VLDL would be unable to be degraded to LDL and,

therefore, would

accumulate.

A defect in lipoprotein lipase would cause a decrease, not an elevation of unesterified fattyacids (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 examination

reveals 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. Successful therapy should be aimed at increasing which of thefollowing 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 autosomaldominant disorder affecting about 1 in 500 persons. The xanthomas on the Achilles tendon

and the arcus

lipoides (the opaque rings in the eye) are pathognomonic. Affected individuals have veryhigh LDL cholesterol

because of deficient endocytosis 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 LDLreceptors (i.e., apo B-100 receptors) to enhance clearance of LDL particles. Dietary changes,

a resin drug,




niacin, or an HMG-CoA reductase inhibitor could be tried.

Apo B-100 (choice A) is the apoprotein of liver-produced lipoproteins 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 found in the hepatocyte membrane.

Apo E receptor (choice D) would actually be increased by the treatment withhypocholesterolemic 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 HDL cholesterol and apo AI are inversely related to the risk of coronary heart disease.

Which of the following structures is common to all sphingolipids?

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 of

membranes.

Ceramide is a component of sphingolipids. Ceramide is composed of sphingosine, a long-chain amino alcohol

with a saturated fatty acid linked to the amino group. Sphingolipids can be differentiated onthe basis of the "X"

group that is esterified to the terminal hydroxyl group of ceramide.

Carnitine (choice A) is involved in the oxidation of fatty acids. 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 polar head that distinguishes 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 myelinsheath.

Squalene (choice E) is a 30-carbon intermediate in the synthesis of cholesterol.

A 47-year-old male patient presents with painful arthritis in the right big toe and uric acidrenal 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

E. Increased levels of leukotrienes

Explanation:

The correct answer is B. This patient has gout, characterized by painful joints due to theprecipitation of uric

acid crystals caused by excessive production of uric acid (a minority of cases are associated

withunderexcretion of uric acid). Kidney disease is also seen due to accumulation of uric acid in

the tubules. The

disease mostly affects males, and is frequently treated with allopurinol, an inhibitor of

xanthine oxidase.

Xanthine oxidase catalyzes the sequential oxidation of hypoxanthine to xanthine to uric acid.

A defect in urea synthesis (choice A) would result in the accumulation of ammonia.

Phenylketonuria is a disease in which tyrosine cannot be produced from phenylalanine

(choice C). It is

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

tobronchoconstriction.




A newborn vomits after each feeding of milk-based formula, and does not gain weight.

Biochemical testing reveals

a severe deficiency of galactose-1-phosphate uridyltransferase, consistent withhomozygosity. If this condition

goes untreated, what is the likely outcome 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 galactokinaseproduces very mild disease with the only significant complication being cataract formation.

In contrast,

homozygous deficiency of galactose-1-phosphate uridyltransferase produces severe diseaseculminating in

death in infancy. In addition to galactosemia and galactosuria, these patients have impaired

renal tubular

resorption leading to aminoaciduria, gastrointestinal symptoms, hepatosplenomegaly,

cataracts, bleedingdiathesis, hypoglycemia, and mental retardation. Pathologically, the CNS shows neuronal

loss and gliosis and

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

uridyltransferasedeficiency, 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 in homozygous galactose-1-phosphate

uridyltransferase

deficiency, but they would not be expected to remit with puberty. Instead, most untreatedinfants with this

disorder show failure to thrive 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 andrequired a special diet. Tests confirm markedly elevated maternal serum levels of

phenylalanine and phenylacetic

acid. Genetic studies have not been performed on the father. What should the physician tellthe 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

are elevated, acts asa teratogen to the developing fetus. This condition is known as maternal PKU. Although the

mother can fare well

with substantial elevations in serum phenylalanine concentration, the children born to such

women are usually

profoundly retarded and may have multiple birth defects.

Although dietary modifications (choice A) can prevent the neurological and dermatologic

manifestations of PKUin a child, the fetus is still at risk from maternal PKU.

Further information regarding the cause of this woman's hyperphenylalaninemia (choice B) is

not needed, 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 PKUgene (choice C). Fetal phenylalanine hydroxylase cannot compensate for the high maternal

levels of

phenylalanine.

The critical period in development during which teratogenic materials affect the growing

organs is between the

3rd and 8th weeks of gestation. By the end of the 2nd month (compare with choice D), the

damage caused bythe maternal PKU has already occurred.




A 24-year-old graduate student presents to a physician with complaints of severe muscle

cramps and weakness

with even mild exercise. Muscle biopsy demonstrates glycogen accumulation, but hepatic

biopsy is unremarkable.Which of the following is the most 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 of these involve the liver. McArdle's disease (Type Vglycogen storage

disease), due to a defect in muscle phosphorylase, is restricted to skeletal muscle. The

presentation describedin the question stem is typical. Many affected individuals also experience myoglobinuria.

Definitive diagnosis is

based on 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 storage disease 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, only ketone body synthesis occurs

exclusively in themitochondria. Other mitochondrial processes include 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 hexose monophosphate shunt

(choice E).

Note that gluconeogenesis (choice C) and the urea cycle (choice G) occur in both the

mitochondria and thecytoplasm.

A physician from the United States decides to take a sabbatical 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 is told that

he will be seeing apatient with glucose-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 classic presentation of glucose-6-phosphatedehydrogenase deficiency is

a child who eats a meal of beans (Vicia fava) and several hours later develops




hemoglobinuria 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 in total hemoglobin and a rise in free

plasma hemoglobin,accompanied by a rise in unconjugated bilirubin and a fall in haptoglobin. The episode

usually resolves

spontaneously several days later. Today, the classic presentation is less common indeveloped countries than

is a slower onset syndrome beginning 1-3 days after starting an antimalarial drug,

sulfonamide, or other

antioxidant drug. Rarely, glucose-6-phosphate dehydrogenase deficiency presents as

neonatal jaundice or withchronic hemolysis.

A patient with familial hypercholesterolemia undergoes a detailed serum lipid and lipoprotein

analysis. Studiesdemonstrate elevated cholesterol in the form of increased LDL without elevation of other

lipids. This patient's

hyperlipidemia is best classified as which of the following types?

A. Type 1

B. Type 2a

C. Type 2b

D. Type 3

E. Type 5

Explanation:

The correct answer is B. Hyperlipidemia has been subclassified based on the lipid and

lipoprotein profiles. Type

2a, which this patient has, can be seen in a hereditary form, known as familial

hypercholesterolemia, and also insecondary, acquired forms related to nephritic syndrome and hyperthyroidism. The root

problem appears to bea deficiency of LDL receptors, which leads to a specific 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 elevation of chylomicrons.

Type 2b (choice C) is characterized by elevations of both cholesterol 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

of VLDL andchylomicrons.

During the isolation of Met-enkephalin (Tyr-Gly-Gly-Phe-Met) from post-mortem humanbrain tissue, researchers find

that the peptide is rapidly degraded by peptidases in 1 minute at 37 C. Detailed analysis of

the peptide cleavagepattern of Met-enkephalin is investigated with two candidate enzymes. Using the drug

bestatin, the investigators

found 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 degradative pathway

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 humanbrain, undergoes two

routes of metabolism. One route releases a tripeptide and therefore is the result of apeptidase that cuts an amino

acid bond within the molecule: an endopeptidase. The other route releases free tyrosine and

therefore is anexopeptidase. Exopeptidases can remove amino acid residues from the amino- or carboxyl-

terminus of the protein.

By convention, all peptide 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 digestionby an aminopeptidase.




The scientists have used two drugs to highlight the two enzymatic pathways. With bestatin,

Met-enkephalin is

metabolized only to the tripeptide; therefore bestatin inhibits the aminopeptidase enzyme,

preventing release of free

tyrosine residues. With thiorphan, Met-enkephalin is metabolized to free tyrosine; thetripeptide is no longer formed.

Thiorphan is an inhibitor of the endopeptidase. The lack of persistence of Met-enkephalin in

the presence of anenzyme inhibitor is evidence that the peptide's metabolism is shifted in the direction of the

noninhibited enzyme. A

schematic of the metabolism would be:

Tyrosine cannot be the result of carboxypeptidase activity (choice B), since the carboxyl-

terminus of Met-enkephalinis a methionine.

Bestatin inhibits an aminopeptidase, not an endopeptidase (choice C). An endopeptidasewould not release a free

amino acid residue.

Met-enkephalin is indeed metabolized by an aminopeptidase and an endopeptidase, but

bestatin inhibits theaminopeptidase and thiorphan inhibits the endopeptidase (compare with choice D).

Thiorphan does not inhibit an aminopeptidase (choice E); furthermore, such an enzymewould release a free Tyr

and a tetrapeptide.

The parents of a 6-month-old child who was normal at birth bring her into the clinic. Sincetheir emigration to the

U.S. from Eastern Europe soon after her birth, the child has developed diminished

responsiveness, progressiveblindness 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 sufferfrom diminished

responsiveness, deafness, blindness, loss of neurologic function, and seizures. A cherry-red

spot on the maculamay 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 theenzyme.

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 andurine. Clinically,

there is a musty body odor and mental retardation.

Hypophosphatemic rickets is an X-linked dominant condition causing abnormal regulation of

vitamin D3 (choiceE) 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 productionis 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 inmaintaining the Na+/

K+ exchange across the plasmalemma is actually the most immediately important function

for most cells. Thedirect 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 concentrationgradient. 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 significanthypoxia 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 asfructosuria.

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 toevolution 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 phosphatecondenses with aspartate

to form carbamoyl aspartate, in a reaction catalyzed by aspartate transcarbamoylase. In

subsequent steps, ringclosure 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 purinesynthesis. 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 andmetabolites. Activity of

which of the following enzymes was most likely increased in the patient's myocardial cells

shortly prior to hisdeath?

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 infarctionof 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 itsactivity would therefore

be increased.

Phosphoenolpyruvate carboxykinase (choice A) is a regulatory enzyme in gluconeogenesis,

which is induced bycortisol, 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 isonly 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 indisorders 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 noticedyellow-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 bymental 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 retardedgrowth 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 competitiveinhibitor?

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) areboth 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 alcoholdehydrogenase, 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 (choiceA); inhibiting gluconeogenesis rather than stimulating it (choice B); inhibiting, rather than

stimulating (choice C)

glycerophosphate dehydrogenase; and favoring the formation of lactate rather thanpyruvate 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 withoutsupport. The physician interviews the parents and ascertains that they are both Ashkenazic

Jews. The doctorshould 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'sdisease 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 seenwith 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 issignificant 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 symptomsare 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 storagedisease 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-Pickdisease rather than Tay-Sachs.

Hunter syndrome (choice A) is a mucopolysaccharidosis, inherited in an X-linked recessivefashion.

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.

26 [IMG]file:///C:/DOCUME%7E1/Owner/LOCALS%7E1/Temp/msohtml1/01/clip_image002.jpg

[/IMG]

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 mitochondrial membrane. It reforms fatty acyl CoA inthe mitochondrial matrix

(arrow 5) from acyl carnitine, thus preparing it for mitochondrial oxidation. The acyl groups

on carnitine are derived

from acyl CoA esters synthesized in the outer mitochondrial membrane, which are made

from free fatty acidscirculating in the blood.




Fatty acyl CoA synthetases (choice B) are located in the outer mitochondrial

membrane, indicated by arrow 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 byarrow 3.

Arrow 4 indicates smooth endoplasmic reticulum.

A 72-year-old woman, in otherwise good health, presents with megaloblastic anemia.

Careful evaluation revealsa folate deficiency as the cause of the anemia. Assuming the folate deficiency is due to

dietary causes, which of

the following is the most likely problem?

A. Lack of leafy green vegetables

B. Lack of milk products

C. Lack of red meat

D. Lack of yellow vegetables

E. Overcooked food

Explanation:

The correct answer is E. Folates (pteroylglutamic acid and related compounds) are widelydistributed in

foodstuffs. Dietary deficiency is usually due to overcooked (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, she witnesses a

seizure. Physical examination is remarkable for hepatomegaly, a finding later confirmed byCT 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 adeficiency of

glucose-6-phosphatase. It typically presents with neonatal hypoglycemia, hyperlipidemia,

lactic acidosis, andketosis. Failure to thrive is common in early 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 of these 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, but McArdle's (choice B) and Pompe's(choice D) disease

affect muscle rather than liver and would not be expected to produce profound

hypoglycemia, since the liver isthe major source for blood glucose.

A newborn appears normal at birth, but develops vomiting and diarrhea accompanied by

jaundice andhepatomegaly within the first few weeks of life. Within months, the baby has obvious

cataracts and ascites. Theinfant is switched to a milk-free diet, which stabilizes but does not completely reverse his

condition. By one year of

age, he has developed mental retardation. Which of the following is the most likelydiagnosis?

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 is necessary for the metabolism of the

galactose derived frommilk lactose. The condition should be suspected in infants with growth failure, cataracts, liver

disease,

aminoaciduria, and mental retardation. A reducing sugar (galactose) is usually present in theurine. Most of the

pathology is related to the toxic effects of galactose-1-phosphate. Treatment involves strict

dietary lactoserestriction, which consists of more than simply withdrawal of milk products, because lactose

is also present 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 pulmonary

disease.

McArdle's disease (choice C) is a glycogen storage disease that selectively affects muscle.

Von Gierke's disease (choice D) is a glycogen storage disease affecting the liver and kidneys.

Wilson's disease (choice E) is a caused by a metabolic abnormality in the handling of copperthat 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 of glycolysis are catalyzed by

hexokinase,

phosphofructokinase-1 (choice B), and pyruvate kinase. In gluconeogenesis, other enzymes

are needed tobypass these key steps. Pyruvate cannot be directly converted to phosphoenolpyruvate in

gluconeogenesis.

Therefore, pyruvate carboxylase (a mitochondrial enzyme; choice A) converts pyruvate tooxaloacetate, which

can be converted to phosphoenolpyruvate by phosphoenolpyruvate carboxykinase (choice

D), using two ATP

equivalents per molecule of phosphoenolpyruvate. Fructose-1,6-bisphosphatase (choice A) is

the enzyme thatsplits fructose-1,6-bisphosphate into fructose-6-phosphate and inorganic phosphate. It is

also required for

gluconeogenesis.

Glucose-6-phosphatase (choices B and C) is a liver enzyme that hydrolyzes glucose-6-

phosphate to glucose. Adeficiency of this enzyme leads to von Gierke disease, also known as glycogen storage

disease type I.

Pyruvate dehydrogenase (choice C) is a mitochondrial enzyme that converts pyruvate to

acetyl CoA. Thisenzyme requires thiamine pyrophosphate, lipoamide, and FAD as cofactors.

Glucokinase (choice D) is a liver enzyme that converts glucose to glucose-6-phosphate.Unlike hexokinase, it is

specific for glucose and is unresponsive to the level of glucose-6-phosphate. Its function 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 glucose is very high.

Pyruvate kinase (choice E) catalyzes the conversion of phosphoenolpyruvate to pyruvate inthe glycolytic

pathway. It is activated by fructose-1,6-bisphosphate, the product of the committed step of

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 astrict fat-free diet. Her alopecia is probably related to a deficiency of which 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 cancause 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.

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 cell

membranes.

Vitamin K (choice E) is necessary for normal blood coagulation.

5 mL of synovial fluid is aspirated from an inflamed knee joint. The fluid is yellow-white and

cloudy and contains

200,000 WBC/mm3 (85% neutrophils). Needle-shaped, strongly negatively birefringentcrystals are seen both

within and outside neutrophils. These crystals most likely have which of the following

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 only

monosodium urate

(associated with gout) and calcium pyrophosphate dihydrate (associated with CPPD crystal

deposition disease,

also called pseudogout), and to lesser degree basic calcium phosphate (apatite-associatedarthropathy), have

a high likelihood of being encountered on a step 1 USMLE exam. 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,

since the sodium salt is the predominant species in vivo.

Basic calcium phosphate (choice A) is seen in apatite-associated arthropathy and producesspherical 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

D. Vitamin B5

E. Vitamin B6

Explanation:

The correct answer is A. Vitamin B1, or thiamine, is the coenzyme required (as thepyrophosphate) 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 thiaminepyrophosphate 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.

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.

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.

Vitamin B5(choice D), or pantothenic acid, is conjugated with coenzyme A to act as acarboxylic 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 analysis revealselevated 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 conversionof pyruvate to

acetyl-CoA. If PDH is absent, pyruvate will be used in other pathways instead. Pyruvate will

be converted toalanine 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 ureasynthesis. Deficiency of this enzyme would not cause the symptoms described.




Pyruvate carboxylase (choice D) is a gluconeogenic enzyme that catalyzes the conversion of

pyruvate to

oxaloacetate. Deficiency of this enzyme would not cause 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 citrate synthase from acetyl CoA and

oxaloacetate. This reactiontakes place in the mitochondria, but citrate can move freely from the mitochondria into the

cytosol. When the

citric acid cycle slows down, citrate accumulates. In the cytosol, it acts as a negativeallosteric 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

acid cycle. 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 tooxaloacetate. It is important

in gluconeogenesis and replenishes the oxaloacetate in the citric acid cycle.

6-phosphogluconate dehydrogenase (choice E) converts 6-phosphogluconate to ribulose 5-

phosphate in thepentose phosphate shunt pathway.

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

Explanation:

The correct answer is 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 mightbe involved in

either the breakdown of glycogen to glucose (glycogenolysis) or in the creation of glucose

fromnoncarbohydrate 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) is involved 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 inhibitedby 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.

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 the first andrate-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,

glucagonstimulates fatty acid oxidation.

Citrate (choice A) is a key player in fatty acid synthesis (citrate shuttle). Therefore, thepresence 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 andtherefore would stimulate acetyl-CoA carboxylase. It does so by dephosphorylating the

enzyme.

An individual lacking the enzyme tyrosinase would be particularly predisposed to develop

which of the following?

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 biosyntheticpathway for melanin formation from tyrosine. A lack of tyrosinase causes one form of

albinism; 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 patientscannot form melanin.

A newborn baby has multiple hemorrhages. Clotting studies demonstrate an elevated

prothrombin time. An

abnormality of which of the following biochemical processes 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 an elevated

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 Factors II(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 (choice A) 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 easybruising, but will not

prolong the prothrombin time.

A very ill infant is admitted to the hospital. Laboratory examination reveals a very high

serum concentration of

lactic acid. In addition to taking steps to correct the acidosis, the attending physicianprescribes 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-soluble vitamin that is converted to the

coenzyme thiaminepyrophosphate. This coenzyme is used by pyruvate dehydrogenase to convert pyruvate to

acetyl coenzyme A.

In the absence of thiamine, pyruvate accumulates and can be converted by lactate

dehydrogenase to lactate,

which is spilled in the blood causing lactic acidosis.

Lactate dehydrogenase (choice A) produces lactate from pyruvate 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 thiamine pyrophosphate.

Pyruvate kinase (choice D) makes pyruvate from phosphoenolpyruvate, but does not use

thiamine

pyrophosphate.

Transketolase (choice E) requires thiamine pyrophosphate, but operates in another pathway

(pentose

phosphate pathway). Decreased transketolase activity is not associated with the

development of lactic acidosis.

A 69-year-old edentulous alcoholic male who lives alone is admitted to the hospital forevaluation of a shoulder

wound that is not healing well. On physical examination, numerous ecchymoses are noted

on the posterioraspect 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 14-18 g/dL); no other hematologic abnormalities are noted. Therapy should consistof




A. administration of factor VIII

B. administration of iron

C. administration of vitamin B12

D. administration of vitamin C

E. administration of vitamin K

Explanation:

The correct answer is D. The patient described suffers from 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 vessel walls. Clinically, the deficiency syndrome ischaracterized 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 be indicated for factor VIII deficiency, whichwould 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 ahypochromic, microcytic anemia in this patient. 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 to concomitant 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 Kdeficiency, which would

produce prolongations of the prothrombin time (PT), followed eventually by prolongation of

the PTT as thevitamin 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 often severely impaired, with consequent steatorrhea and deficiency of

fat-solublevitamins, including vitamin A.

Cystinuria (choice A) is a relatively common disorder in which a defective transporter fordibasic amino acids

(cystine, ornithine, lysine, arginine; COLA) leads to saturation of the urine with cystine,

which is not very soluble

in urine, and precipitates out to form stones.

Hypoglycemia (choice B) is not a prominent feature of children 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 any regularity in children with cystic

fibrosis.

Sphingomyelin accumulation (choice D) is generally associated with deficiency of

sphingomyelinase, as seen inNiemann-Pick disease.

In which of the following laboratory tests would you expect to find the greatest disparity inreference 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 and

hemoglobin (Hb) concentration in blood. The normal reference interval for Hb concentrationin 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 ishigher 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 averageof 1000 mg of iron

for men. In the absence of inflammation, the small circulating fraction of ferritin (choice C)

correlates well with

ferritin stores in the bone marrow. Hence, men have different reference intervals for serum

ferritin than dowomen (15-200 ng/mL in men versus 12-150 ng/mL in women).

The mean corpuscular volume (choice A), serum alkaline phosphatase (choice B), serumglucose (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:

The correct answer is B. Substances that reduce the activity of an enzyme are called

inhibitors. Reversible

inhibitors bind to an enzyme but rapidly dissociate from it [in contrast to irreversibleinhibitors (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

active site (choice

B). Thus, increasing the concentration of substrate will decrease the percent inhibition of theenzyme. 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 notaltered. 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 free enzyme, but binds to the enzyme-substratecomplex at a site

other than the catalytic site. Once bound by the inhibitor, the enzyme is trapped in the

enzyme-substrate

complex state until the inhibitor dissociates. In this kind of inhibition, the slope of the

reaction (which is the ratioKm/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-rayshows biventricular dilation of the heart. Deficiency of which of the following vitamins 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 most frequently encountered in alcoholicsand in developing

countries. Deficiency of this vitamin can take several forms: dilated cardiomyopathy




(“wet beriberi

&rdquo , polyneuropathy (“dry beriberi&rdquo , and mamillary body degeneration

(Wernicke-Korsakoff

syndrome).

Ascorbic acid (choice A, Vitamin C) deficiency causes scurvy, associated with capillary

fragility, bony

abnormalities, and poor wound healing.

Retinol (choice B, Vitamin A) deficiency causes blindness and impaired immune responses.

Riboflavin ( choice C) deficiency causes cheilosis, glossitis, and dermatitis.

Vitamin K (choice E) deficiency causes impaired blood clotting because of decreased

production of factors II,

VII, IX, and X.

A 2-month-old child is evaluated for failure to thrive. As the pediatrician is examining the

child, a convulsion

occurs. Stat serum chemistries demonstrate severe hypoglycemia, hyperlipidemia, lactic

acidosis, and ketosis.

Physical examination is remarkable for hepatomegaly, a finding confirmed by CT scan, whichalso 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 with neonatal hypoglycemia, hyperlipidemia,

lactic acidosis, and

ketosis. Failure to thrive is common in early life; convulsions may occur due to profoundhypoglycemia. The

glycogen accumulation in von Gierke's disease occurs primarily in the liver and kidneys,

accounting for the

enlargement of these 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 notbe 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 be expected 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.Erythropoiesis is

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

Explanation:

The correct answer is E. Folic acid is a pteridine vitamin that exists as tetrahydrofolate (TH4)

in its mostreduced 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, whichtransfers 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, and vitamin K isutilized in

post-translational carboxylation of amino acid residues in blood clotting factors.

Oxidative decarboxylation reactions (choice C) require thiamine (vitamin B1). Examples

include the pyruvatedehydrogenase and alpha-ketoglutarate dehydrogenase complexes.




Ascorbic acid (vitamin C) is a coenzyme in the hydroxylation (choice D) of lysyl and prolyl

residues of collagen.

A 10-year-old child is suspected of having pellagra because of chronic symptoms including

diarrhea, a red scalyrash, and mild cerebellar ataxia. However, his diet is not deficient in protein and he appears

to be ingesting

adequate amounts of niacin. A sister has a similar problem. Chemical analysis of his urinedemonstrates large

amounts of free amino acids. Which of the following is the most likely diagnosis?

A. Alkaptonuria

B. Carcinoid syndrome

C. Ehlers-Danlos syndrome

D. Hartnup's disease

E. Scurvy

Explanation:

The correct answer is D. The child has Hartnup's disease. This condition clinically resembles

pellagra("diarrhea, dementia, and dermatitis"), and may be misdiagnosed as this nutritional (niacin)

deficiency. In fact,

niacin therapy may actually be helpful in controlling the symptoms. The underlying problem

is a defect in the

epithelial transport of neutral amino acids, including tryptophan, which can act as aprecursor of niacin. The

defective amino acid transport leads to poor absorption of dietary amino acids as well as

excess amino acidsecretion in the urine.

Alkaptonuria (choice A) is characterized by urine that turns black upon standing and a

debilitating arthritis.

Carcinoid syndrome (choice B) is seen in patients with carcinoid tumor. It is characterized byepisodes of

flushing, diarrhea, hypertension, and bronchoconstriction.

Ehlers-Danlos syndrome (choice C) is a disease characterized by abnormal collagen

formation leading to veryelastic skin, joint problems, and fragility of some blood vessels and the intestines.

Scurvy (choice E) is due to vitamin C deficiency. It is characterized by easy bruising and

gum problems.




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

Explanation:

The correct answer is D. Remember that a buffer is most effective when its pKa is within the

pH range of the

surrounding medium. Histidine is the only amino acid with good buffering capacity at

physiologic pH. The

imidazole side chain of histidine has a pKa around 6.0 and can reversibly donate and acceptprotons 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.

An 8-month-old female child is brought to medical attention because her first four teeth

show several discrete,

discolored, circumferential bands that show very little enamel. Excessive levels of which of

the following may haveproduced this defect?

A. Bilirubin

B. Fluoride

C. Parathormone

D. Thyroid hormone

E. Vitamin C




Explanation:

The correct answer is B. Fluoride excess causes direct injury to ameloblasts, leading toinadequate production

of tooth enamel. The resultant defect in enamel production causes recessed and discolored

rings on theemerging teeth. Other conditions that cause enamel hypoplasia include inadequate levels of

calcium,

phosphorus, and vitamins A, C, or D, hypothyroidism, and hypoparathyroidism.

Jaundice in the newborn period may cause bilirubin (choice A) deposition in the developingteeth, resulting in

pigmented, but otherwise normal teeth.

Hyperparathyroidism (choice C), with resultant hypercalcemia, will result in osteoporosis,

renal stones, and

neuromuscular weakness, but no obvious dental changes. Enamel hypoplasia is associatedwith

hypoparathyroidism.

Hyperthyroidism (choice D) characteristically produces cardiac and nervous disturbances,

weight loss,hypermetabolism, and proptosis, but does not cause enamel hypoplasia. Hypothyroidism,

not hyperthyroidism,

produces enamel hypoplasia.

Excess dietary vitamin C (choice E) is generally excreted in the urine and produces no

systemic pathology.

Scurvy, due to inadequate vitamin C, may produce enamel hypoplasia.


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