nishi's qb - biochemistry

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* biochem

#128673nishi - 10/15/06 19:39

A chronic alcoholic develops severe memory loss with

marked confabulation. Deficiency of which of the

following vitamins would be most likely to contribute tothe neurologic damage underlying these

symptoms?

A. Folic acid

B. Niacin

C. Riboflavin

D. Thiamine

E. Vitamin B12

Explanation:

The correct answer is D. Wernicke-Korsakoff syndrome

refers to the constellation of neurologicsymptoms caused by thiamine deficiency. Among these,

a severe memory deficit, which the patient may

attempt to cover by making up bizarre explanations(confabulation), is prominent. Anatomical damage

to the mamillary bodies and periventricular structures

has been postulated as the cause. In theU.S., severe thiamine deficiency is seen most commonly

in chronic alcoholics. Thiamine deficiency

can also damage peripheral nerves ("dry" beriberi) andthe heart ("wet" beriberi).

Folic acid deficiency (choice A) produces megaloblasticanemia without neurologic symptoms.

Niacin deficiency (choice B) produces pellagra,characterized by depigmenting dermatitis, chronic

diarrhea, and anemia.

Riboflavin deficiency (choice C) produces ariboflavinosis,characterized by glossitis, corneal

opacities, dermatitis, and erythroid hyperplasia.

Vitamin B12 deficiency (choice E) produces

megaloblastic anemia accompanied by degeneration of

theposterolateral spinal cord.

A 25-year-old woman with sickle cell anemia complains

of steady pain in her right upper quadrant withradiation to the right shoulder, especially after large or

fatty meals. Her physician diagnoses

gallstones. Of which of the following compounds are

these stones most likely composed?

A. Calcium bilirubinate

B. Calcium oxalate

em - USMLE Forum Archives http://www.usmleforum.com/archives/2006/1/12

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C. Cholesterol

D. Cholesterol and calcium bilirubinate

E. Cystine

Explanation:

The correct answer is A. Bilirubin is a degradative

product of hemoglobin metabolism. Bilirubin(pigment) stones are specifically associated with

excessive bilirubin production in hemolyticanemias, including sickle cell anemia. Bilirubin stones

can also be seen in hepatic cirrhosis andliver fluke infestation.

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

the gallbladder.

Pure cholesterol stones (choice C) are less common thanmixed gallstones, but have the same risk

factors, including obesity and multiple pregnancies.

Mixed stones (choice D) are the common "garden

variety" gallstones, found especially in obese,

middle aged patients, with a female predominance.

Two sisters are diagnosed with hemolytic anemia. Their

older brother was previously diagnosed with thesame disorder. Two other brothers are asymptomatic.

The mother and father are second cousins.

Deficiency of which of the following enzymes would bemost likely to cause this disorder?

A. Debranching enzyme

B. Glucose-6-phosphatase

C. Glucose-6-phosphate dehydrogenase

D. Muscle phosphorylase

E. Pyruvate kinase

Explanation:

The correct answer is E. In general, you should associate

hemolytic anemia with defects inglycolysis or the hexose monophosphate shunt (pentose

phosphate pathway). Only two enzymes of those

listed in the answer choices specifically involve these

pathways and cause hemolytic anemia:pyruvate kinase and glucose-6-phosphate

dehydrogenase. Glucose-6-phosphate dehydrogenase

(G6PD)

deficiency is inherited as an X-linked recessive trait, so

females would not be affected. Pyruvatekinase is a glycolytic enzyme; pyruvate kinase deficiency

is an autosomal recessive disorder,affecting males and females approximately equally. If

this enzyme is deficient, red cells have

trouble producing enough ATP to maintain the Na+/K+pump on the plasma membrane, secondarily causing

swelling and lysis.

Debranching enzyme (choice A) defects produce Cori's

disease, one of the glycogen storage diseases.

Defects in glucose-6-phosphatase (choice B) produce

Von Gierke's disease, one of the glycogen


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storage diseases.

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

Defects in muscle phosphorylase (choice D) produce

McArdle's disease, one of the glycogen storagediseases.

Which of the following amino acids would most likely befound on the surface of a protein molecule?

A. Alanine

B. Arginine

C. Isoleucine

D. Leucine

E. Phenylalanine

F. Tryptophan

Explanation:

The correct answer is B. This question requires twological steps: first, you need to appreciate

that the hydrophilic amino acids are more likely to

appear on the surface of a protein molecule,while hydrophobic amino acids are most likely be found

in its interior. Next, you need to figure out

which of the amino acids listed is hydrophilic. If yourecall that arginine is a basic amino acid

that is positively charged at physiologic pH, you should

be able to answer this question right away.

All of the other choices have neutral side chains and are

uncharged at physiologic pH. They wouldmost likely be found in the hydrophobic core of the

protein structure. Alanine (choice A),

isoleucine (choice C), and leucine (choice D) all havealiphatic side chains; phenylalanine (choice

E) and tryptophan (choice F) have aromatic side chains.

A Southeast Asian immigrant child is noted to beseverely retarded. Physical examination reveals a pot-

bellied, pale child with a puffy face. The child's tongue is

enlarged. Dietary deficiency of whichof the following substances can produce this pattern?

A. Calcium

B. Iodine

C. Iron

D. Magnesium

E. Selenium

Explanation:

The correct answer is B. The disease is cretinism,

characterized by a profound lack of thyroid

hormone in a developing child, leading to mentalretardation and the physical findings described in

the question stem. Cretinism can be due to dietary

deficiency of iodine (now rare in this countrybecause of iodized salt), to developmental failure of

thyroid formation, or to a defect in thyroxine


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synthesis.

Calcium deficiency (choice A) in children can causeosteoporosis or osteopenia.

Iron deficiency (choice C) can cause a hypochromic,

microcytic anemia.

Magnesium deficiency (choice D) is uncommon, but can

cause decreased reflexes, and blunts theparathyroid response to hypocalcemia.

Selenium deficiency (choice E) is rare, but may cause a

reversible form of cardiomyopathy.

To which of the following diseases is pyruvate kinase

deficiency most similar clinically?

A. -thalassemia

B. -thalassemia

C. Glucose-6-phosphate dehydrogenase deficiency

D. Hereditary spherocytosis

E. Iron deficiency anemia

Explanation:

The correct answer is C. Both pyruvate kinase deficiency

and glucose-6-phosphate dehydrogenase

deficiency are red cell enzyme deficiencies characterizedclinically by long "normal" periods

interspersed with episodes of hemolytic anemia

triggered by infections and oxidant drug injury(antimalarial drugs, sulfonamides, nitrofurans). In both

of these conditions, the cell morphology

between hemolytic episodes is usually normal or close tonormal.

The (choice A) and (choice B) thalassemias, in theirmajor forms, are characterized by

persistent severe anemia. In the trait forms, they are

charactertized by mild anemia.

Hereditary spherocytosis (choice D) is characterized by

intermittent hemolysis, but, unlike pyruvate

kinase deficiency and glucose-6-phosphatedehydrogenase deficiency, oxidant drugs are not a

specific

trigger for hemolysis.

Iron deficiency anemia (choice E) is characterized by

chronic anemia with hypochromic, microcytic

erythrocytes.

A baby that was apparently normal at birth begins toshow a delay in motor development by 3 months of

age. At one year of age, the child begins to developspasticity and writhing movements. At age three,

compulsive biting of fingers and lips and head-banging

appear. At puberty, the child developsarthritis, and death from renal failure occurs at age 25.

This patient's condition is due to an

enzyme deficiency in which of the following biochemicalpathways?

A. Ganglioside metabolism

B. Monosaccharide metabolism


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C. Purine metabolism

D. Pyrimidine metabolism

E. Tyrosine metabolism

Explanation:

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

disorder due to severe deficiency of the purine salvageenzyme hypoxanthine-guanine phosphoribosyl

transferase (HPRT). This defect is associated withexcessive de novo purine synthesis,

hyperuricemia, and the clinical signs and symptoms

described in the question stem. The biochemicalbasis of the often striking self-mutilatory behavior

(which may require restraints and even tooth

extraction) has never been established. Treatment with

allopurinol inhibits xanthine oxidase andreduces gouty arthritis, urate stone formation, and urate

nephropathy. It does not, however, modify

the neurologic/psychiatric presentation.

An obese individual is brought to the emergency room

by a concerned friend. The patient has been on aself-imposed "starvation diet" for four months, and has

lost 60 pounds while consuming only water

and vitamin pills. If extensive blood studies wereperformed, which of the following would be

expected to be elevated?

A. Acetoacetic acid

B. Alanine

C. Bicarbonate

D. Chylomicrons

E. Glucose

Explanation:

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

energy requirements are normally supplied by serum

glucose, but in starvation are supplied by bothglucose and lipid-derived ketone bodies, including

acetoacetic acid and beta-hydroxybutyric acid.

Glucose cannot be synthesized from lipids, and is

instead made from amino acids such as alanine inthe process of gluconeogenesis.

Serum alanine (choice B) drops dramatically in

starvation, due to its conversion to glucose.

Bicarbonate (choice C) levels drop as the bicarbonate

buffers the hydrogen ions produced by theketone bodies.

Chylomicrons (choice D) are the lipid form seen afterabsorption of dietary fat, and would drop

because the person is not feeding.

Glucose (choice E) is maintained in the blood at a much

lower than normal level during starvation.

A 15-year-old girl is seen by a dermatologist for removal

of multiple squamous cell carcinomas of the


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skin. The patient has nearly white hair, pink irises, very

pale skin, and a history of burning easily

when exposed to the sun. This patient's condition iscaused by a disorder involving which of the

following substances?

A. Aromatic amino acids

B. Branched chain amino acids

C. Glycolipids

D. Glycoproteins

E. Sulfur-containing amino acids

Explanation:

The correct answer is A. The disease is albinism. The

most common form of albinism is caused by a

deficiency of copper-dependent tyrosinase (tyrosinehydroxylase), blocking the production of melanin

from the aromatic amino acid tyrosine. Affected

individuals lack melanin pigment in skin, hair, andeyes, and are prone to develop sun-induced skin

cancers, including both squamous cell carcinomas and

melanomas.

Maple syrup urine disease is an example of a disorder of

branched chain amino acids (choice B)causing motor abnormalities and seizures.

Tay-Sachs disease is an example of a disorder ofglycolipids (choice C). In this disorder, a

deficiency of hexosaminidase A leads to accumulation of

ganglioside GM2.

Hunter's disease is an example of a disorder of

glycoproteins (choice D). This mucopolysaccharidosisis inherited as an autosomal recessive trait.

Homocystinuria disease is an example of a disorder ofsulfur-containing amino acids (choice E).

A 7-year-old boy is referred to a specialty clinic because

of digestive problems. He often experiencessevere abdominal cramps after eating a high fat meal.

He is worked up and diagnosed with a genetic

defect resulting in a deficiency of lipoprotein lipase.Which of the following substances would most

likely be elevated in this patient's plasma following a

fatty meal?

A. Albumin-bound free fatty acids

B. Chylomicrons

C. HDL

D. LDL

E. Unesterified fatty acids

Explanation:

The correct answer is B. After eating a high fat meal,triglycerides are processed by the intestinal

mucosal cells. They are assembled in chylomicrons and

eventually sent into the circulation fordelivery to adipocytes and other cells. Chylomicrons are

too large to enter cells, but are degraded


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while in the circulation by lipoprotein lipase. A defect in

this enzyme would result in the

accumulation of chylomicrons in the plasma.

Albumin-bound free fatty acids (choice A) is incorrect

because fatty acids leave the intestine

esterified as triglycerides in chylomicrons.

HDL (choice C) is not a carrier of dietary fat from the

intestine.

LDL (choice D) would be not be elevated in this patientafter a high fat meal. However, VLDL would

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

be converted into fat in the liver and sent out into

circulation as VLDL. VLDL would be unable to bedegraded to LDL and, therefore, would accumulate.

A defect in lipoprotein lipase would cause a decrease,

not an elevation of unesterified fatty acids(choice E), since the chylomicrons contain esterified

fatty acids.

A 38-year-old man in a rural area presents to a

physician for an employment physical. Ocular

examinationreveals small opaque rings on the lower edge of the iris

in the anterior chamber of the eye. Nodular

lesions are found on his Achilles tendon. Successfultherapy should be aimed at increasing which of

the following gene products in hepatocyte cell

membranes?

A. Apo B-100

B. Apo B-100 receptor

C. Apo E

D. Apo E receptor

E. Lecithin cholesterol acyltransferase

Explanation:

The correct answer is B. This man has characteristic

signs of familial hypercholesterolemia, an

autosomal dominant disorder affecting about 1 in 500persons. The xanthomas on the Achilles tendon

and the arcus lipoides (the opaque rings in the eye) are

pathognomonic. Affected individuals have

very high LDL cholesterol because of deficientendocytosis of LDL particles by LDL receptors. These

receptors recognize the apo B-100 protein cotransported

with cholesterol esters in LDL. Treatments

aim at increasing genetic expression of LDL receptors

(i.e., apo B-100 receptors) to enhanceclearance of LDL particles. Dietary changes, a resin drug,

niacin, or an HMG-CoA reductase inhibitorcould be tried.

Apo B-100 (choice A) is the apoprotein of liver-producedlipoproteins such as VLDL, IDL and LDL. It

is therefore not in the hepatic cell membranes, and it

might be expected to decrease with decreasingconcentrations of circulating LDL.

Apo E (choice C) is an apoprotein found on VLDL, IDL,and chylomicrons, allowing "scavenging" by the

liver of remnants or of the lipoprotein itself. It is not


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found in the hepatocyte membrane.

Apo E receptor (choice D) would actually be increased bythe treatment with hypocholesterolemic

agents. However, the apo E receptor is not involved in

the scavenging of LDL particles.

Lecithin cholesterol acyl transferase (choice E) or LCAT,

is activated by apo AI, and esterifies

free cholesterol in plasma. Plasma levels of HDLcholesterol and apo AI are inversely related to the

risk of coronary heart disease.

Which of the following structures is common to allsphingolipids?

A. Carnitine

B. Ceramide

C. Diacylglycerol

D. Sphingomyelin

E. Squalene

Explanation:

The correct answer is B. Sphingolipids are a class of

lipids that are structural components ofmembranes. Ceramide is a component of sphingolipids.

Ceramide is composed of sphingosine, a long-

chain amino alcohol with a saturated fatty acid linked tothe amino group. Sphingolipids can be

differentiated on the basis of the "X" group that is

esterified to the terminal hydroxyl group ofceramide.

Carnitine (choice A) is involved in the oxidation of fattyacids. Carnitine is important in

transferring fatty acids from the cytoplasm into the

mitochondria (the carnitine shuttle).

Diacylglycerol (choice C) is the alcohol common to all

phospholipids. The second alcohol (e.g.,

choline, ethanolamine, serine) contributes the polarhead that d istinguishes the different classes

of phospholipids. Like sphingolipids, phospholipids are

found in membranes.

Sphingomyelin (choice D) is a sphingolipid with

phosphocholine as its "X" group. It is a component

of the myelin sheath.

Squalene (choice E) is a 30-carbon intermediate in the

synthesis of cholesterol.

A 47-year-old male patient presents with painfularthritis in the right big toe and uric acid renal

stones. He has been taking allopurinol for his condition.What biochemical defect would likely be

found in this patient?

A. A defect in urea synthesis

B. An abnormality of the purine degradation pathway

C. An inability to synthesize non-essential amino acids

D. Defective topoisomerases


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E. Increased levels of leukotrienes

Explanation:

The correct answer is B. This patient has gout,

characterized by painful joints due to the

precipitation of uric acid crystals caused by excessiveproduction of uric acid (a minority of cases

are associated with underexcretion of uric acid). Kidney

disease is also seen due to accumulation ofuric acid in the tubules. The disease mostly affects

males, and is frequently treated withallopurinol, an inhibitor of xanthine oxidase. Xanthine

oxidase catalyzes the sequential oxidationof hypoxanthine to xanthine to uric acid.

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

Phenylketonuria is a disease in which tyrosine cannot be

produced from phenylalanine (choice C). Itis characterized by a musty body odor and mental

retardation.

Defective topoisomerases (choice D) would affect DNA

unwinding, and therefore replication.

Leukotrienes (choice E) are potent constrictors of

smooth muscle and would more likely lead to

bronchoconstriction.

A newborn vomits after each feeding of milk-based

formula, and does not gain weight. Biochemical testingreveals a severe deficiency of galactose-1-phosphate

uridyltransferase, consistent with homozygosity.

If this condition goes untreated, what is the likelyoutcome for this patient?

A. Benign disease except for cataract formation

B. Chronic emphysema appearing in early adulthood

C. Chronic renal failure appearing in adolescence

D. Death in infancy

E. Gastrointestinal symptoms that remit with puberty

Explanation:

The correct answer is D. Galactosemia occurs in two very

different clinical forms. Deficiency of

galactokinase produces very mild disease with the onlysignificant complication being cataract

formation. In contrast, homozygous deficiency of

galactose-1-phosphate uridyltransferase produces

severe disease culminating in death in infancy. In

addition to galactosemia and galactosuria, thesepatients have impaired renal tubular resorption leading

to aminoaciduria, gastrointestinal symptoms,hepatosplenomegaly, cataracts, bleeding diathesis,

hypoglycemia, and mental retardation.

Pathologically, the CNS shows neuronal loss and gliosisand the liver shows fatty change progressing

to cirrhosis.

Benign disease with cataract formation (choice A) is

characteristic of galactokinase deficiency.

Chronic emphysema (choice B) is not associated with

homozygous galactose-1-phosphate


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uridyltransferase deficiency, but rather with alpha

1-antitrypsin deficiency.

Impaired tubular reabsorption (producing

aminoaciduria) is seen within a few days or weeks of

feeding milk to an infant with severe galactosemia, as

opposed to chronic renal failure appearing inadolescence (choice C).

Gastrointestinal symptoms (choice E) certainly occur inhomozygous galactose-1-phosphate

uridyltransferase deficiency, but they would not beexpected to remit with puberty. Instead, most

untreated infants with this disorder show failure tothrive and die in infancy from wasting and

inanition.

A 20-year old female who is 2 months pregnant

remembers that she had phenylketonuria (PKU) as a

child

and required a special diet. Tests confirm markedlyelevated maternal serum levels of phenylalanine

and phenylacetic acid. Genetic studies have not been

performed on the father. What should thephysician tell the parents regarding the welfare of the

child?

A. Childhood phenylalanine restriction is sufficient to

protect the health of her child.

B. Further information is required to ascertain if the

fetus is at risk.

C. The fetus is at no health risk if it is heterozygous for

the PKU gene.

D. The fetus is at no health risk if phenylalanine levels

are normalized by the third trimester.

E. The mother's hyperphenylalaninemia may have

already harmed the fetus.

Explanation:

The correct answer is E. Phenylalanine crosses the

placenta and, if maternal serum levels areelevated, acts as a teratogen to the developing fetus.

This condition is known as maternal PKU.

Although the mother can fare well with substantialelevations in serum phenylalanine concentration,

the children born to such women are usually profoundly

retarded and may have multiple b irth defects.

Although dietary modifications (choice A) can prevent

the neurological and dermatologic

manifestations of PKU in a child, the fetus is still at risk

from maternal PKU.

Further information regarding the cause of this woman's

hyperphenylalaninemia (choice B) is notneeded, since the fetus is exposed to teratogenic levels

of phenylalanine.

Children born to mothers with untreated PKU develop

maternal PKU even if they are heterozygous for

the PKU gene (choice C). Fetal phenylalaninehydroxylase cannot compensate for the high maternal

levels of phenylalanine.

The critical period in development during which

teratogenic materials affect the growing organs is


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between the 3rd and 8th weeks of gestation. By the end

of the 2nd month (compare with choice D), the

damage caused by the maternal PKU has alreadyoccurred.

A 24-year-old graduate student presents to a physician

with complaints of severe muscle cramps andweakness with even mild exercise. Muscle biopsy

demonstrates glycogen accumulation, but hepatic

biopsy is unremarkable. Which of the following is themost likely diagnosis?

A. Hartnup's disease

B. Krabbe's disease

C. McArdle's disease

D. Niemann-Pick disease

E. Von Gierke's disease

Explanation:

The correct answer is C. A variety of glycogen storage

diseases exist, corresponding to defects in

different enzymes in glycogen metabolism; most ofthese involve the liver. McArdle's disease (Type V

glycogen storage disease), due to a defect in muscle

phosphorylase, is restricted to skeletalmuscle. The presentation described in the question stem

is typical. Many affected individuals also

experience myoglobinuria. Definitive diagnosis is basedon demonstration of myophosphorylase

deficiency.

Hartnup's disease (choice A) is a disorder of amino acid

transport.

Krabbe's disease (choice B) is a lysosomal storage

disease.

Niemann-Pick disease (choice D) is a lysosomal storage

disease.

Von Gierke's disease (choice E) is a glycogen storagedisease with prominent involvement of liver,

intestine, and kidney.

Which of the following metabolic processes occurs

exclusively in the mitochondria?

A. Cholesterol synthesis

B. Fatty acid synthesis

C. Gluconeogenesis

D. Glycolysis

E. Hexose monophosphate shunt

F. Ketone body synthesis

G. Urea cycle

Explanation:

The correct answer is F. Of the processes listed, onlyketone body synthesis occurs exclusively in

the mitochondria. Other mitochondrial processes include


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the production of acetyl-CoA, the TCA cycle,

the electron transport chain, and fatty acid oxidation.

Processes that occur exclusively in the cytoplasm include

cholesterol synthesis (choice A; in

cytosol or in ER), fatty acid synthesis (choice B),

glycolysis (choice D), and the hexosemonophosphate shunt (choice E).

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

and the cytoplasm.

A physician from the United States decides to take asabbatical from his responsibilities at a teaching

hospital to work in a clinic in a remote part of Africa.

During his first week at the clinic, he istold that he will be seeing a patient with g lucose-

6-phosphate dehydrogenase deficiency. Which of the

following will be the most likely clinical presentation of

this patient?

A. A 6-month-old child who develops severe anemia

following a respiratory tract infection

B. A child who develops hemoglobinuria following a meal

of beans

C. A neonate with an enlarged spleen and severe anemia

D. An adult who develops anemia following use of

antimalarial drugs

E. An adult who develops severe shortness of breath

during an airplane ride

Explanation:

The correct answer is B. In Africa, the classicpresentation of glucose-6-phosphate dehydrogenase

deficiency is a child who eats a meal of beans (Vicia

fava) and several hours later developshemoglobinuria and peripheral vascular collapse

secondary to intravascular hemolysis as a result of

the oxidant injury initiated by the fava beans. Blood

studies in this setting show a rapid fall intotal hemoglobin and a rise in free plasma hemoglobin,

accompanied by a rise in unconjugated

bilirubin and a fall in haptoglobin. The episode usuallyresolves spontaneously several days later.

Today, the classic presentation is less common in

developed countries than is a slower onset

syndrome beginning 1-3 days after starting anantimalarial drug, sulfonamide, or other antioxidant

drug. Rarely, glucose-6-phosphate dehydrogenase

deficiency presents as neonatal jaundice or with

chronic hemolysis.

A patient with familial hypercholesterolemia undergoes a

detailed serum lipid and lipoprotein analysis.Studies demonstrate elevated cholesterol in the form of

increased LDL without elevation of other

lipids. This patient's hyperlipidemia is best classified aswhich of the following types?

A. Type 1

B. Type 2a

C. Type 2b


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D. Type 3

E. Type 5

Explanation:

The correct answer is B. Hyperlipidemia has beensubclassified based on the lipid and lipoprotein

profiles. Type 2a, which this patient has, can be seen in

a hereditary form, known as familialhypercholesterolemia, and also in secondary, acquired

forms related to nephritic syndrome andhyperthyroidism. The root problem appears to be a

deficiency of LDL receptors, which leads to aspecific elevation of cholesterol in the form of increased

LDL. Heterozygotes for the hereditary

form generally develop cardiovascular disease from 30 to50 years of age. Homozygotes may have

cardiovascular disease in childhood.

Type 1 (choice A) is characterized by isolated elevationof chylomicrons.

Type 2b (choice C) is characterized by elevations of bothcholesterol and triglycerides in the form

of LDL and VLDL.

Type 3 (choice D) is characterized by elevations of

triglycerides and cholesterol in the form of

chylomicron remnants and IDL.

Type 5 (choice E) is characterized by elevations of

triglycerides and cholesterol in the form ofVLDL and chylomicrons.

During the isolation of Met-enkephalin (Tyr-Gly-Gly-Phe-Met) from post-mortem human brain tissue,

researchers find that the peptide is rapidly degraded by

peptidases in 1 minute at 37 C. Detailedanalysis of the peptide cleavage pattern of

Met-enkephalin is investigated with two candidate

enzymes. Using the drug bestatin, the investigatorsfound no detectable Tyr-Gly-Gly-Phe-Met but did

find significant concentrations of Tyr-Gly-Gly. Using

thiorphan, there was no detectable Tyr-Gly-

Gly-Phe-Met, but there was a high concentration of Tyr.Which of the following is the best

conclusion about Met-enkephalin metabolism that can

be drawn from these data?

A. Bestatin inhibits an aminopeptidase, and thiorphan

inhibits an endopeptidase in the degradative

pathway

B. Bestatin inhibits a carboxypeptidase in the

degradative pathway

C. Bestatin inhibits an endopeptidase in the degradativepathway

D. Thiorphan inhibits an aminopeptidase, and bestatin

inhibits an endopeptidase in the degradative

pathway

E. Thiorphan inhibits an aminopeptidase in the

degradative pathway

Explanation:

The correct answer is A. Met-enkephalin, the most

abundant opioid peptide in the human brain, undergoes


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two routes of metabolism. One route releases a

tripeptide and therefore is the result of a peptidase

that cuts an amino acid bond within the molecule: anendopeptidase. The other route releases free

tyrosine and therefore is an exopeptidase. Exopeptidases

can remove amino acid residues from the amino-

or carboxyl-terminus of the protein. By convention, allpeptide sequences are given from the N to the C

terminus, the direction of translation. Tyrosine is

therefore at the amino-terminus of Met-enkephalin,and its release is the result of digestion by an

aminopeptidase.

The scientists have used two drugs to highlight the twoenzymatic pathways. With bestatin, Met-

enkephalin is metabolized only to the tripeptide;

therefore bestatin inhibits the aminopeptidaseenzyme, preventing release of free tyrosine residues.

With thiorphan, Met-enkephalin is metabolized to

free tyrosine; the tripeptide is no longer formed.

Thiorphan is an inhibitor of the endopeptidase. Thelack of persistence of Met-enkephalin in the presence of

an enzyme inhibitor is evidence that the

peptide's metabolism is shifted in the direction of thenoninhibited enzyme. A schematic of the

metabolism would be:

Tyrosine cannot be the result of carboxypeptidase

activity (choice B), since the carboxyl-terminus of

Met-enkephalin is a methionine.

Bestatin inhibits an aminopeptidase, not an

endopeptidase (choice C). An endopeptidase would notrelease a free amino acid residue.

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

inhibits

the aminopeptidase and thiorphan inhibits theendopeptidase (compare with choice D).

Thiorphan does not inhibit an aminopeptidase (choiceE); furthermore, such an enzyme would release a

free Tyr and a tetrapeptide.

The parents of a 6-month-old child who was normal atbirth bring her into the clinic. Since their

emigration to the U.S. from Eastern Europe soon after

her birth, the child has developed diminishedresponsiveness, progressive blindness and deafness, and

recently, seizures. Serum levels of which of

the following compounds would be expected to be

decreased in both of the parents?

A. Dystrophin

B. Hexosaminidase A

C. Hypoxanthine-guanine phosphoribosyltransferase

(HGPRT)

D. Phenylalanine hydroxylase

E. Vitamin D3

Explanation:

The correct answer is B. This patient has Tay-Sachs

disease, an autosomal recessive disorder causedby the deficiency of hexosaminidase A, which leads to

the accumulation of ganglioside GM2 in neurons,


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producing a degenerative neurologic disease. Children

appear normal at birth, but then begin to

suffer from diminished responsiveness, deafness,blindness, loss of neurologic function, and

seizures. A cherry-red spot on the macula may be seen

by ophthalmoscopic examination. Death usually

occurs by 4 to 5 years of age. There is no therapy. Theincidence is higher among Jews of Eastern

European descent. Since the parents must be

heterozygotes for the mutant hexosaminidase A allele,they would be expected to have diminished levels of the

enzyme.

A defect in the dystrophin (choice A) gene producesDuchenne muscular dystrophy, characterized by

onset of weakness in early childhood.

A severe deficiency in HGPRT (choice C) will lead to

Lesch-Nyhan syndrome, characterized by excessive

uric acid production, mental retardation, spasticity,

self-mutilation, and aggressive, destructivebehavior.

Deficiency of phenylalanine hydroxylase (choice D)results in classic phenylketonuria, a disease in

which phenylalanine, phenylpyruvate, phenylacetate,

and phenyllactate accumulate in plasma and urine.Clinically, there is a musty body odor and mental

retardation.

Hypophosphatemic rickets is an X-linked dominant

condition causing abnormal regulation of vitamin D3

(choice E) metabolism and defects in renal tubularphosphate transport. Symptoms include growth

retardation, osteomalacia, and rickets.

Poor oxygenation of tissues decreases the production of

ATP necessary for many cellular functions. Which

of the following processes is most immediatelycompromised in a typical cell when ATP production is

inadequate?

A. Complex carbohydrate synthesis

B. Lipid synthesis

C. Na+/K+ ATPase function

D. Nucleic acid synthesis

E. Protein synthesis

Explanation:

The correct answer is C. While ATP is important in

cellular synthetic functions, its role in

maintaining the Na+/ K+ exchange across the

plasmalemma is actually the most immediatelyimportant

function for most cells. The direct effect of this is theenergy (ATP) driven exchange of 3 Na+ ions

(which go from inside the cell to outside) for 2 K+ ions

(which go from outside to inside). Thisprocess requires considerable energy (1 ATP per

3Na+/2K+ exchange), since both the Na+ and K+ are

traveling against a concentration gradient. This directeffect of the Na+/ K+ ATPase may seem

trivial, but the secondary consequences are dramatic.

The Na+/ K+ ATPase helps establish thetransmembrane potential of the cell (because the

quantitatively uneven exchange of Na+/ K+ drives


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more positive ions out of the cell than in) and also both

the Na+ and K+ gradients. All of these

facilitate a wide variety of exchanges andtransmembrane transport systems that allow entry into

the

cell of the large variety of small molecules and ions that

it needs. The first microscopicallyvisible effect of significant hypoxia is cellular edema,

which is a consequence of distorted water

balance, also an indirect function of the Na+/ K+ATPase.

Urine screening of an apparently healthy pregnant

woman demonstrates a positive Clinitest reaction.However, blood glucose levels were within normal limits,

and more specific testing for urine glucose

is negative. The woman has been unaware of anymetabolic problems and has been living a normal life.

Deficiency of which of the following enzymes would most

likely produce this presentation?

A. Fructokinase

B. Fructose 1-phosphate aldolase

C. Galactose 1-P-uridyl transferase

D. Lactase

E. Pyruvate dehydrogenase

Explanation:

The correct answer is A. Glucose, galactose, and fructose

are all reducing sugars, and elevations of

all of these sugars can be detected with Clinitest tablets.Neither lactose nor pyruvate can be

detected, thus eliminating lactase and pyruvate

dehydrogenase as plausible choices. This leavesthree possibilities: fructokinase, fructose 1-phosphate

aldolase, and galactose 1-P-uridyl

transferases. Of these, only fructokinase deficiencyproduces a mild (usually completely

asymptomatic) condition known as fructosuria.

Fructose 1-phosphate aldolase deficiency (choice B)produces severe hereditary fructose intolerance.

Galactose 1-P-uridyl transferase deficiency (choice C)produces classic galactosemia.

Lactase deficiency (choice D) produces lactose

intolerance.

Pyruvate dehydrogenase deficiency (choice E) produces

severe disease (e.g., a subset of Leigh's

disease).

Addition of which of the following exhaustively 14C

labeled substrates would lead to evolution of 14CO2from a cell-free suspension containing all the enzymes

and substrates required for the synthesis of

uridylic acid?

A. Aspartate

B. Carbamoyl phosphate

C. Glutamine

D. Glycine


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E. N10-Formyltetrahydrofolate

Explanation:

The correct answer is A. In the first step of pyrimidinesynthesis, carbamoyl phosphate condenses

with aspartate to form carbamoyl aspartate, in a reaction

catalyzed by aspartate transcarbamoylase.

In subsequent steps, ring closure occurs with the loss ofwater, followed by oxidation to yield

orotic acid. Addition of ribose-5-phosphate producesorotidylic acid, which is decarboxylated by

orotidylate decarboxylase to yield uridylic acid. Thecarbon dioxide that is evolved is derived from

the alpha carboxyl group of aspartate.

Carbamoyl phosphate (choice B) condenses with

aspartate with the loss of inorganic phosphate to

produce carbamoyl aspartate. The carbamoyl moiety of

carbamoyl phosphate is retained.

Glutamine (choice C), glycine (choice D) and

N10-formyltetrahydrofolate (choice E) are all used inpurine synthesis. Glutamine also donates an amino

group to UTP to form CTP, but this step occurs

after the synthesis of uridylic acid is complete.

A histological section of the left ventricle of a deceased

28-year-old white male shows classiccontraction band necrosis of the myocardium. Biological

specimens confirm the presence of cocaine and

metabolites. Activity of which of the following enzymeswas most likely increased in the patient's

myocardial cells shortly prior to his death?

A. Phosphoenolpyruvate carboxykinase

B. Phosphofructokinase-1

C. Pyruvate dehydrogenase

D. Succinate dehydrogenase

E. Transketolase

Explanation:

The correct answer is B. Cocaine causes contractionband necrosis by blocking the reuptake of

norepinephrine, resulting in excessive vasoconstriction

of coronary vessels, leading to ischemia and

infarction of heart tissue. Under these pathologicalconditions, myocardial cells switch to anaerobic

metabolism and therefore glycolysis becomes the sole

source of ATP via substrate-level

phosphorylations by phosphoglycerate kinase and

pyruvate kinase. Phosphofructokinase-1 (PFK-1) is therate-limiting enzyme of glycolysis, and its activity would

therefore be increased.

Phosphoenolpyruvate carboxykinase (choice A) is a

regulatory enzyme in gluconeogenesis, which isinduced by cortisol, epinephrine, and glucagon. It

functions in the hepatic synthesis of glucose when

energy levels from beta-oxidation of fatty acids areadequate.

Pyruvate dehydrogenase (choice C) produces acetyl-CoAfrom pyruvate and coenzyme A, bridging

glycolysis and the Krebs cycle. It requires 5 cofactors,


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including NAD and FAD, which would no longer

be produced by the electron transport under hypoxic

conditions, decreasing its activity.

Succinate dehydrogenase (choice D) is a key enzyme of

the Krebs cycle, producing a reduced equivalent

of FAD to feed into the electron transport chain. It isalso known as Complex II. The Krebs cycle

only functions if oxygen is in appropriate concentrations

since it is regulated by the levels ofNADH, which is only consumed by the electron transport

chain if there is enough oxygen. The absenceof oxygen leads to an accumulation of NADH and a

subsequent decrease in the enzyme activities of theKrebs cycle.

Transketolase (choice E) is a thiamine requiring enzymeof the non-oxidative half of the hexose

monophosphate shunt. The shuffling of sugars in the

second half of this pathway results in the

reentry of glyceraldehyde-3-phosphate and fructose-6-phosphate into the glycolytic pathway.

Transketolase activity in red blood cells is used as a

clinical marker of thiamine deficiency,markedly decreasing in disorders such as Wernicke-

Korsakoff syndrome.

An 8-month-old child is brought to a pediatrician

because of the mother's concern about the boy's

tendency to compulsively bite his fingers. Onquestioning, the mother reported that she has noticed

yellow-orange crystals in his diapers, but has not

mentioned them to anyone. A genetic defect inwhich of the following pathways should be suspected?

A. Aromatic amino acid metabolism

B. Branched chain amino acid metabolism

C. Purine metabolism

D. Pyrimidine metabolism

E. Sulfur-containing amino acid metabolism

Explanation:

The correct answer is C. The disease is Lesch-Nyhan

syndrome, and the yellow-orange crystals of uricacid in the diaper are an important, but often neglected,

clue to early diagnosis. Lesch-Nyhan

syndrome is characterized by a tremendous

overproduction of purines, because the reutilization ofpurines via the purine salvage pathway is blocked by a

near total absence of hypoxanthine-guanine

phosphoribosyl-transferase (HGPRT) activity. Patients

with this severe X-linked disease, for reasons

that are unknown, show aggressive behavior that leadsto self-mutilation. They may also develop

gouty arthritis or gouty nephropathy.

Phenylketonuria is an example of a disorder of aromatic

amino acid metabolism (choice A)characterized by mental retardation.

Maple syrup urine disease is an example of a disorder ofbranched chain amino acids (choice B)

causing motor abnormalities and seizures.

Orotic aciduria is an example of a disorder of pyrimidine

metabolism (choice D), characterized by


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retarded growth and development as well as

megaloblastic anemia.

Homocystinuria is an example of a disorder of sulfur-

containing amino acids (choice E),

characterized by mental retardation, dislocation of the

lenses, osteoporosis, and thromboses.

Which of the following will be unchanged in a

Lineweaver-Burk plot of an enzyme with and without acompetitive inhibitor?

A. Km

B. Slope

C. x-intercept

D. y-intercept

Explanation:

The correct answer is D. It is worth taking the time to

learn how to read a Lineweaver-Burk plot.Lineweaver-Burk plots are used to determine the Vmax

and Km of an enzyme; they are also used to

differentiate between competitive and noncompetitiveinhibition.

Note that in a Lineweaver-Burk plot, the slope isKm/Vmax, the x-intercept is -1/Km, and the y-

intercept is 1/Vmax. In the presence of a competitive

inhibitor, the Km(choice A) and therefore theslope (choice B) are both increased. Similarly, if Km is

increased, -1/Km will become less negative

and the x-intercept will shift to the right. Intuitively,this makes sense since a competitive

inhibitor will increase the amount of substrate needed to

reach half-maximal velocity (definition ofKm). In contrast, the Vmax, and hence the y-intercept,

is unchanged (choice D).

Which of the following metabolic alterations would most

likely be present in a chronic alcoholic

compared to a non-drinker?

A. Fatty acid oxidation is stimulated

B. Gluconeogenesis is stimulated

C. Glycerophosphate dehydrogenase is stimulated

D. The ratio of lactate to pyruvate is decreased

E. The ratio of NADH to NAD+ is increased

Explanation:

The correct answer is E. The principal route of

metabolism of ethanol is via alcohol dehydrogenase,which uses hydrogen from ethanol to form NADH from

NAD+, markedly increasing the ratio of NADH to

NAD+. The relative excess of NADH has a number ofeffects, including inhibiting, rather than

stimulating fatty acid oxidation (choice A); inhibiting

gluconeogenesis rather than stimulating it(choice B); inhibiting, rather than stimulating (choice C)

glycerophosphate dehydrogenase; and

favoring the formation of lactate rather than pyruvatefrom glycolysis (thereby increasing, rather

than decreasing the lactate/pyruvate ratio; choice D).


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A couple brings in their 6-month-old child because they

are concerned about the child's inability to sitwithout support. The physician interviews the parents

and ascertains that they are both Ashkenazic

Jews. The doctor should inform them that, because oftheir heritage, their child may have an

increased risk of which of the following disorders?

A. Albinism and galactosemia

B. Cystic fibrosis and Lesch-Nyhan disease

C. Gaucher's disease and Tay-Sachs disease

D. Krabbe's disease and Niemann-Pick disease

E. Metachromatic leukodystrophy and phenylketonuria

Explanation:

The correct answer is C. You should associate Ashkenazic

(Eastern European) Jews with two diseases:

Tay-Sachs disease and Type I Gaucher's disease. Both ofthese diseases are sphingolipidoses. Tay-

Sachs disease is the more devastating of the two, and is

characterized by progressive neurologic(including visual) deterioration beginning at about 6

months of age and leading to death by age 3.

In contrast, Type I Gaucher's disease is compatible witha normal life span and causes

hepatosplenomegaly with CNS involvement. (The

infantile Type II and the juvenile Type III formscause more serious disease but are not seen with

increased incidence in Ashkenazic Jews.) None of

the other conditions listed occur with greater frequencyin Ashkenazic Jews. In this case, also note

that many perfectly normal children cannot sit without

support at 6 months of age, so the child maywell be healthy.

A 2-year-old retarded child is evaluated by a metabolicspecialist. The child's history is significant

for failure to thrive and progressive neurologic

deterioration, including deafness and blindness.

Physical examination is remarkable forhepatosplenomegaly, as well as a cherry-red spot on

funduscopic examination. These symptoms are

consistent with a diagnosis of

A. Hunter syndrome

B. Niemann-Pick disease

C. Pompe's disease

D. tyrosinosis

E. von Gierke's disease

Explanation:

The correct answer is B. Hepatosplenomegalyaccompanied by progressive neurologic deterioration

should make you think of lipid storage diseases;

Niemann-Pick disease is the only lipid storagedisease in the answer choices. Niemann-Pick disease is

due to a deficiency of sphingomyelinase,

leading to an accumulation of sphingomyelin. It is mostcommon among Ashkenazic Jews and generally

results in death by age 2. The cherry-red spot is also a


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characteristic of Tay-Sachs disease, but

hepatosplenomegaly suggests Niemann-Pick disease

rather than Tay-Sachs.

Hunter syndrome (choice A) is a mucopolysaccharidosis,

inherited in an X-linked recessive fashion.

Pompe's disease (choice C) is a glycogen storage

disease characterized by hypotonia and

cardiorespiratory failure.

Tyrosinosis (choice D) is a rare abnormality of tyrosinemetabolism that would not produce the

listed symptoms.

von Gierke's disease (choice E) is a severe form of

glycogen storage disease characterized byhypoglycemia, hepatomegaly, and renomegaly.

26

Which of the following enzymes is located at arrow 1 in

the electron micrograph above?

A. Carnitine acyltransferase II

B. Fatty acyl CoA synthetase

C. Glucose-6-phosphate dehydrogenase

D. Hexokinase

E. Pyruvate kinase

Explanation:

The correct answer is A. Arrow 1 indicates the inner

mitochondrial membrane. Carnitine acyltransferase

II is located on the inner face of the inner mitochondrialmembrane. It reforms fatty acyl CoA in the

mitochondrial matrix (arrow 5) from acyl carnitine, thus

preparing it for mitochondrial oxidation. Theacyl groups on carnitine are derived from acyl CoA esters

synthesized in the outer mitochondrial

membrane, which are made from free fatty acids

circulating in the blood.

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

outer mitochondrial membrane, indicated byarrow 2.

Glucose-6-phosphate dehydrogenase, the first enzyme

in the pentose phosphate pathway (choice C),hexokinase, the first enzyme in the glycolytic pathway

(choice D), and pyruvate kinase (choice E),

which produces pyruvate from phosphoenolpyruvate in

glycolysis, are all located in the cytosol,

indicated by arrow 3.

Arrow 4 indicates smooth endoplasmic reticulum.

A 72-year-old woman, in otherwise good health,

presents with megaloblastic anemia. Careful evaluationreveals a folate deficiency as the cause of the anemia.

Assuming the folate deficiency is due to

dietary causes, which of the following is the most likelyproblem?

A. Lack of leafy green vegetables

B. Lack of milk products


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C. Lack of red meat

D. Lack of yellow vegetables

E. Overcooked food

Explanation:

The correct answer is E. Folates (pteroylglutamic acidand related compounds) are widely distributed

in foodstuffs. Dietary deficiency is usually due toovercooked (folates are very labile) and old

(folates rapidly decay with time) food.

A 2-month-old boy is evaluated for failure to thrive. As

the pediatrician is examining the patient, shewitnesses a seizure. Physical examination is remarkable

for hepatomegaly, a finding later confirmed

by CT scan, which also reveals renomegaly. Serum

chemistries demonstrate severe hypoglycemia,hyperlipidemia, lactic acidosis, and ketosis. Which of the

following diseases best accounts for this

presentation?

A. Gaucher's disease

B. McArdle's disease

C. Niemann-Pick disease

D. Pompe's disease

E. von Gierke's disease

Explanation:

The correct answer is E. von Gierke's disease is a

glycogen storage disease caused by a deficiencyof glucose-6-phosphatase. It typically presents with

neonatal hypoglycemia, hyperlipidemia, lactic

acidosis, and ketosis. Failure to thrive is common inearly life; convulsions may occur due to

profound hypoglycemia. The glycogen accumulation in

von Gierke's disease occurs primarily in the

liver and kidneys, accounting for the enlargement ofthese organs. Gout may develop later because of

the derangement of glucose metabolism.

Even if you do not remember all of the details of the

presentation of these genetic diseases, you

should be able to narrow the choices:

Gaucher's disease (choice A) and Niemann-Pick disease

(choice C) are lipid storage diseases, and

would not be expected to produce hypoglycemia.

The other diseases are glycogen storage diseases, butMcArdle's (choice B) and Pompe's (choice D)

disease affect muscle rather than liver and would not beexpected to produce profound hypoglycemia,

since the liver is the major source for blood glucose.

A newborn appears normal at birth, but develops

vomiting and diarrhea accompanied by jaundice and

hepatomegaly within the first few weeks of life. Withinmonths, the baby has obvious cataracts and

ascites. The infant is switched to a milk-free diet, which

stabilizes but does not completely reversehis condition. By one year of age, he has developed

mental retardation. Which of the following is the


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most likely diagnosis?

A. Cystic fibrosis

B. Galactosemia

C. McArdle's disease

D. Von Gierke's disease

E. Wilson's disease

Explanation:

The correct answer is B. Galactosemia is an autosomal

recessive disease caused by a deficiency of

galactose-1-phosphate uridyltransferase, which isnecessary for the metabolism of the galactose

derived from milk lactose. The condition should be

suspected in infants with growth failure,

cataracts, liver disease, aminoaciduria, and mentalretardation. A reducing sugar (galactose) is

usually present in the urine. Most of the pathology is

related to the toxic effects of galactose-1-phosphate. Treatment involves strict dietary lactose

restriction, which consists of more than simply

withdrawal of milk products, because lactose is alsopresent in many non-diary foods. Strict

adherence to the diet can strikingly alter the course of

this disease.

Cystic fibrosis (choice A) is associated with

maldigestion, pancreatic disease, and pulmonarydisease.

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

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

Wilson's disease (choice E) is a caused by a metabolicabnormality in the handling of copper that

can cause cirrhosis and brain damage, and usually

presents in adolescence.

Which of the following pairs of enzymes is required for

the process of gluconeogenesis?

A. Fructose-1,6-bisphosphatase and pyruvate

carboxylase

B. Glucose-6-phosphatase and phosphofructokinase-1

C. Glucose-6-phosphatase and pyruvate dehydrogenase

D. Phosphoenolpyruvate carboxykinase and glucokinase

E. Pyruvate kinase and pyruvate carboxylase

Explanation:

The correct answer is A.The three irreversible steps ofglycolysis are catalyzed by hexokinase,

phosphofructokinase-1 (choice B), and pyruvate kinase.

In gluconeogenesis, other enzymes are neededto bypass these key steps. Pyruvate cannot be directly

converted to phosphoenolpyruvate in

gluconeogenesis. Therefore, pyruvate carboxylase (amitochondrial enzyme; choice A) converts pyruvate

to oxaloacetate, which can be converted to


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phosphoenolpyruvate by phosphoenolpyruvate

carboxykinase

(choice D), using two ATP equivalents per molecule ofphosphoenolpyruvate. Fructose-1,6-

bisphosphatase (choice A) is the enzyme that splits

fructose-1,6-bisphosphate into fructose-6-

phosphate and inorganic phosphate. It is also requiredfor gluconeogenesis.

Glucose-6-phosphatase (choices B and C) is a liverenzyme that hydrolyzes glucose-6-phosphate to

glucose. A deficiency of this enzyme leads to von Gierkedisease, also known as glycogen storage

disease type I.

Pyruvate dehydrogenase (choice C) is a mitochondrial

enzyme that converts pyruvate to acetyl CoA.This enzyme requires thiamine pyrophosphate,

lipoamide, and FAD as cofactors.

Glucokinase (choice D) is a liver enzyme that convertsglucose to glucose-6-phosphate. Unlike

hexokinase, it is specific for glucose and is unresponsive

to the level of glucose-6-phosphate. Itsfunction is to store excess glucose, so it has a very high

Km (ie, a low affinity) for glucose,

becoming active only when the concentration of glucoseis very high.

Pyruvate kinase (choice E) catalyzes the conversion ofphosphoenolpyruvate to pyruvate in the

glycolytic pathway. It is activated by fructose-

1,6-bisphosphate, the product of the committed stepof glycolysis, and is allosterically inhibited by ATP,

alanine, and acetyl CoA.

A 40-year-old, formerly obese woman presents to her

physician. She was very proud of having lost 80 lbs.

during the previous 2 years, but now noticed that her"hair is falling out." On questioning, she

reports having followed a strict fat-free diet. Her

alopecia is probably related to a deficiency ofwhich of the following vitamins?

A. Vitamin A

B. Vitamin C

C. Vitamin D

D. Vitamin E

E. Vitamin K

Explanation:

The correct answer is A. While it is hard to develop a

deficiency in oil-soluble vitamins (A, D, E,K) because the liver stores these substances, deficiency

states can be seen in chronic malnutrition(specifically chronic fat deprivation) and chronic

malabsorption. Vitamin A is necessary for

formation of retinal pigments (deficiency can causenight blindness) and for appropriate

differentiation of epithelial tissues (including hair

follicles, mucous membranes, skin, bone, andadrenal cortex).

Vitamin C (choice B), which is water soluble rather thanoil soluble, is necessary for collagen

synthesis.


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Vitamin D (choice C) is important in calcium absorption

and metabolism.

Vitamin E (choice D) is a lipid antioxidant that is

important in the stabilization of cellmembranes.

Vitamin K (choice E) is necessary for normal blood

coagulation.

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

and contains 200,000 WBC/mm3 (85% neutrophils).Needle-shaped, strongly negatively birefringent

crystals are seen both within and outside neutrophils.

These crystals most likely have which of thefollowing compositions?

A. Basic calcium phosphate

B. Calcium oxalate

C. Calcium pyrophosphate dihydrate

D. Cholesterol

E. Monosodium urate

Explanation:

The correct answer is E. All the compounds listed can

produce crystals in joint fluid, but onlymonosodium urate (associated with gout) and calcium

pyrophosphate dihydrate (associated with CPPD

crystal deposition disease, also called pseudogout), andto lesser degree basic calcium phosphate

(apatite-associated arthropathy), have a high likelihood

of being encountered on a step 1 USMLEexam. The crystals described are those of monosodium

urate. Be careful not to answer "uric acid" if

that is listed as an alternative choice on an exam, sincethe sodium salt is the predominant species

in vivo.

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

clumps of nonbirefringent submicroscopic crystals.

Calcium oxalate crystals (choice B) are seen in primary

oxalosis and are bipyramidal, positively

birefringent crystals.

Calcium pyrophosphate dihydrate crystals (choice C) are

a feature of pseudogout and are rod-to-

rhomboidal-shaped, weakly positively birefringent

crystals.

Cholesterol crystals (choice D) are seen in chronic and

chylous effusions in inflammatory anddegenerative arthritis, where they form large, flat,

rhomboidal plates with notched corners.

Which of the following cofactors is required for

decarboxylation of alpha-ketoacids?

A. Vitamin B1

B. Vitamin B2

C. Vitamin B3


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D. Vitamin B5

E. Vitamin B6

Explanation:

The correct answer is A. Vitamin B1, or thiamine, is the

coenzyme required (as the pyrophosphate)

for the decarboxylation of alpha-ketoacids. An exampleof this reaction is pyruvate decarboxylase

reaction in alcoholic fermentation. Other reactions suchas that catalyzed by pyruvate dehydrogenase

also rely on thiamine pyrophosphate for decarboxylation,but require other cofactors as well.

Thiamine is also required for the generation of pentose

phosphates for nucleotide synthesis in thepentose phosphate pathway (hexose monophosphate

shunt), serving as a cofactor for transketolase.

Vitamin B2(choice B), or riboflavin, is a constituent ofFMN (flavin mononucleotide) and FAD (flavin

adenine dinucleotide). It functions in hydrogen and

electron transport.

Vitamin B3(choice C), or niacin (nicotinic acid), is a

coenzyme that is also involved in hydrogenand electron transport. Nicotinic acid functions in the

form of NAD and NADP.

Vitamin B5(choice D), or pantothenic acid, is conjugated

with coenzyme A to act as a carboxylic acid

carrier.

Vitamin B6(choice E), or pyridoxine, is required as a

cofactor for pyridoxal phosphate andpyridoxamine phosphate. Both of these cofactors are

essential to protein metabolism and energy

production.

A newborn presents with severe acidosis, vomiting,

hypotonia, and neurologic deficits. Serum analysisreveals elevated levels of lactate and alanine. These

observations suggest a deficiency in which of

the following enzymes?

A. Alanine aminotransferase

B. Glutamate dehydrogenase

C. Lactate dehydrogenase

D. Pyruvate carboxylase

E. Pyruvate dehydrogenase

Explanation:

The correct answer is E. Pyruvate dehydrogenase (PDH)

catalyzes the irreversible conversion ofpyruvate to acetyl-CoA. If PDH is absent, pyruvate will

be used in other pathways instead. Pyruvate

will be converted to alanine via alanine aminotransferase(choice A) and to lactate via lactate

dehydrogenase (choice C).

Glutamate dehydrogenase (choice B) is involved in

oxidative deamination, releasing ammonium ion for

urea synthesis. Deficiency of this enzyme would notcause the symptoms described.


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Pyruvate carboxylase (choice D) is a gluconeogenic

enzyme that catalyzes the conversion of pyruvate

to oxaloacetate. Deficiency of this enzyme would notcause the symptoms described.

The activity of which of the following enzymes is directly

affected by citrate?

A. Fructose-2,6-bisphosphatase

B. Isocitrate dehydrogenase

C. Phosphofructokinase I

D. Pyruvate carboxylase

E. 6-phosphogluconate dehydrogenase

Explanation:

The correct answer is C. Citrate is produced by citratesynthase from acetyl CoA and oxaloacetate.

This reaction takes place in the mitochondria, but citrate

can move freely from the mitochondria intothe cytosol. When the citric acid cycle slows down,

citrate accumulates. In the cytosol, it acts as a

negative allosteric regulator of phosphofructokinase I,the enzyme that catalyzes the committed step

of glycolysis.

Fructose-2,6-bisphosphatase (choice A) breaks down

fructose-2,6-bisphosphate, a potent allosteric

activator of phosphofructokinase I. Fructose-2,6-bisphosphatase is activated by cyclic

AMP-dependent

protein kinase.

Isocitrate dehydrogenase (choice B) converts isocitrate

to alpha-ketoglutarate in the citric acidcycle. It is allosterically stimulated by ADP and inhibited

by ATP and NADH. This reaction produces

NADH and CO2.

Pyruvate carboxylase (choice D) is a mitochondrial

enzyme that converts pyruvate to oxaloacetate. It

is important in gluconeogenesis and replenishes theoxaloacetate in the citric acid cycle.

6-phosphogluconate dehydrogenase (choice E) converts6-phosphogluconate to ribulose 5-phosphate in

the pentose phosphate shunt pathway.

Which of the following enzymes is stimulated byglucagon?

A. Acetyl-CoA carboxylase

B. Glycogen phosphorylase

C. Glycogen synthase

D. HMG-CoA reductase

E. Pyruvate kinase

Explanation:

The correct answer is B. Before you started analyzing all

of the answer choices you should havereminded yourself that glucagon increases serum

glucose. So an enzyme stimulated by glucagon might


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be involved in either the breakdown of glycogen to

glucose (glycogenolysis) or in the creation of

glucose from noncarbohydrate precursors(gluconeogenesis). Glycogen phosphorylase catalyzes

the

first step in glycogenolysis; it makes sense that it would

be stimulated by glucagon.

Acetyl-CoA carboxylase (choice A) catalyzes the first

step in fatty acid synthesis, an anabolicprocess that would be stimulated by insulin, not

glucagon.

As its name implies, glycogen synthase (choice C) isinvolved in the synthesis of glycogen. Glucagon

(and epinephrine) stimulate the phosphorylation and

inactivation of glycogen synthase.

HMG-CoA reductase (choice D) is the key enzyme

involved in the synthesis of cholesterol. Since this

is an anabolic process that occurs in the well-fed state,you would expect it to be stimulated by

insulin and inhibited by glucagon (which it is).

Pyruvate kinase (choice E) catalyzes the last reaction of

glycolysis. You would expect it to be

inhibited by glucagon (thus decreasing the amount ofglucose consumption). Glucagon promotes the

phosphorylation of pyruvate kinase, which renders it

inactive.

Which of the following inhibits the activity of acetyl-CoA

carboxylase?

A. Citrate

B. Glucagon

C. High-carbohydrate, low-fat diet

D. Insulin

Explanation:

The correct answer is B. The key thing to remember here

is that acetyl-CoA carboxylase catalyzes thefirst and rate-limiting step of fatty acid synthesis. If you

got that far, you could have figured

out which of the choices would inhibit the synthesis offatty acids. Certainly glucagon, a catabolic

hormone released in response to low blood glucose,

would be a likely candidate to inhibit the

synthesis of fatty acids. In fact, glucagon inhibits fattyacid synthesis by a cAMP-dependent

phosphorylation of acetyl-CoA carboxylase. Conversely,

glucagon stimulates fatty acid oxidation.

Citrate (choice A) is a key player in fatty acid synthesis(citrate shuttle). Therefore, the

presence of citrate would stimulate, not inhibit,acetyl-CoA carboxylase.

A high-carbohydrate, low-fat diet (choice C) wouldstimulate, not inhibit, the synthesis of fatty

acids.

In contrast to glucagon, insulin (choice D) is an anabolic

hormone that promotes fatty acid

synthesis and therefore would stimulate acetyl-CoAcarboxylase. It does so by dephosphorylating the

enzyme.


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An individual lacking the enzyme tyrosinase would be

particularly predisposed to develop which of thefollowing?

A. Glioblastoma multiforme

B. Hemangioblastoma

C. Hepatoma

D. Melanoma

E. Renal cell carcinoma

Explanation:

The correct answer is D. This question is simple if you

know that tyrosinase is an enzyme in the

biosynthetic pathway for melanin formation from

tyrosine. A lack of tyrosinase causes one form ofalbinism; a second form is caused by defective tyrosine

uptake. Patients with albinism are

vulnerable to developing cancers of the skin of all types,including basal cell carcinoma, squamous

cell carcinoma, and melanoma. The melanomas are

unusual in that they are non-pigmented (amelanotic)rather than black, since the patients cannot form

melanin.

A newborn baby has multiple hemorrhages. Clotting

studies demonstrate an elevated prothrombin time. An

abnormality of which of the following biochemicalprocesses is likely present in this patient?

A. Conversion of homocysteine to methionine

B. Conversion of methylmalonyl CoA to succinyl CoA

C. Degradation of cystathionine

D. Formation of gamma-carboxyglutamate residues

E. Hydroxylation of proline

Explanation:

The correct answer is D. Deficiency of vitamin K

produces a clotting disorder characterized by anelevated prothrombin time and easy bleeding,

particularly in neonates (hemorrhagic disease of the

newborn). The biochemical basis for this hemorrhagic

tendency is that glutamate residues on FactorsII (Thrombin), VII, IX, and X must be converted to

gamma-carboxyglutamate residues (in a vitamin K-

requiring reaction) for optimal activity.

The conversion of homocysteine to methionine (choiceA) requires vitamin B12.

Conversion of methylmalonyl CoA to succinyl CoA

(choice B) requires vitamin B12.

Degradation of cystathionine (choice C) requires vitamin

B6.

Hydroxylation of proline (choice E) requires vitamin C.

Vitamin C deficiency can cause easy bruising,

but will not prolong the prothrombin time.

A very ill infant is admitted to the hospital. Laboratory


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examination reveals a very high serum

concentration of lactic acid. In addition to taking steps

to correct the acidosis, the attendingphysician prescribes thiamine. The rationale for thiamine

administration is that thiamine is

converted to a coenzyme used by which of the following

enzymes?

A. Lactate dehydrogenase

B. Pyruvate carboxylase

C. Pyruvate dehydrogenase

D. Pyruvate kinase

E. Transketolase

Explanation:

The correct answer is C. Thiamine is a water-solublevitamin that is converted to the coenzyme

thiamine pyrophosphate. This coenzyme is used by

pyruvate dehydrogenase to convert pyruvate toacetyl coenzyme A. In the absence of thiamine, pyruvate

accumulates and can be converted by lactate

dehydrogenase to lactate, which is spilled in the bloodcausing lactic acidosis.

Lactate dehydrogenase (choice A) produces lactate frompyruvate but does not use thiamine

pyrophosphate.

Some lactic acidosis might be produced by decreased

pyruvate carboxylase activity (choice B), but

the enzyme requires biotin rather than thiaminepyrophosphate.

Pyruvate kinase (choice D) makes pyruvate fromphosphoenolpyruvate, but does not use thiamine

pyrophosphate.

Transketolase (choice E) requires thiamine

pyrophosphate, but operates in another pathway

(pentose

phosphate pathway). Decreased transketolase activity isnot associated with the development of

lactic acidosis.

A 69-year-old edentulous alcoholic male who lives alone

is admitted to the hospital for evaluation of a

shoulder wound that is not healing well. On physical

examination, numerous ecchymoses are noted onthe posterior aspect of his legs and thighs. Careful

examination of the man's skin reveals minute

hemorrhages around hair follicles and splinter

hemorrhages in the nail beds. Laboratory examination

is remarkable for a hemoglobin of 10 (normal 14-18g/dL); no other hematologic abnormalities are

noted. Therapy should consist of

A. administration of factor VIII

B. administration of iron

C. administration of vitamin B12

D. administration of vitamin C

E. administration of vitamin K


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Explanation:

The correct answer is D. The patient described suffersfrom scurvy, due to a deficiency of dietary

vitamin C. Absence of vitamin C leads to impaired

hydroxylation of proline residues in the nascent

procollagen chains, leading to weakness of blood vesselwalls. Clinically, the deficiency syndrome

is characterized by perifollicular hemorrhages,

fragmentation of hairs, purpura, ecchymoses,splinter hemorrhages, and hemorrhages into muscle. In

patients with normal dentition, gum changes(swelling, bleeding, loosening of teeth) are also noted.

Without supplementation with vitamin C,death may eventually occur.

Administration of factor VIII (choice A) would beindicated for factor VIII deficiency, which would

also lead to a prolonged PTT (partial thromboplastin

time), which was not noted.

Administration of iron (choice B) would be of benefit in

iron-deficiency anemia, but there is no

indication of a hypochromic, microcytic anemia in thispatient. The anemia of scurvy is typically

normochromic and normocytic, due to bleeding.

Administration of vitamin B12(choice C) would be

indicated for a megaloblastic anemia. Although a

macrocytic anemia may be observed in scurvy (due toconcomitant dietary folate deficiency or

perturbations in the folate pool), this patient did not

show macrocytosis.

Administration of vitamin K (choice E) would be

appropriate in the setting of vitamin K deficiency,which would produce prolongations of the prothrombin

time (PT), followed eventually by prolongation

of the PTT as the vitamin K-dependent factors (II, VII ,IX, X, protein C, and protein S) are

depleted.

A Guatemalan child with a history of meconium ileus is

brought in to a clinic because of a chronic

cough. The mother notes a history of respiratory tract

infections and bulky, foul-smelling stools.After assessment of the respiratory tract illness, the

practitioner should also look for signs of

A. cystinuria

B. hypoglycemia

C. iron deficiency anemia

D. sphingomyelin accumulation

E. vitamin A deficiency

Explanation:

The correct answer is E. The child is likely suffering from

cystic fibrosis. In this disorder, anabnormality of chloride channels causes all exocrine

secretions to be more viscous than normal.

Pancreatic secretion of digestive enzymes is oftenseverely impaired, with consequent steatorrhea

and deficiency of fat-soluble vitamins, including vitamin

A.

Cystinuria (choice A) is a relatively common disorder in


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which a defective transporter for dibasic

amino acids (cystine, ornithine, lysine, arginine; COLA)

leads to saturation of the urine withcystine, which is not very soluble in urine, and

precipitates out to form stones.

Hypoglycemia (choice B) is not a prominent feature ofchildren with cystic fibrosis who are on a

normal diet. Hyperglycemia may occur late in the course

of the disease.

Iron deficiency anemia (choice C) is not found with anyregularity in children with cystic fibrosis.

Sphingomyelin accumulation (choice D) is generally

associated with deficiency of sphingomyelinase,

as seen in Niemann-Pick disease.

In which of the following laboratory tests would you

expect to find the greatest disparity in reference

intervals between men and (non-pregnant) women?

A. Mean corpuscular volume

B. Serum alkaline phosphatase

C. Serum ferritin

D. Serum glucose

E. Serum sodium

Explanation:

The correct answer is C. Men have higher reference

intervals than women in tests related to iron andhemoglobin (Hb) concentration in blood. The normal

reference interval for Hb concentration in women

is lower (12.0-16.0 gm/dL) than that for men(13.5-17.5 gm/dL) due to lower serum testosterone

levels (testosterone is higher in men and stimulates

erythropoiesis) and blood loss during menses.Furthermore, women normally have about 400 mg of

iron (as ferritin) in their bone marrow iron stores

versus an average of 1000 mg of iron for men. In the

absence of inflammation, the small circulatingfraction of ferritin (choice C) correlates well with ferritin

stores in the bone marrow. Hence, men

have different reference intervals for serum ferritin thando women (15-200 ng/mL in men versus

12-150 ng/mL in women).

The mean corpuscular volume (choice A), serum alkalinephosphatase (choice B), serum glucose (choice

D), and serum sodium (choice E) are similar in both

sexes.

A competitive inhibitor of an enzyme will

A. alter the Vmax of the reaction

B. bind to the same site as the substrate

C. decrease the apparent Km for the substrate

D. decrease the turnover number

E. form an irreversible complex with the enzyme

Explanation:


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The correct answer is B. Substances that reduce the

activity of an enzyme are called inhibitors.

Reversible inhibitors bind to an enzyme but rapidlydissociate from it [in contrast to irreversible

inhibitors (choice E), which bind tightly and dissociate

very slowly from the enzyme]. There are

several types of reversible inhibitors:

Competitive inhibitors usually resemble the substrate

and compete with it for binding at the activesite (choice B). Thus, increasing the concentration of

substrate will decrease the percentinhibition of the enzyme. The Vmax is unchanged, but

the Km is increased.

A noncompetitive inhibitor binds with equal affinity to

both enzyme and enzyme-substrate complex.This binding leads to a distortion of the substrate

binding site, so new substrate cannot bind

and/or the product cannot be released. In this kind of

inhibition, the Vmax is decreased (choice A),but the Km is not altered. Adding more substrate will

not reverse this type of inhibition. This is

the equivalent of decreasing the turnover number(choice D).

An uncompetitive inhibitor does not bind to freeenzyme, but binds to the enzyme-substrate complex

at a site other than the catalytic site. Once bound by the

inhibitor, the enzyme is trapped in theenzyme-substrate complex state until the inhibitor

dissociates. In this kind of inhibition, the

slope of the reaction (which is the ratio Km/Vmax)remains the same, but both Vmax (choice A) and Km

(choice C) are reduced.

A 9-year-old child in a developing country is brought to

a clinic by his parents because he has trouble

keeping up with his classmates on the playground.Physical examination is remarkable for pulmonary

rales. Chest x-ray shows biventricular dilation of the

heart. Deficiency of which of the followingvitamins is the most likely cause of this child's condition

?

A. Ascorbic acid

B. Retinol

C. Riboflavin

D. Thiamine

E. Vitamin K

Explanation:

The correct answer is D. Thiamine deficiency is mostfrequently encountered in alcoholics and in

developing countries. Deficiency of this vitamin can takeseveral forms: dilated cardiomyopathy

(wet beriberi ), polyneuropathy (dry beriberi), and

mamillary bodydegeneration (Wernicke-Korsakoff syndrome).

Ascorbic acid (choice A, Vitamin C) deficiency causesscurvy, associated with capillary fragility,

bony abnormalities, and poor wound healing.

Retinol (choice B, Vitamin A) deficiency causes

blindness and impaired immune responses.


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Riboflavin ( choice C) deficiency causes cheilosis,

glossitis, and dermatitis.

Vitamin K (choice E) deficiency causes impaired blood

clotting because of decreased production offactors II, VII, IX , and X.

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

the pediatrician is examining the child, aconvulsion occurs. Stat serum chemistries demonstrate

severe hypoglycemia, hyperlipidemia, lacticacidosis, and ketosis. Physical examination is remarkable

for hepatomegaly, a finding confirmed by CTscan, which also reveals renomegaly. Which of the

following diseases best accounts for this

presentation?

A. Gaucher's disease

B. McArdle's disease

C. Niemann-Pick disease

D. Pompe's disease

E. Von Gierke's disease

Explanation:

The correct answer is E. Von Gierke's disease is a

glycogen storage disease caused by a deficiency

of glucose-6-phosphatase. It typically presents withneonatal hypoglycemia, hyperlipidemia, lactic

acidosis, and ketosis. Failure to thrive is common in

early life; convulsions may occur due toprofound hypoglycemia. The glycogen accumulation in

von Gierke's disease occurs primarily in the

liver and kidneys, accounting for the enlargement ofthese organs. Gout may develop later because of

the derangement of glucose metabolism.

Even if you don't remember all of the details of the

presentation of these genetic diseases, you

should be able to narrow the choices:

Gaucher's disease (choice A) and Niemann-Pick disease

(choice C) are lipid storage diseases, and

would not be expected to produce hypoglycemia.

The other diseases are glycogen storage diseases, but

McArdle's (choice B) and Pompe's (choice D)

disease affect muscle rather than liver, and would not beexpected to produce profound hypoglycemia

since the liver is the major source for blood glucose.

An individual with megaloblastic anemia is found to

have a significant folate deficiency. Erythropoiesisis hampered in this man due to his inability to perform

which type of enzymatic reaction?

A. Acyl transfer

B. Carboxylation

C. Decarboxylation

D. Hydroxylation

E. Methylation


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Explanation:

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

its most reduced form. TH4 can accept methyl,

methylene, or formyl carbons and transfer them as

methyl groups. This function is vital in nucleotide andamino acid synthesis.

Pantothenic acid is a key vitamin in acyl transferreactions (choice A). It forms part of coenzyme

A, which transfers acyl groups in

nishi's qb - biochemistry

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