A chronic alcoholic develops severe memory loss with marked confabulation. Deficiency of which of the following vitamins would be most likely to contribute to the neurologic damage underlying these symptoms?
A. Folic acid B. Niacin C. iboflavin D. !hiamine ". #itamin B
%$
"&planation'
!he correct answer is D. (ernicke)*orsakoff (ernicke)*orsakoff syndrome refers to the constellation of neurologic symptoms caused by thiamine deficiency. Among these+ a severe memory deficit+ which the patient may attempt to cover by making up bi,arre e&planations -confabulation+ -confabulation+ is prominent. Anatomical damage to the mamillary bodies and periventricular periventricular structures has been postulated as the cause. /n the 0.1.+ severe thiamine deficiency is seen most commonly in chronic alcoholics. !hiamine deficiency can also damage peripheral nerves -2dry2 beriberi and the heart -2wet2 beriberi. Folic acid deficiency -choice A produces megaloblastic anemia without neurologic symptoms. Niacin deficiency -choice B produces pellagra+ characteri,ed characteri,ed by depigmenting dermatitis+ chronic diarrhea+ and anemia. iboflavin deficiency -choice C produces ariboflavinosis+ ariboflavinosis+ characteri,ed by glossitis+ corneal opacities+ dermatitis+ and erythroid hyperplasia. #itamin B$% deficiency -choice " produces megaloblastic anemia accompanied by degeneration of the posterolateral spinal cord.
A %3)year)old woman with sickle cell anemia complains of steady pain in her right upper 4uadrant with radiation to the right shoulder+ especially after large or fatty meals. 5er physician diagnoses gallstones. 6f which of the following compounds are these stones most likely composed?
A. Calcium bilirubinate B. Calcium o&alate
C. Cholesterol D. Cholesterol and calcium bilirubinate ". Cystine
"&planation'
!he correct answer is A. Bilirubin is a degradative product of hemoglobin metabolism. Bilirubin -pigment stones are specifically specifically associated with e&cessive bilirubin production in hemolytic anemias+ including sickle cell anemia. Bilirubin stones can also be seen in hepatic cirrhosis and liver fluke infestation. Calcium o&alate stones -choice B and cystine stones -choice " are found in the kidney+ rather than the
gallbladder.
7ure cholesterol stones -choice C are less common than mi&ed gallstones+ but have the same risk factors+ including obesity and multiple pregnancies. 8i&ed stones -choice D are the common 2garden variety2 gallstones+ found especially in obese+ middle aged patients+ with a female predominance.
!wo sisters are diagnosed with hemolytic anemia. !heir older brother was previously diagnosed with the same disorder. !wo other brothers are asymptomatic. asymptomatic. !he mother and father are second cousins. Deficiency of which of the following en,ymes would be most likely to cause this disorder?
A. Debranching en,yme B. 9lucose):)phosphatase 9lucose):)phosphatase C. 9lucose):)phosphate 9lucose):)phosphate dehydrogenase D. 8uscle phosphorylase ". 7yruvate kinase
"&planation'
!he correct answer is ". /n general+ you should associate hemolytic anemia with defects in glycolysis or the he&ose monophosphate shunt -pentose phosphate pathway. 6nly two en,ymes of those listed in the answer choices specifically specifically involve these pathways and cause hemolytic anemia' pyruvate kinase and glucose):)phosphate dehydrogenase. 9lucose):)phosphate 9lucose):)phosphate dehydrogenase -9:7D deficiency is inherited as
C. Cholesterol D. Cholesterol and calcium bilirubinate ". Cystine
"&planation'
!he correct answer is A. Bilirubin is a degradative product of hemoglobin metabolism. Bilirubin -pigment stones are specifically specifically associated with e&cessive bilirubin production in hemolytic anemias+ including sickle cell anemia. Bilirubin stones can also be seen in hepatic cirrhosis and liver fluke infestation. Calcium o&alate stones -choice B and cystine stones -choice " are found in the kidney+ rather than the
gallbladder.
7ure cholesterol stones -choice C are less common than mi&ed gallstones+ but have the same risk factors+ including obesity and multiple pregnancies. 8i&ed stones -choice D are the common 2garden variety2 gallstones+ found especially in obese+ middle aged patients+ with a female predominance.
!wo sisters are diagnosed with hemolytic anemia. !heir older brother was previously diagnosed with the same disorder. !wo other brothers are asymptomatic. asymptomatic. !he mother and father are second cousins. Deficiency of which of the following en,ymes would be most likely to cause this disorder?
A. Debranching en,yme B. 9lucose):)phosphatase 9lucose):)phosphatase C. 9lucose):)phosphate 9lucose):)phosphate dehydrogenase D. 8uscle phosphorylase ". 7yruvate kinase
"&planation'
!he correct answer is ". /n general+ you should associate hemolytic anemia with defects in glycolysis or the he&ose monophosphate shunt -pentose phosphate pathway. 6nly two en,ymes of those listed in the answer choices specifically specifically involve these pathways and cause hemolytic anemia' pyruvate kinase and glucose):)phosphate dehydrogenase. 9lucose):)phosphate 9lucose):)phosphate dehydrogenase -9:7D deficiency is inherited as
an ;)linked recessive trait+ so females would not be affected. 7yruvate kinase is a glycolytic en,yme< pyruvate kinase deficiency is an autosomal recessive disorder+ affecting males and females appro&imately e4ually. /f this en,yme is deficient+ red cells have trouble producing enough A!7 to maintain the Na=>*= pump on the plasma membrane+ secondarily causing swelling and lysis. Debranching en,yme -choice A defects produce Coris disease+ one of the glycogen storage diseases. Defects in glucose):)phosphatase glucose):)phosphatase -choice B produce #on 9ierkes disease+ one of the glycogen storage diseases. 9lucose):)phosphatase 9lucose):)phosphatase dehydrogenase -choice C deficiency produces an ;)linked hemolytic anemia. Defects in muscle phosphorylase -choice D produce 8cArdles disease+ one of the glycogen storage diseases.
(hich of the following amino acids would most likely be found on the surface of a protein molecule?
A. Alanine B. Arginine C. /soleucine D. @eucine ". 7henylalanine F. !ryptophan
"&planation'
!he correct answer is B. !his 4uestion re4uires 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. Ne&t+ you need to figure out which of the amino acids listed is hydrophilic. /f you recall that arginine is a basic amino acid that is positively charged at physiologic p5+ you should be able to answer this 4uestion right away. All of the other choices have neutral side chains and are uncharged at physiologic p5. !hey 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 " and tryptophan -choice F have aromatic side chains.
A 1outheast Asian immigrant child is noted to be severely retarded. 7hysical e&amination e&amination reveals a pot) bellied+ pale child with a puffy face. !he childs tongue is enlarged. Dietary deficiency of which of the following substances can produce this pattern?
A. Calcium B. /odine C. /ron D. 8agnesium ". 1elenium
"&planation'
!he correct answer is B. !he disease is cretinism+ characteri,ed by a profound lack of thyroid hormone in a developing child+ leading to mental retardation and the physical findings described in the 4uestion stem. Cretinism can be due to dietary deficiency of iodine -now rare in this country because of iodi,ed salt+ to developmental failure of thyroid formation+ or to a defect in thyro&ine synthesis. Calcium deficiency -choice A in children can cause osteoporosis or osteopenia. /ron deficiency -choice C can cause a hypochromic+ microcytic anemia. 8agnesium deficiency -choice D is uncommon+ but can cause decreased refle&es+ and blunts the parathyroid response to hypocalcemia. 1elenium deficiency -choice " is rare+ but may cause a reversible form of cardiomyopathy.
!o which of the following diseases is pyruvate kinase deficiency most similar clinically? clinically?
A. alpha<)thalassemia alpha<)thalassemia B. beta<)thalassemia beta<)thalassemia C. 9lucose):)phosphate 9lucose):)phosphate dehydrogenase deficiency D. 5ereditary spherocytosis ". /ron deficiency anemia
"&planation'
!he correct answer is C. Both pyruvate kinase deficiency and glucose):)phosphate dehydrogenase deficiency are red cell en,yme deficiencies characteri,ed clinically by long 2normal2 periods interspersed with episodes of hemolytic anemia triggered by infections and o&idant drug inury -antimalarial drugs+ sulfonamides+ nitrofurans. /n both of these conditions+ the cell morphology between hemolytic episodes is usually normal or close to normal. !he alpha<-choice A and beta<-choice B thalassemias+ in their maor forms+ are characteri,ed by persistent severe anemia. /n the trait forms+ they are characterti,ed by mild anemia. 5ereditary spherocytosis -choice D is characteri,ed by intermittent hemolysis+ but+ unlike pyruvate kinase deficiency and glucose):)phosphate dehydrogenase deficiency+ o&idant drugs are not a specific trigger for hemolysis. /ron deficiency anemia -choice " is characteri,ed by chronic anemia with hypochromic+ microcytic erythrocytes.
A baby that was apparently normal at birth begins to show a delay in motor development by months of age. At one 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 %3. !his patients condition is due to an en,yme deficiency in which of the following biochemical pathways?
A. 9anglioside metabolism B. 8onosaccharide metabolism C. 7urine metabolism D. 7yrimidine metabolism ". !yrosine metabolism
"&planation'
!he correct answer is C. !he patient has a classical case of @esch)Nyhan syndrome+ an ;)linked disorder due to severe deficiency of the purine salvage en,yme hypo&anthine)guanine phosphoribosyl transferase -57!.
!his defect is associated with e&cessive de novo purine synthesis+ hyperuricemia+ and the clinical signs and symptoms described in the 4uestion stem. !he biochemical basis of the often striking self)mutilatory behavior -which may re4uire restraints and even tooth e&traction has never been established. !reatment with allopurinol inhibits &anthine o&idase and reduces gouty arthritis+ urate stone formation+ and urate nephropathy. /t does not+ however+ modify the neurologic>psychiatric presentation.
An obese individual is brought to the emergency room by a concerned friend. !he patient has been on a self)imposed 2starvation diet2 for four months+ and has lost : pounds while consuming only water and vitamin pills. /f e&tensive blood studies were performed+ which of the following would be e&pected to be elevated?
A. Acetoacetic acid B. Alanine C. Bicarbonate D. Chylomicrons ". 9lucose
"&planation'
!he correct answer is A. @ong)term starvation induces many biochemical changes. 8uch of the bodys energy re4uirements are normally supplied by serum glucose+ but in starvation are supplied by both glucose and lipid)derived ketone bodies+ including acetoacetic acid and beta)hydro&ybutyric acid. 9lucose cannot be synthesi,ed from lipids+ and is instead made from amino acids such as alanine in the process of gluconeogenesis. 1erum 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. 9lucose -choice " is maintained in the blood at a much lower than normal level during starvation.
A $3)year)old girl is seen by a dermatologist for removal of multiple s4uamous cell carcinomas of the skin. !he patient has nearly white hair+ pink irises+ very pale skin+ and a history of burning easily when e&posed to the sun. !his patients condition is caused by a disorder involving which of the following substances?
A. Aromatic amino acids B. Branched chain amino acids C. 9lycolipids D. 9lycoproteins ". 1ulfur)containing amino acids
"&planation'
!he correct answer is A. !he disease is albinism. !he most common form of albinism is caused by a deficiency of copper)dependent tyrosinase -tyrosine hydro&ylase+ 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 s4uamous cell carcinomas and melanomas. 8aple syrup urine disease is an e&le of a disorder of branched chain amino acids -choice B causing motor abnormalities and sei,ures. !ay)1achs disease is an e&le of a disorder of glycolipids -choice C. /n this disorder+ a deficiency of he&osaminidase A leads to accumulation of ganglioside 98%. 5unters disease is an e&le of a disorder of glycoproteins -choice D. !his mucopolysaccharidosis is inherited as an autosomal recessive trait. 5omocystinuria disease is an e&le of a disorder of sulfur)containing amino acids -choice ".
A E)year)old boy is referred to a specialty clinic because of digestive problems. 5e often e&periences severe abdominal cramps after eating a high fat meal. 5e is worked up and diagnosed with a genetic defect resulting in a deficiency of lipoprotein lipase. (hich of the following substances would most likely be elevated in this patients plasma following a fatty meal?
A. Albumin)bound free fatty acids B. Chylomicrons
C. 5D@ D. @D@ ". 0nesterified fatty acids
"&planation'
!he correct answer is B. After eating a high fat meal+ triglycerides are processed by the intestinal mucosal cells. !hey are assembled in chylomicrons and eventually sent into the circulation for delivery to adipocytes and other cells. Chylomicrons are too large to enter cells+ but are degraded while in the circulation by lipoprotein lipase. A defect in this en,yme 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. 5D@ -choice C is not a carrier of dietary fat from the intestine. @D@ -choice D would be not be elevated in this patient after a high fat meal. 5owever+ #@D@ would be elevated if the patient ate a high carbohydrate meal. /n this situation+ the carbohydrate would be converted into fat in the liver and sent out into circulation as #@D@. #@D@ would be unable to be degraded to @D@ and+ therefore+ would accumulate. A defect in lipoprotein lipase would cause a decrease+ not an elevation of unesterified fatty acids -choice "+ since the chylomicrons contain esterified fatty acids.
A )year)old man in a rural area presents to a physician for an employment physical. 6cular e&amination reveals small opa4ue rings on the lower edge of the iris in the anterior chamber of the eye. Nodular lesions are found on his Achilles tendon. 1uccessful therapy should be aimed at increasing which of the following gene products in hepatocyte cell membranes?
A. Apo B)$ B. Apo B)$ receptor C. Apo " D. Apo " receptor ". @ecithin cholesterol acyltransferase
"&planation'
!he correct answer is B. !his man has characteristic signs of familial hypercholesterolemia+ an autosomal dominant disorder affecting about $ in 3 persons. !he &anthomas on the Achilles tendon and the arcus lipoides -the opa4ue rings in the eye are pathognomonic. Affected individuals have very high @D@ cholesterol because of deficient endocytosis of @D@ particles by @D@ receptors. !hese receptors recogni,e the apo B)$ protein cotransported with cholesterol esters in @D@. !reatments aim at increasing genetic e&pression of @D@ receptors -i.e.+ apo B)$ receptors to enhance clearance of @D@ particles. Dietary changes+ a resin drug+ niacin+ or an 589)CoA reductase inhibitor could be tried. Apo B)$ -choice A is the apoprotein of liver)produced lipoproteins such as #@D@+ /D@ and @D@. /t is therefore not in the hepatic cell membranes+ and it might be e&pected to decrease with decreasing concentrations of circulating @D@. Apo " -choice C is an apoprotein found on #@D@+ /D@+ and chylomicrons+ allowing 2scavenging2 by the liver of remnants or of the lipoprotein itself. /t is not found in the hepatocyte membrane. Apo " receptor -choice D would actually be increased by the treatment with hypocholesterolemic agents. 5owever+ the apo " receptor is not involved in the scavenging of @D@ particles. @ecithin cholesterol acyl transferase -choice " or @CA!+ is activated by apo A/+ and esterifies free cholesterol in plasma. 7lasma levels of 5D@ cholesterol and apo A/ are inversely related to the risk of coronary heart disease.
(hich of the following structures is common to all sphingolipids?
A. Carnitine B. Ceramide C. Diacylglycerol D. 1phingomyelin ". 14ualene
"&planation'
!he correct answer is B. 1phingolipids 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. 1phingolipids can be differentiated on the basis of the 2;2 group that is esterified to the terminal hydro&yl group of ceramide. Carnitine -choice A is involved in the o&idation 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. !he second alcohol -e.g.+ choline+ ethanolamine+ serine contributes the polar head that distinguishes the different classes of phospholipids. @ike sphingolipids+ phospholipids are found in membranes. 1phingomyelin -choice D is a sphingolipid with phosphocholine as its 2;2 group. /t is a component of the myelin sheath. 14ualene -choice " is a )carbon intermediate in the synthesis of cholesterol.
A GE)year)old male patient presents with painful arthritis in the right big toe and uric acid renal stones. 5e has been taking allopurinol for his condition. (hat 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 synthesi,e non)essential amino acids D. Defective topoisomerases ". /ncreased levels of leukotrienes
"&planation'
!he correct answer is B. !his patient has gout+ characteri,ed by painful oints due to the precipitation of uric acid crystals caused by e&cessive production of uric acid -a minority of cases are associated with undere&cretion of uric acid. *idney disease is also seen due to accumulation of uric acid in the tubules. !he disease mostly affects males+ and is fre4uently treated with allopurinol+ an inhibitor of &anthine o&idase. ;anthine o&idase cataly,es the se4uential o&idation of hypo&anthine to &anthine to uric acid. A defect in urea synthesis -choice A would result in the accumulation of ammonia.
7henylketonuria is a disease in which tyrosine cannot be produced from phenylalanine -choice C. /t is characteri,ed by a musty body odor and mental retardation. Defective topoisomerases -choice D would affect DNA unwinding+ and therefore replication.
@eukotrienes -choice " 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 testing reveals a severe deficiency of galactose)$)phosphate uridyltransferase+ consistent with homo,ygosity. /f this condition goes untreated+ what is the likely outcome for this patient?
A. Benign disease e&cept for cataract formation B. Chronic emphysema appearing in early adulthood C. Chronic renal failure appearing in adolescence D. Death in infancy ". 9astrointestinal symptoms that remit with puberty
"&planation'
!he correct answer is D. 9alactosemia occurs in two very different clinical forms. Deficiency of galactokinase produces very mild disease with the only significant complication being cataract formation. /n contrast+ homo,ygous deficiency of galactose)$)phosphate uridyltransferase produces severe disease culminating in death in infancy. /n addition to galactosemia and galactosuria+ these patients have impaired renal tubular resorption leading to aminoaciduria+ gastrointestinal symptoms+ hepatosplenomegaly+ cataracts+ bleeding diathesis+ hypoglycemia+ and mental retardation. 7athologically+ the CN1 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 homo,ygous galactose)$)phosphate uridyltransferase deficiency+ but rather with alpha $)antitrypsin deficiency. /mpaired tubular reabsorption -producing aminoaciduria is seen within a few days or weeks of feeding milk to an infant with severe galactosemia+ as opposed to chronic renal failure appearing in adolescence -choice C.
9astrointestinal symptoms -choice " certainly occur in homo,ygous galactose)$)phosphate uridyltransferase deficiency+ but they would not be e&pected to remit with puberty. /nstead+ most untreated infants with this disorder show failure to thrive and die in infancy from wasting and inanition.
A %)year old female who is % months pregnant remembers that she had phenylketonuria -7*0 as a child and re4uired a special diet. !ests confirm markedly elevated maternal serum levels of phenylalanine and phenylacetic acid. 9enetic studies have not been performed on the father. (hat should the physician 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 re4uired to ascertain if the fetus is at risk. C. !he fetus is at no health risk if it is hetero,ygous for the 7*0 gene. D. !he fetus is at no health risk if phenylalanine levels are normali,ed by the third trimester. ". !he mothers hyperphenylalaninemia may have already harmed the fetus.
"&planation'
!he correct answer is ". 7henylalanine crosses the placenta and+ if maternal serum levels are elevated+ acts as a teratogen to the developing fetus. !his condition is known as maternal 7*0. 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 7*0 in a child+ the fetus is still at risk from maternal 7*0. Further information regarding the cause of this womans hyperphenylalaninemia -choice B is not needed+ since the fetus is e&posed to teratogenic levels of phenylalanine. Children born to mothers with untreated 7*0 develop maternal 7*0 even if they are hetero,ygous for the 7*0 gene -choice C. Fetal phenylalanine hydro&ylase cannot compensate for the high maternal levels of phenylalanine. !he critical period in development during which teratogenic materials affect the growing organs is between the rd and th weeks of gestation. By the end of the %nd month -compare with choice D+ the damage caused by the maternal 7*0 has already occurred.
A %G)year)old graduate student presents to a physician with complaints of severe muscle cramps and weakness with even mild e&ercise. 8uscle biopsy demonstrates glycogen accumulation+ but hepatic biopsy is unremarkable. (hich of the following is the most likely diagnosis?
A. 5artnups disease B. *rabbes disease C. 8cArdles disease D. Niemann)7ick disease ". #on 9ierkes disease
"&planation'
!he correct answer is C. A variety of glycogen storage diseases e&ist+ corresponding to defects in different en,ymes in glycogen metabolism< most of these involve the liver. 8cArdles disease -!ype # glycogen storage disease+ due to a defect in muscle phosphorylase+ is restricted to skeletal muscle. !he presentation described in the 4uestion stem is typical. 8any affected individuals also e&perience myoglobinuria. Definitive diagnosis is based on demonstration of myophosphorylase deficiency. 5artnups disease -choice A is a disorder of amino acid transport. *rabbes disease -choice B is a lysosomal storage disease. Niemann)7ick disease -choice D is a lysosomal storage disease. #on 9ierkes disease -choice " is a glycogen storage disease with prominent involvement of liver+ intestine+ and kidney.
(hich of the following metabolic processes occurs e&clusively in the mitochondria?
A. Cholesterol synthesis B. Fatty acid synthesis C. 9luconeogenesis D. 9lycolysis ". 5e&ose monophosphate shunt
F. *etone body synthesis 9. 0rea cycle
"&planation'
!he correct answer is F. 6f the processes listed+ only ketone body synthesis occurs e&clusively in the mitochondria. 6ther mitochondrial processes include the production of acetyl)CoA+ the !CA cycle+ the electron transport chain+ and fatty acid o&idation. 7rocesses that occur e&clusively in the cytoplasm include cholesterol synthesis -choice A< in cytosol or in "+ fatty acid synthesis -choice B+ glycolysis -choice D+ and the he&ose monophosphate shunt -choice ". Note that gluconeogenesis -choice C and the urea cycle -choice 9 occur in both the mitochondria and the cytoplasm.
A physician from the 0nited 1tates 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 a patient with glucose):)phosphate dehydrogenase deficiency. (hich of the following will be the most likely clinical presentation of this patient?
A. A :)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 ". An adult who develops severe shortness of breath during an airplane ride
"&planation'
!he correct answer is B. /n Africa+ the classic presentation of glucose):)phosphate dehydrogenase deficiency is a child who eats a meal of beans -#icia fava and several hours later develops hemoglobinuria and peripheral vascular collapse secondary to intravascular hemolysis as a result of the o&idant inury 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 unconugated bilirubin and a fall in haptoglobin. !he episode usually resolves
spontaneously several days later. !oday+ the classic presentation is less common in developed countries than is a slower onset syndrome beginning $) days after starting an antimalarial drug+ sulfonamide+ or other antio&idant drug. arely+ glucose):)phosphate dehydrogenase deficiency presents as neonatal aundice or with chronic hemolysis.
A patient with familial hypercholesterolemia undergoes a detailed serum lipid and lipoprotein analysis. 1tudies demonstrate elevated cholesterol in the form of increased @D@ without elevation of other lipids. !his patients hyperlipidemia is best classified as which of the following types?
A. !ype $ B. !ype %a C. !ype %b D. !ype ". !ype 3
"&planation'
!he correct answer is B. 5yperlipidemia has been subclassified based on the lipid and lipoprotein profiles. !ype %a+ which this patient has+ can be seen in a hereditary form+ known as familial hypercholesterolemia+ and also in secondary+ ac4uired forms related to nephritic syndrome and hyperthyroidism. !he root problem appears to be a deficiency of @D@ receptors+ which leads to a specific elevation of cholesterol in the form of increased @D@. 5etero,ygotes for the hereditary form generally develop cardiovascular disease from to 3 years of age. 5omo,ygotes may have cardiovascular disease in childhood. !ype $ -choice A is characteri,ed by isolated elevation of chylomicrons. !ype %b -choice C is characteri,ed by elevations of both cholesterol and triglycerides in the form of @D@ and #@D@. !ype -choice D is characteri,ed by elevations of triglycerides and cholesterol in the form of chylomicron remnants and /D@. !ype 3 -choice " is characteri,ed by elevations of triglycerides and cholesterol in the form of #@D@ and chylomicrons.
During the isolation of 8et)enkephalin -!yr)9ly)9ly)7he)8et from post)mortem human brain tissue+ researchers find that the peptide is rapidly degraded by peptidases in $ minute at E C. Detailed analysis of the peptide cleavage pattern of 8et)enkephalin is investigated with two candidate en,ymes. 0sing the drug bestatin+ the investigators found no detectable !yr)9ly)9ly)7he)8et but did find significant concentrations of !yr)9ly)9ly. 0sing thiorphan+ there was no detectable !yr)9ly)9ly)7he)8et+ but there was a high concentration of !yr. (hich of the following is the best conclusion about 8et)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 carbo&ypeptidase in the degradative pathway C. Bestatin inhibits an endopeptidase in the degradative pathway D. !hiorphan inhibits an aminopeptidase+ and bestatin inhibits an endopeptidase in the degradative pathway ". !hiorphan inhibits an aminopeptidase in the degradative pathway
"&planation' !he correct answer is A. 8et)enkephalin+ the most abundant opioid peptide in the human brain+ undergoes two routes of metabolism. 6ne route releases a tripeptide and therefore is the result of a peptidase that cuts an amino acid bond within the molecule' an endopeptidase. !he other route releases free tyrosine and therefore is an e&opeptidase. "&opeptidases can remove amino acid residues from the amino) or carbo&yl)terminus of the protein. By convention+ all peptide se4uences are given from the N to the C terminus+ the direction of translation. !yrosine is therefore at the amino)terminus of 8et)enkephalin+ and its release is the result of digestion by an aminopeptidase. !he scientists have used two drugs to highlight the two en,ymatic pathways. (ith bestatin+ 8et) enkephalin is metaboli,ed only to the tripeptide< therefore bestatin inhibits the aminopeptidase en,yme+ preventing release of free tyrosine residues. (ith thiorphan+ 8et)enkephalin is metaboli,ed to free tyrosine< the tripeptide is no longer formed. !hiorphan is an inhibitor of the endopeptidase. !he lack of persistence of 8et)enkephalin in the presence of an en,yme inhibitor is evidence that the peptides metabolism is shifted in the direction of the noninhibited en,yme. A schematic of the metabolism would be'
!yrosine cannot be the result of carbo&ypeptidase activity -choice B+ since the carbo&yl)terminus of 8et)enkephalin is a methionine. Bestatin inhibits an aminopeptidase+ not an endopeptidase -choice C. An endopeptidase would not release a free amino acid residue. 8et)enkephalin is indeed metaboli,ed by an aminopeptidase and an endopeptidase+ but bestatin inhibits the aminopeptidase and thiorphan inhibits the endopeptidase -compare with choice D. !hiorphan does not inhibit an aminopeptidase -choice "< furthermore+ such an en,yme would release a free !yr and a tetrapeptide.
!he parents of a :)month)old child who was normal at birth bring her into the clinic. 1ince their emigration to the 0.1. from "astern "urope soon after her birth+ the child has developed diminished responsiveness+ progressive blindness and deafness+ and recently+ sei,ures. 1erum levels of which of the following compounds would be e&pected to be decreased in both of the parents?
A. Dystrophin B. 5e&osaminidase A C. 5ypo&anthine)guanine phosphoribosyltransferase -597! D. 7henylalanine hydro&ylase ". #itamin D
"&planation'
!he correct answer is B. !his patient has !ay)1achs disease+ an autosomal recessive disorder caused by the deficiency of he&osaminidase A+ which leads to the accumulation of ganglioside 98% in neurons+ producing a degenerative neurologic disease. Children appear normal at birth+ but then begin to suffer from diminished responsiveness+ deafness+ blindness+ loss of neurologic function+ and sei,ures. A cherry)red spot on the macula may be seen by ophthalmoscopic e&amination. Death usually occurs by G to 3 years of age. !here is no therapy. !he incidence is higher among Hews of "astern "uropean descent. 1ince the parents must be hetero,ygotes for the mutant he&osaminidase A allele+ they would be e&pected to have diminished levels of the en,yme. A defect in the dystrophin -choice A gene produces Duchenne muscular dystrophy+ characteri,ed by onset of
weakness in early childhood. A severe deficiency in 597! -choice C will lead to @esch)Nyhan syndrome+ characteri,ed by e&cessive uric acid production+ mental retardation+ spasticity+ self)mutilation+ and aggressive+ destructive behavior. Deficiency of phenylalanine hydro&ylase -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. 5ypophosphatemic rickets is an ;)linked dominant condition causing abnormal regulation of vitamin D -choice " metabolism and defects in renal tubular phosphate transport. 1ymptoms include growth retardation+ osteomalacia+ and rickets.
7oor o&ygenation of tissues decreases the production of A!7 necessary for many cellular functions. (hich of the following processes is most immediately compromised in a typical cell when A!7 production is inade4uate?
A. Comple& carbohydrate synthesis B. @ipid synthesis C. Na=>*= A!7ase function D. Nucleic acid synthesis ". 7rotein synthesis
"&planation'
!he correct answer is C. (hile A!7 is important in cellular synthetic functions+ its role in maintaining the Na=> *= e&change across the plasmalemma is actually the most immediately important function for most cells. !he direct effect of this is the energy -A!7 driven e&change of Na= ions -which go from inside the cell to outside for % *= ions -which go from outside to inside. !his process re4uires considerable energy -$ A!7 per Na=>%*= e&change+ since both the Na= and *= are traveling against a concentration gradient. !his direct effect of the Na=> *= A!7ase may seem trivial+ but the secondary conse4uences are dramatic. !he Na=> *= A!7ase helps establish the transmembrane potential of the cell -because the 4uantitatively uneven e&change of Na=> *= drives more positive ions out of the cell than in and also both the Na= and *= gradients. All of these facilitate a wide variety of e&changes and transmembrane transport systems that allow entry into the cell of the
large variety of small molecules and ions that it needs. !he first microscopically visible effect of significant hypo&ia is cellular edema+ which is a conse4uence of distorted water balance+ also an indirect function of the Na=> *= A!7ase.
0rine screening of an apparently healthy pregnant woman demonstrates a positive Clinitest reaction. 5owever+ blood glucose levels were within normal limits+ and more specific testing for urine glucose is negative. !he woman has been unaware of any metabolic problems and has been living a normal life. Deficiency of which of the following en,ymes would most likely produce this presentation?
A. Fructokinase B. Fructose $)phosphate aldolase C. 9alactose $)7)uridyl transferase D. @actase ". 7yruvate dehydrogenase
"&planation' !he correct answer is A. 9lucose+ 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. !his leaves three possibilities' fructokinase+ fructose $)phosphate aldolase+ and galactose $)7)uridyl transferases. 6f these+ only fructokinase deficiency produces a mild -usually completely asymptomatic condition known as fructosuria. Fructose $)phosphate aldolase deficiency -choice B produces severe hereditary fructose intolerance. 9alactose $)7)uridyl transferase deficiency -choice C produces classic galactosemia. @actase deficiency -choice D produces lactose intolerance. 7yruvate dehydrogenase deficiency -choice " produces severe disease -e.g.+ a subset of @eighs disease.
Addition of which of the following e&haustively $GC labeled substrates would lead to evolution of $GC6% from a cell)free suspension containing all the en,ymes and substrates re4uired for the synthesis of uridylic acid?
A. Aspartate B. Carbamoyl phosphate C. 9lutamine D. 9lycine ". N$)Formyltetrahydrofolate
"&planation'
!he correct answer is A. /n the first step of pyrimidine synthesis+ carbamoyl phosphate condenses with aspartate to form carbamoyl aspartate+ in a reaction cataly,ed by aspartate transcarbamoylase. /n subse4uent steps+ ring closure occurs with the loss of water+ followed by o&idation to yield orotic acid. Addition of ribose)3) phosphate produces orotidylic acid+ which is decarbo&ylated by orotidylate decarbo&ylase to yield uridylic acid. !he carbon dio&ide that is evolved is derived from the alpha carbo&yl group of aspartate. Carbamoyl phosphate -choice B condenses with aspartate with the loss of inorganic phosphate to produce carbamoyl aspartate. !he carbamoyl moiety of carbamoyl phosphate is retained. 9lutamine -choice C+ glycine -choice D and N$)formyltetrahydrofolate -choice " are all used in purine synthesis. 9lutamine also donates an amino group to 0!7 to form C!7+ but this step occurs after the synthesis of uridylic acid is complete.
A histological section of the left ventricle of a deceased %)year)old white male shows classic contraction band necrosis of the myocardium. Biological specimens confirm the presence of cocaine and metabolites. Activity of which of the following en,ymes was most likely increased in the patients myocardial cells shortly prior to his death?
A. 7hosphoenolpyruvate carbo&ykinase B. 7hosphofructokinase)$ C. 7yruvate dehydrogenase D. 1uccinate dehydrogenase ". !ransketolase
"&planation'
!he correct answer is B. Cocaine causes contraction band necrosis by blocking the reuptake of norepinephrine+ resulting in e&cessive vasoconstriction of coronary vessels+ leading to ischemia and infarction of heart tissue. 0nder these pathological conditions+ myocardial cells switch to anaerobic metabolism and therefore glycolysis becomes the sole source of A!7 via substrate)level phosphorylations by phosphoglycerate kinase and pyruvate kinase. 7hosphofructokinase)$ -7F*)$ is the rate)limiting en,yme of glycolysis+ and its activity would therefore be increased. 7hosphoenolpyruvate carbo&ykinase -choice A is a regulatory en,yme in gluconeogenesis+ which is induced by cortisol+ epinephrine+ and glucagon. /t functions in the hepatic synthesis of glucose when energy levels from beta)o&idation of fatty acids are ade4uate. 7yruvate dehydrogenase -choice C produces acetyl)CoA from pyruvate and coen,yme A+ bridging glycolysis and the *rebs cycle. /t re4uires 3 cofactors+ including NAD and FAD+ which would no longer be produced by the electron transport under hypo&ic conditions+ decreasing its activity. 1uccinate dehydrogenase -choice D is a key en,yme of the *rebs cycle+ producing a reduced e4uivalent of FAD to feed into the electron transport chain. /t is also known as Comple& //. !he *rebs cycle only functions if o&ygen is in appropriate concentrations since it is regulated by the levels of NAD5+ which is only consumed by the electron transport chain if there is enough o&ygen. !he absence of o&ygen leads to an accumulation of NAD5 and a subse4uent decrease in the en,yme activities of the *rebs cycle. !ransketolase -choice " is a thiamine re4uiring en,yme of the non)o&idative half of the he&ose monophosphate shunt. !he shuffling of sugars in the second half of this pathway results in the reentry of glyceraldehyde))phosphate and fructose):)phosphate into the glycolytic pathway. !ransketolase activity in red blood cells is used as a clinical marker of thiamine deficiency+ markedly decreasing in disorders such as (ernicke)*orsakoff syndrome.
An )month)old child is brought to a pediatrician because of the mothers concern about the boys tendency to compulsively bite his fingers. 6n 4uestioning+ the mother reported that she has noticed yellow)orange crystals in his diapers+ but has not mentioned them to anyone. A genetic defect in which of the following pathways should be suspected?
A. Aromatic amino acid metabolism
B. Branched chain amino acid metabolism C. 7urine metabolism D. 7yrimidine metabolism ". 1ulfur)containing amino acid metabolism
"&planation'
!he correct answer is C. !he disease is @esch)Nyhan syndrome+ and the yellow)orange crystals of uric acid in the diaper are an important+ but often neglected+ clue to early diagnosis. @esch)Nyhan syndrome is characteri,ed by a tremendous overproduction of purines+ because the reutili,ation of purines via the purine salvage pathway is blocked by a near total absence of hypo&anthine)guanine phosphoribosyl) transferase -597! activity. 7atients with this severe ;)linked disease+ for reasons that are unknown+ show aggressive behavior that leads to self)mutilation. !hey may also develop gouty arthritis or gouty nephropathy. 7henylketonuria is an e&le of a disorder of aromatic amino acid metabolism -choice A characteri,ed by mental retardation. 8aple syrup urine disease is an e&le of a disorder of branched chain amino acids -choice B causing motor abnormalities and sei,ures. 6rotic aciduria is an e&le of a disorder of pyrimidine metabolism -choice D+ characteri,ed by retarded growth and development as well as megaloblastic anemia. 5omocystinuria is an e&le of a disorder of sulfur)containing amino acids -choice "+ characteri,ed by mental retardation+ dislocation of the lenses+ osteoporosis+ and thromboses.
(hich of the following will be unchanged in a @ineweaver)Burk plot of an en,yme with and without a competitive inhibitor?
A. *m B. 1lope C. &)intercept D. y)intercept
"&planation'
!he correct answer is D. /t is worth taking the time to learn how to read a @ineweaver)Burk plot. @ineweaver)Burk plots are used to determine the #ma& and *m of an en,yme< they are also used to differentiate between competitive and noncompetitive inhibition. Note that in a @ineweaver)Burk plot+ the slope is *m>#ma&+ the &)intercept is )$>*m+ and the y) intercept is $>#ma&. /n the presence of a competitive inhibitor+ the *m-choice A and therefore the slope -choice B are both increased. 1imilarly+ if *m is increased+ )$>*m will become less negative and the &)intercept will shift to the right. /ntuitively+ this makes sense since a competitive inhibitor will increase the amount of substrate needed to reach half)ma&imal velocity -definition of *m. /n contrast+ the #ma&+ and hence the y)intercept+ is unchanged -choice D.
(hich of the following metabolic alterations would most likely be present in a chronic alcoholic compared to a non)drinker?
A. Fatty acid o&idation is stimulated B. 9luconeogenesis is stimulated C. 9lycerophosphate dehydrogenase is stimulated D. !he ratio of lactate to pyruvate is decreased ". !he ratio of NAD5 to NAD= is increased
"&planation'
!he correct answer is ". !he principal route of metabolism of ethanol is via alcohol dehydrogenase+ which uses hydrogen from ethanol to form NAD5 from NAD=+ markedly increasing the ratio of NAD5 to NAD=. !he relative e&cess of NAD5 has a number of effects+ including inhibiting+ rather than stimulating fatty acid o&idation -choice A< inhibiting gluconeogenesis rather than stimulating it -choice B< inhibiting+ rather than stimulating -choice C glycerophosphate dehydrogenase< and favoring the formation of lactate rather than pyruvate from glycolysis -thereby increasing+ rather than decreasing the lactate>pyruvate ratio< choice D.
A couple brings in their :)month)old child because they are concerned about the childs inability to sit without support. !he physician interviews the parents and ascertains that they are both Ashkena,ic Hews. !he doctor should inform them that+ because of their heritage+ their child may have an increased risk of which of the following
disorders?
A. Albinism and galactosemia B. Cystic fibrosis and @esch)Nyhan disease C. 9auchers disease and !ay)1achs disease D. *rabbes disease and Niemann)7ick disease ". 8etachromatic leukodystrophy and phenylketonuria
"&planation'
!he correct answer is C. Iou should associate Ashkena,ic -"astern "uropean Hews with two diseases' !ay)1achs disease and !ype / 9auchers disease. Both of these diseases are sphingolipidoses. !ay) 1achs disease is the more devastating of the two+ and is characteri,ed by progressive neurologic -including visual deterioration beginning at about : months of age and leading to death by age . /n contrast+ !ype / 9auchers disease is compatible with a normal life span and causes hepatosplenomegaly with CN1 involvement. -!he infantile !ype // and the uvenile !ype /// forms cause more serious disease but are not seen with increased incidence in Ashkena,ic Hews. None of the other conditions listed occur with greater fre4uency in Ashkena,ic Hews. /n this case+ also note that many perfectly normal children cannot sit without support at : months of age+ so the child may well be healthy. A %)year)old retarded child is evaluated by a metabolic specialist. !he childs history is significant for failure to thrive and progressive neurologic deterioration+ including deafness and blindness. 7hysical e&amination is remarkable for hepatosplenomegaly+ as well as a cherry)red spot on funduscopic e&amination. !hese symptoms are consistent with a diagnosis of
A. 5unter syndrome B. Niemann)7ick disease C. 7ompes disease D. tyrosinosis ". von 9ierkes disease
"&planation'
!he correct answer is B. 5epatosplenomegaly accompanied by progressive neurologic deterioration should make you think of lipid storage diseases< Niemann)7ick disease is the only lipid storage disease in the answer choices. Niemann)7ick disease is due to a deficiency of sphingomyelinase+ leading to an accumulation of sphingomyelin. /t is most common among Ashkena,ic Hews and generally results in death by age %. !he cherry)red spot is also a characteristic of !ay)1achs disease+ but hepatosplenomegaly suggests Niemann)7ick disease rather than !ay)1achs. 5unter syndrome -choice A is a mucopolysaccharidosis+ inherited in an ;)linked recessive fashion. 7ompes disease -choice C is a glycogen storage disease characteri,ed by hypotonia and cardiorespiratory failure. !yrosinosis -choice D is a rare abnormality of tyrosine metabolism that would not produce the listed symptoms. von 9ierkes disease -choice " is a severe form of glycogen storage disease characteri,ed by hypoglycemia+ hepatomegaly+ and renomegaly.
26
(hich of the following en,ymes is located at arrow $ in the electron micrograph above?
A. Carnitine acyltransferase // B. Fatty acyl CoA synthetase C. 9lucose):)phosphate dehydrogenase D. 5e&okinase ". 7yruvate kinase
"&planation'
!he correct answer is A. Arrow $ indicates the inner mitochondrial membrane. Carnitine acyltransferase // is located on the inner face of the inner mitochondrial membrane. /t reforms fatty acyl CoA in the mitochondrial matri& -arrow 3 from acyl carnitine+ thus preparing it for mitochondrial o&idation. !he acyl groups on carnitine are derived from acyl CoA esters synthesi,ed 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 by arrow 2. Glucose-6-phosphate dehydroenase, the !irst en"yme in the pentose phosphate pathway (choice C), he#o$inase, the !irst en"yme in the lycolytic pathway (choice %), and pyru&ate $inase (choice '), which produces pyru&ate !rom phosphoenolpyru&ate in lycolysis, are all located in the cytosol, indicated by arrow . Arrow indicates smooth endoplasmic reticulum.
A E%)year)old woman+ in otherwise good health+ presents with megaloblastic anemia. Careful evaluation reveals 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 likely problem?
A. @ack of leafy green vegetables B. @ack of milk products C. @ack of red meat D. @ack of yellow vegetables ". 6vercooked food
"&planation' !he correct answer is ". Folates -pteroylglutamic acid and related compounds are widely distributed
in foodstuffs. Dietary deficiency is usually due to overcooked -folates are very labile and old -folates rapidly decay with time food.
A %)month)old boy is evaluated for failure to thrive. As the pediatrician is e&amining the patient+ she witnesses a sei,ure. 7hysical e&amination is remarkable for hepatomegaly+ a finding later confirmed by C! scan+ which also reveals renomegaly. 1erum chemistries demonstrate severe hypoglycemia+ hyperlipidemia+ lactic acidosis+ and ketosis. (hich of the following diseases best accounts for this presentation?
A. 9auchers disease B. 8cArdles disease C. Niemann)7ick disease D. 7ompes disease ". von 9ierkes disease
"&planation'
!he correct answer is ". von 9ierkes disease is a glycogen storage disease caused by a deficiency of glucose):)phosphatase. /t typically presents with neonatal hypoglycemia+ hyperlipidemia+ lactic acidosis+ and ketosis. Failure to thrive is common in early life< convulsions may occur due to profound hypoglycemia. !he glycogen accumulation in von 9ierkes disease occurs primarily in the liver and kidneys+ accounting for the enlargement of these organs. 9out may develop later because of the derangement of glucose metabolism. "ven if you do not remember all of the details of the presentation of these genetic diseases+ you should be able to narrow the choices' 9auchers disease -choice A and Niemann)7ick disease -choice C are lipid storage diseases+ and would not be e&pected to produce hypoglycemia. !he other diseases are glycogen storage diseases+ but 8cArdles -choice B and 7ompes -choice D disease affect muscle rather than liver and would not be e&pected to produce profound hypoglycemia+ since the liver is
the maor source for blood glucose.
A newborn appears normal at birth+ but develops vomiting and diarrhea accompanied by aundice and hepatomegaly within the first few weeks of life. (ithin months+ the baby has obvious cataracts and ascites. !he infant is switched to a milk)free diet+ which stabili,es but does not completely reverse his condition. By one year of age+ he has developed mental retardation. (hich of the following is the most likely diagnosis?
A. Cystic fibrosis B. 9alactosemia C. 8cArdles disease D. #on 9ierkes disease ". (ilsons disease
"&planation'
!he correct answer is B. 9alactosemia is an autosomal recessive disease caused by a deficiency of galactose)$)phosphate uridyltransferase+ which is necessary for the metabolism of the galactose derived from milk lactose. !he condition should be suspected in infants with growth failure+ cataracts+ liver disease+ aminoaciduria+ and mental retardation. A reducing sugar -galactose is usually present in the urine. 8ost of the pathology is related to the to&ic effects of galactose)$)phosphate. !reatment involves strict dietary lactose restriction+ which consists of more than simply withdrawal of milk products+ because lactose is also present in many non)diary foods. 1trict adherence to the diet can strikingly alter the course of this disease. Cystic fibrosis -choice A is associated with maldigestion+ pancreatic disease+ and pulmonary disease. 8cArdles disease -choice C is a glycogen storage disease that selectively affects muscle. #on 9ierkes disease -choice D is a glycogen storage disease affecting the liver and kidneys. (ilsons disease -choice " is a caused by a metabolic abnormality in the handling of copper that can cause cirrhosis and brain damage+ and usually presents in adolescence.
(hich of the following pairs of en,ymes is re4uired for the process of gluconeogenesis?
A. Fructose)$+:)bisphosphatase and pyruvate carbo&ylase B. 9lucose):)phosphatase and phosphofructokinase)$
C. 9lucose):)phosphatase and pyruvate dehydrogenase D. 7hosphoenolpyruvate carbo&ykinase and glucokinase ". 7yruvate kinase and pyruvate carbo&ylase
"&planation' !he correct answer is A.!he three irreversible steps of glycolysis are cataly,ed by he&okinase+ phosphofructokinase)$ -choice B+ and pyruvate kinase. /n gluconeogenesis+ other en,ymes are needed
to bypass these key steps. 7yruvate cannot be directly converted to phosphoenolpyruvate in gluconeogenesis. !herefore+ pyruvate carbo&ylase -a mitochondrial en,yme< choice A converts pyruvate to o&aloacetate+ which can be converted to phosphoenolpyruvate by phosphoenolpyruvate carbo&ykinase -choice D+ using two A!7 e4uivalents per molecule of phosphoenolpyruvate. Fructose)$+:)bisphosphatase -choice A is the en,yme that splits fructose)$+:)bisphosphate into fructose):)phosphate and inorganic phosphate. /t is also re4uired for gluconeogenesis. 9lucose):)phosphatase -choices B and C is a liver en,yme that hydroly,es glucose):)phosphate to glucose. A deficiency of this en,yme leads to von 9ierke disease+ also known as glycogen storage disease type /. 7yruvate dehydrogenase -choice C is a mitochondrial en,yme that converts pyruvate to acetyl CoA. !his en,yme re4uires thiamine pyrophosphate+ lipoamide+ and FAD as cofactors. 9lucokinase -choice D is a liver en,yme that converts glucose to glucose):)phosphate. 0nlike he&okinase+ it is specific for glucose and is unresponsive to the level of glucose):)phosphate. /ts function is to store e&cess glucose+ so it has a very high *m -ie+ a low affinity for glucose+ becoming active only when the concentration of glucose is very high. 7yruvate kinase -choice " cataly,es the conversion of phosphoenolpyruvate to pyruvate in the glycolytic pathway. /t is activated by fructose)$+:)bisphosphate+ the product of the committed step of glycolysis+ and is allosterically inhibited by A!7+ alanine+ and acetyl CoA.
A G)year)old+ formerly obese woman presents to her physician. 1he was very proud of having lost lbs. during the previous % years+ but now noticed that her 2hair is falling out.2 6n 4uestioning+ she reports having followed a strict fat)free diet. 5er alopecia is probably related to a deficiency of which of the following vitamins?
A. #itamin A B. #itamin C C. #itamin D D. #itamin " ". #itamin *
"&planation'
!he correct answer is A. (hile it is hard to develop a deficiency in oil)soluble vitamins -A+ D+ "+ * because the liver stores these substances+ deficiency states can be seen in chronic malnutrition -specifically chronic fat deprivation and chronic malabsorption. #itamin A is necessary for formation of retinal pigments -deficiency can cause night blindness and for appropriate differentiation of epithelial tissues -including hair follicles+ mucous membranes+ skin+ bone+ and adrenal corte&. #itamin C -choice B+ which is water soluble rather than oil soluble+ is necessary for collagen synthesis. #itamin D -choice C is important in calcium absorption and metabolism. #itamin " -choice D is a lipid antio&idant that is important in the stabili,ation of cell membranes. #itamin * -choice " is necessary for normal blood coagulation.
3 m@ of synovial fluid is aspirated from an inflamed knee oint. !he fluid is yellow)white and cloudy and contains %+ (BC>mm -3J neutrophils. Needle)shaped+ strongly negatively birefringent crystals are seen both within and outside neutrophils. !hese crystals most likely have which of the following compositions?
A. Basic calcium phosphate B. Calcium o&alate C. Calcium pyrophosphate dihydrate D. Cholesterol ". 8onosodium urate
"&planation'
!he correct answer is ". All the compounds listed can produce crystals in oint fluid+ but only monosodium urate -associated with gout and calcium pyrophosphate dihydrate -associated with C77D crystal deposition disease+ also called pseudogout+ and to lesser degree basic calcium phosphate -apatite)associated arthropathy+ have a high likelihood of being encountered on a step $ 018@" e&am. !he crystals described are those of monosodium urate. Be careful not to answer 2uric acid2 if that is listed as an alternative choice on an e&am+ since the 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 o&alate crystals -choice B are seen in primary o&alosis 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 and degenerative arthritis+ where they form large+ flat+ rhomboidal plates with notched corners.
(hich of the following cofactors is re4uired for decarbo&ylation of alpha)ketoacids?
A. #itamin B$ B. #itamin B% C. #itamin B D. #itamin B3 ". #itamin B:
"&planation'
!he correct answer is A. #itamin B$+ or thiamine+ is the coen,yme re4uired -as the pyrophosphate for the decarbo&ylation of alpha)ketoacids. An e&le of this reaction is pyruvate decarbo&ylase reaction in alcoholic fermentation. 6ther reactions such as that cataly,ed by pyruvate dehydrogenase also rely on thiamine pyrophosphate for decarbo&ylation+ but re4uire other cofactors as well. !hiamine is also re4uired for the generation of pentose phosphates for nucleotide synthesis in the pentose phosphate pathway -he&ose monophosphate shunt+ serving as a cofactor for transketolase. #itamin B%-choice B+ or riboflavin+ is a constituent of F8N -flavin mononucleotide and FAD -flavin adenine
dinucleotide. /t functions in hydrogen and electron transport. #itamin B-choice C+ or niacin -nicotinic acid+ is a coen,yme that is also involved in hydrogen and electron transport. Nicotinic acid functions in the form of NAD and NAD7. #itamin B3-choice D+ or pantothenic acid+ is conugated with coen,yme A to act as a carbo&ylic acid carrier. #itamin B:-choice "+ or pyrido&ine+ is re4uired as a cofactor for pyrido&al phosphate and pyrido&amine phosphate. Both of these cofactors are essential to protein metabolism and energy production.
A newborn presents with severe acidosis+ vomiting+ hypotonia+ and neurologic deficits. 1erum analysis reveals elevated levels of lactate and alanine. !hese observations suggest a deficiency in which of the following en,ymes?
A. Alanine aminotransferase B. 9lutamate dehydrogenase C. @actate dehydrogenase D. 7yruvate carbo&ylase ". 7yruvate dehydrogenase
"&planation'
!he correct answer is ". 7yruvate dehydrogenase -7D5 cataly,es the irreversible conversion of pyruvate to acetyl)CoA. /f 7D5 is absent+ pyruvate will be used in other pathways instead. 7yruvate will be converted to alanine via alanine aminotransferase -choice A and to lactate via lactate dehydrogenase -choice C. 9lutamate dehydrogenase -choice B is involved in o&idative deamination+ releasing ammonium ion for urea synthesis. Deficiency of this en,yme would not cause the symptoms described. 7yruvate carbo&ylase -choice D is a gluconeogenic en,yme that cataly,es the conversion of pyruvate to o&aloacetate. Deficiency of this en,yme would not cause the symptoms described.
!he activity of which of the following en,ymes is directly affected by citrate?
A. Fructose)%+:)bisphosphatase
B. /socitrate dehydrogenase C. 7hosphofructokinase / D. 7yruvate carbo&ylase ". :)phosphogluconate dehydrogenase
"&planation'
!he correct answer is C. Citrate is produced by citrate synthase from acetyl CoA and o&aloacetate. !his reaction takes place in the mitochondria+ but citrate can move freely from the mitochondria into the cytosol. (hen the citric acid cycle slows down+ citrate accumulates. /n the cytosol+ it acts as a negative allosteric regulator of phosphofructokinase /+ the en,yme that cataly,es the committed step of glycolysis. Fructose)%+:)bisphosphatase -choice A breaks down fructose)%+:)bisphosphate+ a potent allosteric activator of phosphofructokinase /. Fructose)%+:)bisphosphatase is activated by cyclic A87)dependent protein kinase. /socitrate dehydrogenase -choice B converts isocitrate to alpha)ketoglutarate in the citric acid cycle. /t is allosterically stimulated by AD7 and inhibited by A!7 and NAD5. !his reaction produces NAD5 and C6%. 7yruvate carbo&ylase -choice D is a mitochondrial en,yme that converts pyruvate to o&aloacetate. /t is important in gluconeogenesis and replenishes the o&aloacetate in the citric acid cycle. :)phosphogluconate dehydrogenase -choice " converts :)phosphogluconate to ribulose 3)phosphate in the pentose phosphate shunt pathway.
(hich of the following en,ymes is stimulated by glucagon?
A. Acetyl)CoA carbo&ylase B. 9lycogen phosphorylase C. 9lycogen synthase D. 589)CoA reductase ". 7yruvate kinase
"&planation'
!he correct answer is B. Before you started analy,ing all of the answer choices you should have reminded yourself that glucagon increases serum glucose. 1o an en,yme stimulated by glucagon might be involved in either the breakdown of glycogen to glucose -glycogenolysis or in the creation of glucose from noncarbohydrate precursors -gluconeogenesis. 9lycogen phosphorylase cataly,es the first step in glycogenolysis< it makes sense that it would be stimulated by glucagon. Acetyl)CoA carbo&ylase -choice A cataly,es the first step in fatty acid synthesis+ an anabolic process that would be stimulated by insulin+ not glucagon. As its name implies+ glycogen synthase -choice C is involved in the synthesis of glycogen. 9lucagon -and epinephrine stimulate the phosphorylation and inactivation of glycogen synthase. 589)CoA reductase -choice D is the key en,yme involved in the synthesis of cholesterol. 1ince this is an anabolic process that occurs in the well)fed state+ you would e&pect it to be stimulated by insulin and inhibited by glucagon -which it is. 7yruvate kinase -choice " cataly,es the last reaction of glycolysis. Iou would e&pect it to be inhibited by glucagon -thus decreasing the amount of glucose consumption. 9lucagon promotes the phosphorylation of pyruvate kinase+ which renders it inactive.
(hich of the following inhibits the activity of acetyl)CoA carbo&ylase?
A. Citrate B. 9lucagon C. 5igh)carbohydrate+ low)fat diet D. /nsulin
"&planation'
!he correct answer is B. !he key thing to remember here is that acetyl)CoA carbo&ylase cataly,es the first and rate)limiting step of fatty acid synthesis. /f 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. /n fact+ glucagon inhibits fatty acid synthesis by a cA87)dependent phosphorylation of acetyl)CoA carbo&ylase. Conversely+ glucagon stimulates fatty acid o&idation.
Citrate -choice A is a key player in fatty acid synthesis -citrate shuttle. !herefore+ the presence of citrate would stimulate+ not inhibit+ acetyl)CoA carbo&ylase. A high)carbohydrate+ low)fat diet -choice C would stimulate+ not inhibit+ the synthesis of fatty acids. /n contrast to glucagon+ insulin -choice D is an anabolic hormone that promotes fatty acid synthesis and therefore would stimulate acetyl)CoA carbo&ylase. /t does so by dephosphorylating the en,yme.
An individual lacking the en,yme tyrosinase would be particularly predisposed to develop which of the following?
A. 9lioblastoma multiforme B. 5emangioblastoma C. 5epatoma D. 8elanoma ". enal cell carcinoma
"&planation'
!he correct answer is D. !his 4uestion is simple if you know that tyrosinase is an en,yme in the biosynthetic pathway for melanin formation from tyrosine. A lack of tyrosinase causes one form of albinism< a second form is caused by defective tyrosine uptake. 7atients with albinism are vulnerable to developing cancers of the skin of all types+ including basal cell carcinoma+ s4uamous cell carcinoma+ and melanoma. !he 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 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)carbo&yglutamate residues ". 5ydro&ylation of proline
"&planation'
!he correct answer is D. Deficiency of vitamin * produces a clotting disorder characteri,ed by an elevated prothrombin time and easy bleeding+ particularly in neonates -hemorrhagic disease of the newborn. !he biochemical basis for this hemorrhagic tendency is that glutamate residues on Factors // -!hrombin+ #//+ /;+ and ; must be converted to gamma)carbo&yglutamate residues -in a vitamin *)re4uiring reaction for optimal activity. !he conversion of homocysteine to methionine -choice A re4uires vitamin B$%. Conversion of methylmalonyl CoA to succinyl CoA -choice B re4uires vitamin B$%. Degradation of cystathionine -choice C re4uires vitamin B:. 5ydro&ylation of proline -choice " re4uires vitamin C. #itamin C deficiency can cause easy bruising+ but will not prolong the prothrombin time.
A very ill infant is admitted to the hospital. @aboratory e&amination reveals a very high serum concentration of lactic acid. /n addition to taking steps to correct the acidosis+ the attending physician prescribes thiamine. !he rationale for thiamine administration is that thiamine is converted to a coen,yme used by which of the following en,ymes?
A. @actate dehydrogenase B. 7yruvate carbo&ylase C. 7yruvate dehydrogenase D. 7yruvate kinase ". !ransketolase
"&planation'
!he correct answer is C. !hiamine is a water)soluble vitamin that is converted to the coen,yme thiamine pyrophosphate. !his coen,yme is used by pyruvate dehydrogenase to convert pyruvate to acetyl coen,yme A. /n the absence of thiamine+ pyruvate accumulates and can be converted by lactate dehydrogenase to lactate+ which is spilled in the blood causing lactic acidosis. @actate dehydrogenase -choice A produces lactate from pyruvate but does not use thiamine pyrophosphate.
1ome lactic acidosis might be produced by decreased pyruvate carbo&ylase activity -choice B+ but the en,yme re4uires biotin rather than thiamine pyrophosphate.
7yruvate kinase -choice D makes pyruvate from phosphoenolpyruvate+ but does not use thiamine pyrophosphate.
!ransketolase -choice " re4uires thiamine pyrophosphate+ but operates in another pathway -pentose phosphate pathway. Decreased transketolase activity is not associated with the development of lactic acidosis.
A :K)year)old edentulous alcoholic male who lives alone is admitted to the hospital for evaluation of a shoulder wound that is not healing well. 6n physical e&amination+ numerous ecchymoses are noted on the posterior aspect of his legs and thighs. Careful e&amination of the mans skin reveals minute hemorrhages around hair follicles and splinter hemorrhages in the nail beds. @aboratory e&amination is remarkable for a hemoglobin of $ -normal $G)$ g>d@< no other hematologic abnormalities are noted. !herapy should consist of
A. administration of factor #/// B. administration of iron C. administration of vitamin B$% D. administration of vitamin C ". administration of vitamin *
"&planation'
!he correct answer is D. !he patient described suffers from scurvy+ due to a deficiency of dietary vitamin C. Absence of vitamin C leads to impaired hydro&ylation of proline residues in the nascent procollagen chains+ leading to weakness of blood vessel walls. Clinically+ the deficiency syndrome is characteri,ed by perifollicular hemorrhages+ fragmentation of hairs+ purpura+ ecchymoses+ splinter hemorrhages+ and hemorrhages into muscle. /n patients with normal dentition+ gum changes -swelling+ bleeding+ loosening of teeth are also noted. (ithout supplementation with vitamin C+ death may eventually occur. Administration of factor #/// -choice A would be indicated for factor #/// deficiency+ which would also lead to a prolonged 7!! -partial thromboplastin time+ which was not noted. Administration of iron -choice B would be of benefit in iron)deficiency anemia+ but there is no indication of a
hypochromic+ microcytic anemia in this patient. !he anemia of scurvy is typically normochromic and normocytic+ due to bleeding. Administration of vitamin B$%-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 * -choice " would be appropriate in the setting of vitamin * deficiency+ which would produce prolongations of the prothrombin time -7!+ followed eventually by prolongation of the 7!! as the vitamin *)dependent factors -//+ #//+ /;+ ;+ protein C+ and protein 1 are depleted.
A 9uatemalan child with a history of meconium ileus is brought in to a clinic because of a chronic cough. !he 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 ". vitamin A deficiency
"&planation'
!he correct answer is ". !he child is likely suffering from cystic fibrosis. /n this disorder+ an abnormality of chloride channels causes all e&ocrine secretions to be more viscous than normal. 7ancreatic secretion of digestive en,ymes is often severely impaired+ with conse4uent steatorrhea and deficiency of fat) soluble vitamins+ including vitamin A. Cystinuria -choice A is a relatively common disorder in which a defective transporter for dibasic amino acids -cystine+ ornithine+ lysine+ arginine< C6@A leads to saturation of the urine with cystine+ which is not very soluble in urine+ and precipitates out to form stones. 5ypoglycemia -choice B is not a prominent feature of children with cystic fibrosis who are on a normal diet. 5yperglycemia may occur late in the course of the disease.
/ron deficiency anemia -choice C is not found with any regularity in children with cystic fibrosis. 1phingomyelin accumulation -choice D is generally associated with deficiency of sphingomyelinase+ as seen in Niemann)7ick disease.
/n which of the following laboratory tests would you e&pect to find the greatest disparity in reference intervals between men and -non)pregnant women?
A. 8ean corpuscular volume B. 1erum alkaline phosphatase C. 1erum ferritin D. 1erum glucose ". 1erum sodium
"&planation'
!he correct answer is C. 8en have higher reference intervals than women in tests related to iron and hemoglobin -5b concentration in blood. !he normal reference interval for 5b concentration in women is lower -$%.)$:. gm>d@ than that for men -$.3)$E.3 gm>d@ due to lower serum testosterone levels -testosterone is higher in men and stimulates erythropoiesis and blood loss during menses. Furthermore+ women normally have about G mg of iron -as ferritin in their bone marrow iron stores versus an average of $ mg of iron for men. /n the absence of inflammation+ the small circulating fraction of ferritin -choice C correlates well with ferritin stores in the bone marrow. 5ence+ men have different reference intervals for serum ferritin than do women -$3)% ng>m@ in men versus $%)$3 ng>m@ in women. !he mean corpuscular volume -choice A+ serum alkaline phosphatase -choice B+ serum glucose -choice D+ and serum sodium -choice " are similar in both se&es.
A competitive inhibitor of an en,yme will
A. alter the #ma& of the reaction B. bind to the same site as the substrate C. decrease the apparent *m for the substrate
D. decrease the turnover number ". form an irreversible comple& with the en,yme
"&planation'
!he correct answer is B. 1ubstances that reduce the activity of an en,yme are called inhibitors. eversible inhibitors bind to an en,yme but rapidly dissociate from it Lin contrast to irreversible inhibitors -choice "+ which bind tightly and dissociate very slowly from the en,ymeM. !here are several types of reversible inhibitors' Competitive inhibitors usually resemble the substrate and compete with it for binding at the active site -choice B. !hus+ increasing the concentration of substrate will decrease the percent inhibition of the en,yme. !he #ma& is unchanged+ but the *m is increased. A noncompetitive inhibitor binds with e4ual affinity to both en,yme and en,yme)substrate comple&. !his binding leads to a distortion of the substrate binding site+ so new substrate cannot bind and>or the product cannot be released. /n this kind of inhibition+ the #ma& is decreased -choice A+ but the *m is not altered. Adding more substrate will not reverse this type of inhibition. !his is the e4uivalent of decreasing the turnover number -choice D. An uncompetitive inhibitor does not bind to free en,yme+ but binds to the en,yme)substrate comple& at a site other than the catalytic site. 6nce bound by the inhibitor+ the en,yme is trapped in the en,yme) substrate comple& state until the inhibitor dissociates. /n this kind of inhibition+ the slope of the reaction -which is the ratio *m>#ma& remains the same+ but both #ma& -choice A and *m -choice C are reduced.
A K)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. 7hysical e&amination is remarkable for pulmonary rales. Chest &)ray shows biventricular dilation of the heart. Deficiency of which of the following vitamins is the most likely cause of this childs condition ?
A. Ascorbic acid B. etinol C. iboflavin
D. !hiamine ". #itamin *
"&planation'
!he correct answer is D. !hiamine deficiency is most fre4uently encountered in alcoholics and in developing countries. Deficiency of this vitamin can take several forms' dilated cardiomyopathy -ld4uo
A %)month)old child is evaluated for failure to thrive. As the pediatrician is e&amining the child+ a convulsion occurs. 1tat serum chemistries demonstrate severe hypoglycemia+ hyperlipidemia+ lactic acidosis+ and ketosis. 7hysical e&amination is remarkable for hepatomegaly+ a finding confirmed by C! scan+ which also reveals renomegaly. (hich of the following diseases best accounts for this presentation?
A. 9auchers disease B. 8cArdles disease C. Niemann)7ick disease D. 7ompes disease ". #on 9ierkes disease
"&planation'
!he correct answer is ". #on 9ierkes disease is a glycogen storage disease caused by a deficiency of glucose):)phosphatase. /t typically presents with neonatal hypoglycemia+ hyperlipidemia+ lactic acidosis+ and ketosis. Failure to thrive is common in early life< convulsions may occur due to profound hypoglycemia. !he
glycogen accumulation in von 9ierkes disease occurs primarily in the liver and kidneys+ accounting for the enlargement of these organs. 9out may develop later because of the derangement of glucose metabolism. "ven if you dont remember all of the details of the presentation of these genetic diseases+ you should be able to narrow the choices' 9auchers disease -choice A and Niemann)7ick disease -choice C are lipid storage diseases+ and would not be e&pected to produce hypoglycemia. !he other diseases are glycogen storage diseases+ but 8cArdles -choice B and 7ompes -choice D disease affect muscle rather than liver+ and would not be e&pected to produce profound hypoglycemia since the liver is the maor source for blood glucose.
An individual with megaloblastic anemia is found to have a significant folate deficiency. "rythropoiesis is hampered in this man due to his inability to perform which type of en,ymatic reaction?
A. Acyl transfer B. Carbo&ylation C. Decarbo&ylation D. 5ydro&ylation ". 8ethylation
"&planation' !he correct answer is ". Folic acid is a pteridine vitamin that e&ists as tetrahydrofolate -!5G in its
most reduced form. !5G can accept methyl+ methylene+ or formyl carbons and transfer them as methyl groups. !his function is vital in nucleotide and amino acid synthesis. 7antothenic acid is a key vitamin in acyl transfer reactions -choice A. /t forms part of coen,yme A+ which transfers acyl groups in thiol esters as acetyl CoA+ succinyl CoA+ and other acyl CoA forms. /mportant vitamins in carbo&ylation reactions -choice B include biotin and vitamin *. Biotin carries the carbo&yl group in the pyruvate carbo&ylase and acetyl CoA carbo&ylase reactions+ and vitamin * is utili,ed in post)translational carbo&ylation of amino acid residues in blood clotting factors. 6&idative decarbo&ylation reactions -choice C re4uire thiamine -vitamin B$. "&les include the pyruvate dehydrogenase and alpha)ketoglutarate dehydrogenase comple&es.
Ascorbic acid -vitamin C is a coen,yme in the hydro&ylation -choice D of lysyl and prolyl residues of collagen. A $)year)old child is suspected of having pellagra because of chronic symptoms including diarrhea+ a red scaly rash+ and mild cerebellar ata&ia. 5owever+ his diet is not deficient in protein and he appears to be ingesting ade4uate amounts of niacin. A sister has a similar problem. Chemical analysis of his urine demonstrates large amounts of free amino acids. (hich of the following is the most likely diagnosis?
A. Alkaptonuria B. Carcinoid syndrome C. "hlers)Danlos syndrome D. 5artnups disease ". 1curvy
"&planation'
!he correct answer is D. !he child has 5artnups disease. !his condition clinically resembles pellagra -2diarrhea+ dementia+ and dermatitis2+ and may be misdiagnosed as this nutritional -niacin deficiency. /n fact+ niacin therapy may actually be helpful in controlling the symptoms. !he underlying problem is a defect in the epithelial transport of neutral amino acids+ including tryptophan+ which can act as a precursor of niacin. !he defective amino acid transport leads to poor absorption of dietary amino acids as well as e&cess amino acid secretion in the urine. Alkaptonuria -choice A is characteri,ed by urine that turns black upon standing and a debilitating arthritis. Carcinoid syndrome -choice B is seen in patients with carcinoid tumor. /t is characteri,ed by episodes of flushing+ diarrhea+ hypertension+ and bronchoconstriction. "hlers)Danlos syndrome -choice C is a disease characteri,ed by abnormal collagen formation leading to very elastic skin+ oint problems+ and fragility of some blood vessels and the intestines. 1curvy -choice " is due to vitamin C deficiency. /t is characteri,ed by easy bruising and gum problems.
(hich of the following amino acids is most responsible for the buffering capacity of hemoglobin and other proteins?
A. Arginine B. Aspartic acid C. 9lutamic acid D. 5istidine ". @ysine
"&planation'
!he correct answer is D. emember that a buffer is most effective when its p*a is within the p5 range of the surrounding medium. 5istidine is the only amino acid with good buffering capacity at physiologic p5. !he imida,ole side chain of histidine has a p*a around :. and can reversibly donate and accept protons at physiologic p5. Arginine -choice A and lysine -choice " are basic amino acids with p*as of $%.3 and $.3+ respectively< at physiologic p5 both will behave as bases and accept protons. Aspartic acid -choice B and glutamic acid -choice C are acidic amino acids with p*as of appro&imately G< at physiologic p5 they will behave as acids and donate protons.
An )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. "&cessive levels of which of the following may have produced this defect?
A. Bilirubin B. Fluoride C. 7arathormone D. !hyroid hormone ". #itamin C
"&planation'
!he correct answer is B. Fluoride e&cess causes direct inury to ameloblasts+ leading to inade4uate production
