biochem - block 03

A 6-month-old boy is brought to the emergency department by his mother because of recurrent vomiting and yellowing of his eyes. The mother says that he has been eating poorly since she started weaning him off of breast milk 5 days ago. At this time, mashed vegetables and fruits were added to his diet.

Examination shows scleral jaundice and dry mucous membranes. The tip of the liver is palpable 4 cm below the right costal margin. His serum glucose concentration is 47 mg/dL, serum alanine aminotransferase is 55 U/L, and serum aspartate aminotransferase is 66 U/L.

Which of the following enzymes is most likely deficient?

aldolase B

A 59-year-old man comes to the physician because of bilateral blurry vision and difficulty driving at night that has been worsening progressively over the past 5 months. He has hypertension, type 2 diabetes mellitus, and hyperlipidemia. His hemoglobin A1c concentration is 8.9%. A slit-lamp shows cloudy opacities of the lenses bilaterally.

The patient's eye condition is most likely due to increased activity of which of the following enzymes?

aldose reductase

A 12-month-old boy is brought to the physician by his mother for a well-child examination. He was delivered at term after an uncomplicated pregnancy. His mother says he is breastfeeding well. He is at the 50th percentile for height and 65th percentile for weight. Physical examination shows no abnormalities. Urinalysis shows 3+ reducing substances.

Compared to a healthy infant, giving this patient apple juice to drink will result in increased activity of which of the following enzymes?

hexokinase

A 22-year-old man comes to the physician for a routine physical examination. He feels well. He has no history of major medical illness and takes no medications. His vital signs are within normal limits. Examination shows no abnormalities.

Laboratory studies, including a complete blood count and a standard electrolyte panel, are within normal limits. Urine dipstick is negative for glucose; a reducing substance test result of the urine is positive.

Which of the following is the most appropriate dietary recommendation for this patient?

no changes needed

A 2-year-old boy with recurrent ear infections is brought to the pediatrician for a follow-up examination. He can walk with support and his vocabulary consists of approximately 50 words. His maternal uncle died in childhood from an unknown disease.

Physical examination shows coarse facial features with an enlarged tongue. The abdomen is distended and both the liver and spleen tip are palpable.

Laboratory studies show elevated total urinary glycosaminoglycan levels and an absence of plasma iduronate-2-sulfatase.

Which of the following additional findings is most likely in this patient?

aggressive behavior

A 7-day-old female newborn is brought to the physician because of lethargy, vomiting, poor feeding, and diarrhea for 4 days. She was born at 39 weeks' gestation. Vital signs are within normal limits. Bilateral cataracts and icterus are present. Examination shows jaundice of the skin, and the liver is palpated 5-cm below the right costal margin. Muscle tone is decreased in all extremities. Serum glucose concentration is 40 mg/dL.

Which of the following metabolites is most likely to be increased in this patient?

galactose-1-phosphate

A 6-month-old boy is brought to the physician for the evaluation of developmental delay. His mother reports that he babbles and turns his attention to her when she calls his name but she is concerned because he has never smiled and does not seem to recognize her face. He is exclusively breastfed and at the 60th percentile for height and 85th percentile for weight.

Ophthalmological examination shows a white reflex in both eyes and a failure to track the penlight. During the examination, he sits without support and grasps toys that are placed in his hand. A reducing substance test result of the urine is positive, and a glucose oxidase test result is negative.

This patient is most likely deficient in an enzyme that catalyzes which of the following labeled reactions?

C

A 26-year-old African American man comes to the physician because of a 3-day history of fatigue, back pain, and dark urine. One week ago, he developed a headache and was treated with aspirin. He does not smoke or use illicit drugs.

Physical examination shows conjunctival pallor. A peripheral blood smear shows erythrocytes with inclusions of denatured hemoglobin.

Which of the following enzymes is essential for the production of nucleotides in this patient?

transketolase

An investigator is studying biomolecular mechanisms in human cells. A radioactive isotope that is unable to cross into organelles is introduced into a sample of cells. The cells are then fragmented via centrifugation and the isotope-containing components are isolated. .

Which of the following reactions is most likely to be present in this cell component?

glucose-6-phosphate → 6-phosphogluconolactone

A 2-year-old boy is brought to the pediatrician for evaluation of recurrent falls and clumsiness. He can only walk with support, and his vocabulary consists of approximately 20 words. He cannot hold objects or stack blocks.

Physical examination shows coarse facial features and scoliosis. A holosystolic murmur is heard at the apex. The abdomen is distended, and both the liver and spleen tips are palpable. Fundoscopic examination shows cloudy corneas.

Laboratory studies show complete inactivity of the N-acetylglucosaminyl-1-phosphotransferase enzyme.

This condition is most likely associated with an accumulation of which of the following substances in the patient's serum?

lysosomal phosphatase

A 4-year-old girl is brought to the physician by her mother because of fatigue and generalized weakness for 4 months. Examination shows decreased muscle tone. Her fasting serum glucose concentration is 41 mg/dL. The physician suspects a defect in one of the enzymes involved in the carnitine shuttle.

Increased serum concentration of which of the following would be inconsistent with this diagnosis?

β-hydroxybutyrate

A 6-month-old girl is brought to the emergency department by her father after he observed jerking movements of her arms and legs earlier in the day. She appears lethargic. Physical examination shows generalized hypotonia. The liver edge is palpable 3 cm below the right costophrenic angle.

Her fingerstick glucose shows hypoglycemia. Serum levels of acetone, acetoacetate, and β-hydroxybutyrate are undetectable. Molecular genetic testing shows a mutation in the carnitine palmitoyltransferase I gene.

This patient will most likely benefit from supplementation with which of the following?

medium-chain triglycerides

A 15-year-old girl who had been diagnosed with cystic fibrosis at age 8 has recently begun losing weight. She complains of fatigue and large, foul-smelling stools.

A deficiency in the activity of which of the following enzymes is most likely the cause of her symptoms? 

pancreatic lipase

An 11-month-old boy with cystic fibrosis is brought to the physician by his parents for a 3-week history of bulky, oily, foul-smelling stools. He is at the 5th percentile for height and 6th percentile for weight. Physical examination shows sparse hair growth and a generalized dry, scaly rash. A diagnosis of essential fatty acid deficiency is made.

Which of the following is a direct derivative of an essential fatty acid that is most likely to be insufficiently absorbed in this patient?

arachidonic acid

A 10-month-old boy with a seizure disorder is brought to the physician by his mother because of a 2-day history of vomiting and lethargy. Laboratory studies show a decreased serum glucose concentration. Further testing confirms a deficiency in an enzyme involved in lipid metabolism that is found in the liver but not in adipose tissue.

Which of the following enzymes is most likely deficient in this patient?

glycerol kinase

Television personality Dr. Oz claims that extracts of garcinia cambogia, a tamarind-like fruit grown in Southeast Asia, are a “magic” weight loss aid. The active ingredient is hydroxycitrate, which inhibits citrate lyase.

Which of the following best explains how the extract might promote weight loss? 

it inhibits conversion of dietary carbohydrates to fatty acids

An 8-year-old boy with a history of epilepsy that is not well controlled pharmaceutically is placed on a special diet that is sometimes therapeutic in epileptic patients. After 2 weeks on the diet, the boy’s serum ketone levels are about 10 times higher than they were before he started the diet.

Which of the following enzyme activities is most likely stimulated in this patient?

hormone sensitive lipase 

A 15-year-old boy is brought to the emergency department by his parents because of lethargy, repeated vomiting, and abdominal pain for 6 hours. Over the past 2 weeks, he has reported increased urinary frequency to his parents that they attributed to his increased oral fluid intake. Examination shows dry mucous membranes and rapid, deep breathing. Laboratory studies show the presence of acetoacetate in the urine.

Which of the following cells is unable to use this molecule for energy production?

hepatocyte

A 4-month-old boy is brought to the emergency department by his mother because of lethargy and vomiting since he woke up 1 hour ago. The mother says that he last breastfed the previous evening and slept through the night for the first time. His family recently immigrated from Bolivia. His temperature is 38.7°C (101.7°F). Physical examination shows dry mucous membranes and enlarged, reddened tonsils.

Serum studies show:

• Glucose 42 mg/dL

• Ketones 0.1 mg/dL (N ≤ 1)

• AST 76 U/L

• ALT 120 U/L

• Ammonia 80 μ/dL (N = 15–45)

Which of the following enzymes is most likely deficient in this patient?

medium-chain acyl-CoA dehydrogenase

A 7-year-old boy is brought to the clinic by his parents because of progressive difficulty walking and rapid visual loss over the past 3 months. Over the past year, his teachers have noted some behavioral changes as well as worsening grades. Family history includes a maternal uncle who had similar symptoms and died when he was 9-years-old. His temperature is 37°C (98.6°F), pulse is 72/min, respirations are 22/min, and blood pressure is 78/50 mm Hg.

Examination shows hyperpigmentation of the skin. Neurologic examination shows increased tone and decreased power in all extremities. Deep tendon reflexes are 3+ bilaterally. His gait is ataxic. Blood tests show abnormally increased levels of very long chain fatty acids.

Which of the following cellular organelles is most likely affected in this patient?  

peroxisomes

A 57-year-old woman comes to the physician for a routine examination. She takes no medications. She swims 3 times weekly and jogs several miles with her dog on most mornings. Her diet consists primarily of vegetables, fish, and whole grains; she avoids processed foods and carbohydrates. She drinks one glass of red wine with dinner on most evenings. There is no family history of serious medical illness or cardiovascular disease. Physical examination shows no abnormalities.

This patient is most likely to have an increase in which of the following laboratory markers?

high density lipoprotein (HDL)

A 15-year-old male was referred to a gastroenterologist by his optometrist who was concerned that the boy exhibited signs of hypovitaminosis A. The boy reported a long history of recurrent diarrhea, producing foul-smelling, foul-smelling, non-watery stools that were difficult to flush. He also reported mild peripheral neuropathy. Physical examination revealed slight hepatomegaly. The gastroenterologist ordered a fasting lipid profile, as well as serum vitamin analysis.

The relevant laboratory results are shown below, where the image on the right was obtained. Subsequently, a biopsy of the duodenal mucosa was obtained. An image from that biopsy is shown in the right hand panel below. The image in the left panel is of normal mucosa, for comparison and the image on the left is shown for comparison (i.e., a normal tissue sample).

A mutation in the gene for which of the following proteins most likely has contributed to this patient’s symptoms?

apolipoprotein B (ApoB)

A 30-year-old woman comes to the emergency department due to severe epigastric pain that radiates to her back accompanied by nausea and vomiting. She denies consuming alcohol within the past week. Physical examination shows multiple soft, orange papules on the right posterior elbow.

Serum studies show leukocytosis and elevated levels of amylase and lipase. One of the laboratory technicians reports that a white, milky layer formed on top of the sample after centrifugation.

Which of the following proteins is most likely deficient in this patient?

apolipoprotein C-II

Lipoprotein particles were isolated from a patient with hyperlipidemia and then separated by centrifugation. Images of the particles, all at the same level of magnification, are shown in the figure below.

Which of the following most accurately indicates the identities of the various lipoprotein particles?

E

A 24-year-old male presents to his primary care physician, concerned about bumps that have been developing on his elbow over the past few months. His family history reveals that the patient’s father recently died of a heart attack at age 45.

Which of the following proteins is most likely expressed at an abnormally high levels in this patient?

HMG-CoA reductase

 9-year-old boy is brought to the physician by his mother for evaluation of diffuse bone pain in his right leg. His family immigrated to the United States 6 months ago from northern Canada. He is below the 5th percentile for height and at the 10th percentile for weight. Physical examination shows tenderness to palpation of the right distal femur. There is hepatosplenomegaly. An x-ray of right femur shows generalized trabecular thinning and several osteolytic bone lesions.

Laboratory studies show:

• Hemoglobin 9.2 g/dL

• Leukocyte count 7,600/mm3

• Platelets 71,000/mm3

A bone marrow aspirate shows mononuclear cells filled with lipid that appear like wrinkled silk.

Deficiency of which of the following enzymes is the most likely cause of this patient's symptoms?

glucocerebrosidase

A 2-year-old boy is brought to the emergency department by his parents because of fever and recurrent episodes of jerky movements of his extremities for the past 6 hours. Pregnancy and delivery were uncomplicated, and development was normal until the age of 1 year. The parents report that he has had gradual loss of speech, vision, and motor skills over the past year. During this time, he has been admitted to the hospital three times because of myoclonic seizures.

Physical examination shows hypertonicity of the upper and lower extremities. Fundoscopic examination shows pallor of the optic disc bilaterally. An MRI of the brain shows brain atrophy and hyperintensity of the periventricular and subcortical areas. Two days after admission, the patient dies. Histopathologic examination of the brain shows aggregation of globoid cells and loss of glial cells.

The patient’s condition was most likely caused by a deficiency of which of the following enzymes?

β-galactocerebrosidase

An 18-month-old boy is brought to the physician because of a 2-day history of cough, fever, and lethargy. He has been admitted to the hospital twice during the past year for pneumonia. He can stand without support but has not started to walk. He speaks in bisyllables. He is at the 3rd percentile for height and 4th percentile for weight.

Examination shows diffuse crackles over bilateral lung fields. Abdominal examination shows hepatosplenomegaly. Fundoscopy shows bright red macular spots. Despite being given appropriate antibiotic therapy, the patient dies. A photomicrograph of a section of the spleen obtained during autopsy is shown.

Accumulation of which of the following substances is the most likely cause of this patient's condition?

sphingomyelin

A 10-month-old infant girl is brought the pediatrician's office for the evaluation of developmental delay. The baby girl was prematurely born to a gravida 1, para 0, mother via cesarean section following an uncomplicated pregnancy. Medical history is relevant for low-weight and growth below the third percentile since birth and a generalized seizure  a month ago. The mother reports that the seizure  was triggered by excessive noise. The family is of Ashkenazi Jewish descent.

Her temperature is 36.4°C (97.5°F), pulse is 100/min, respirations are 16/min, blood pressure  is 120/60 mmHg. A physical exam shows a positive startle reflex, decreased alertness, and blindness. A biopsy shows lysosomes with onion skin  appearance.

A deficiency of which of the following enzyme  activities is the most likely cause of the findings in this patient? 

hexosaminidase A.

A 9-month-old girl is brought to the physician by her parents for multiple episodes of unresponsiveness in which she stares blankly and her eyelids flutter. She has gradually lost control of her neck and ability to roll over during the past 2 months. She is startled by loud noises and does not maintain eye contact.

Her parents are of Ashkenazi Jewish descent. Neurological examination shows generalized hypotonia. Deep tendon reflexes are 3+ bilaterally. Fundoscopy shows bright red macular spots bilaterally. Abdominal examination shows no abnormalities.

Which of the following metabolites is most likely to accumulate due to this patient's disease?

GM2 ganglioside

An infant who is apparently healthy at birth is diagnosed with Aldolase B deficiency two weeks later.

Which of the following biomolecule should be removed from this patient’s diet?

sucrose

A 27-year-old healthy pregnant woman demonstrates a positive dipstick reaction for sugar on routine urine screening. However, blood glucose levels were within normal limits, and more specific testing for urine glucose is negative. The woman has been unaware of any metabolic problems and has been living a normal life.

Deficiency of which of the following enzyme would most likely produce this presentation?

fructokinase

Which of the following best explains why fructose is often used as a carbohydrate substitute in special foods for patients with diabetes mellitus?

fructose has a specific kinase in liver that allows bypass of phosphofructokinase

A pediatrician examines two babies with two separate deficiencies in fructose metabolism. The first child has a deficiency of fructokinase, and the second has a deficiency of aldolase B. Although the physician states with confidence that the first child has a benign prognosis, he is concerned about the second child.

What best explains the clinical severity of aldolase B deficiency?

sequestration of phosphate

Monosaccharides delivered to the liver may have different rates of intracellular metabolism.

Which of the following substances has the shortest route of entry in the glycolytic pathway?

fructose-1-phosphate

Activity of an enzyme called aldose reductase in the lens of a healthy individual produces sorbitol that can not exit the cells.

Which of the following is the most likely product of sorbitol oxidation in these cells?

fructose

A patient was found to have elevated level of galactose in the blood, but low cellular level of galactose-1-phosphate.

Which of the following enzymes is most likely affected in this patient?

galactokinase

A woman, shortly after giving birth to her first child, was discovered to be unable to synthesize lactose. Analysis of various glycoproteins in her serum indicated that there was no defect in the carbohydrate chains nor was the carbohydrate content of her cell surface glycolipids altered.

This woman may have a mutation in which one of the following proteins or class of proteins? 

α- lactalbumin

A 7-day-old infant begins vomiting after feeding, becomes severely jaundiced, has enlargement of liver, and cloudy lenses of the eyes suggestive of cataracts. Treatment for possible sepsis is initiated, and the urine is found to have reducing substances. A blood test for galactosemia is positive, and lactose-containing substances are removed from the diet.

Galactose is toxic in this case because of which of the following?

galactose is converted to the toxic substance galactitol

A 18-year-old male with vision impairment is found to have bilateral lens opacity. He is otherwise asymptomatic and does not follow any specific diet. Laboratory evaluation reveals urinary excretion of large amounts of galactose.

Activity of which of the following enzymes most likely contributes to this patient’s eye condition?

aldose reductase

Which of the following best describes a person with galactosemia caused by a deficiency of galactose-1- phosphate uridylyltransferase?

she can form galactose 1-phosphate from galactose

A newborn appears normal at birth, but develops vomiting and diarrhea accompanied by jaundice and hepatomegaly within the first few weeks of life. Within months, the baby has obvious cataracts and ascites. The infant is switched to a milk-free diet, which stabilizes but does not completely reverse his condition.

By one year of age, he has developed mental retardation. Which of the following is the most likely diagnosis?

galactosemia

A 2-year-old boy is brought to the local emergency room with complaints of fever and diarrhea for several days. The pediatrician admits the boy for dehydration secondary to presumptive rotavirus-induced gastroenteritis. A few days after the discharge, the patient is seen again by the pediatrician for abdominal distention and diarrhea after each feeding. The symptoms improve significantly once dairy products are eliminated from his diet.

Which of the following steps in galactose metabolism is most likely impaired in this patient ?

E