Deck 33: Nitrogen: Heme Metabolism

Question 1

A-18-year-old woman presented with 1-week of history of fever and malaise. She had mild jaundice and elevated temperature. Hemoglobin was 13.8 g/dL, leukocyte count 13 x 10⁹/L. Serum bilirubin was elevated (42 mmol/L) and contained 95% unconjugated bilirubin. Liver enzyme tests were normal. Which of the following is the most likely cause of these signs and symptoms?

A) alcohol poisoning
B) decreased glucuronyl transferase
C) increased lactate dehydrogenase
D) excessive hemolysis
E) obstruction of bile flow

Answer 1

B
EXPLANATION: Glucuronyl transferase is the enzyme that conjugates bilirubin in the liver, after which it is excreted in bile or urine. A hereditary defect in glucuronyl transferase concentration, or activity, is called Gilbert syndrome. It may lead to mild jaundice and general discomfort with typical onset in childhood or early adulthood. Alcohol poisoning leads to liver damage, and an elevation of conjugated bilirubin. Abnormalities of liver enzyme tests would be expected. Lactate dehydrogenase catalyzes the conversion of lactate to pyruvate as part of cellular energy production. Since many cells including red blood cells are rich in LDH, increased serum LDH levels could point toward excessive hemolysis, but would not be a cause for it. Although hemolysis that exceeds the capacity of the liver to clear bilirubin from serum would lead to increased unconjugated bilirubin, it is not the best choice due to the woman's normal hemoglobin (12-16 g/ dL for females). Obstruction of bile flow leads to backup of largely conjugated bilirubin in the blood stream.

Question 2

An 11-month-old male infant is presented with failure to thrive and a persistence of anemia. Blood analysis revealed levels of lead to be twice the level deemed toxic. Additional laboratory results reveal high levels of coproporphyrinogen III in the urine. In order to rapidly lower the levels of lead in the child's blood, he is placed on chelation therapy. The child recovers fully following this treatment. The symptoms observed in this child are due to the lead-induced inhibition of which of the following enzymes of heme biosynthesis?

A) d-aminolevulinic acid (ALA) dehydratase
B) d-aminolevulinic acid (ALA) synthase
C) ferrochelatase
D) porphobilinogen (PBG) deaminase
E) uroporphyrinogen decarboxylase

Answer 2

ferrochelatase

Question 3

In carrying out an assay using cultured hepatocytes you find that addition of hemin (Fe³⁺ heme) does not have the expected consequence of reduced protoporphyrin IX synthesis. This result suggests that your hepatocytes harbor a mutant form of one of the heme-regulated enzymes of porphyrin biosynthesis. Which of the following represents the likely enzyme?

A) ALA dehydratase
B) ALA synthase
C) ferrochelatase
D) heme oxygenase
E) PBG deaminase

Answer 3

ALA synthase

Question 4

A 32-year-old man has suffered from chronic blistering and scarring of his skin following periods of unprotected exposure to sunlight. In the course of taking a history from the patient his doctor learns that the symptoms that occur following sun exposure are worse when he has been drinking heavily and smoking. The doctor orders blood and urine tests which show a high accumulation of uroporphyrin. Which of the following disorders would best explain the symptoms and clinical signs manifesting in this patient?

A) acute intermittent porphyria (AIP)
B) hereditary coproporphyria (HCP)
C) porphyria cutanea tarda (PCT)
D) variegate porphyria
E) X-linked sideroblastic anemia

Question 5

Acute intermittent porphyria (AIP) is the major autosomal dominant acute hepatic porphyria. This disease is caused by a deficiency in porphobilinogen deaminase, an enzyme of heme biosynthesis. Patients afflicted with this disease would be expected to excrete excess amounts of which of the following?

A) d-aminolevulinic acid (ALA)
B) coproporphyrinogen III
C) hydroxymethylbilane
D) protoporphyrin IX
E) type III uroporphyrinogen

Question 6

There is but a single enzyme-catalyzed reaction in the human body known to generate carbon monoxide (CO) as one of its products. Which of the following enzymes represents the one that catalyzes this CO-producing reaction?

A) biliverdin reductase
B) coproporphyrinogen oxidase
C) heme oxygenase
D) protoporphyrinogen oxidase
E) uroporphyrinogen decarboxylase

Question 7

A 9-month-old infant who suffered bouts of jaundice and was diagnosed with severe nonhemolytic icterus shortly after birth has died of kernicterus. During the periods of jaundice, serum analysis showed an increased concentration of indirectreacting bilirubin with no detection of conjugated bilirubin. The premature death and early clinical findings in this infant suggest which of the following disorders?

A) acute intermittent porphyria
B) Crigler-Najjar syndrome, type 1
C) Dubin-Johnson syndrome
D) Gilbert syndrome
E) Rotor syndrome

Question 8

An 18-month-old boy was referred to the pediatrics clinic because of persistent anemia and associated failure to thrive. Laboratory analysis confirmed a microcytic anemia and revealed blood lead levels of 50 mg/dL (2 times normal levels) and high levels of coproporphyrinogen III in the urine. The child was put on chelation therapy and recovered uneventfully. The cause of the child's difficulty was most likely due to the effects of the lead. The findings in this patient most closely reflect lead inhibition of which of the following enzymes of heme biosynthesis?

A) δ-aminolevulinic acid (ALA) dehydratase
B) ferrochelatase
C) porphobilinogen (PBG) deaminase
D) proporphyrinogen III cosynthase
E) uroporphyrinogen decarboxylase

Question 9

Which of the following represents the enzyme of porphyrin biosynthesis whose activity is negatively affected by hemin?

A) d-aminolevulinic acid dehydratase (ALA dehydratase)
B) d-aminolevulinic acid synthase (ALA synthase)
C) porphobilinogen deaminase (PBG deaminase)
D) porphobilinogen synthase
E) protoporphyrinogen IX oxidase

Question 10

An elderly homeless woman is brought to the hospital with yellowish color of her skin. From her somewhat incoherent story, it can be determined that she has consumed substantial amounts of alcohol over the past 3 decades. The physician made the diagnosis of alcoholic liver cirrhosis, associated with extensive liver fibrosis. Which of the following changes in plasma and urinary levels of bilirubin are most likely?

A) Unconjugated bilirubin in plasma: decrease
Conjugated bilirubin in plasma urine: decrease
Conjugated bilirubin in: decrease
B) Unconjugated bilirubin in plasma: decrease
Conjugated bilirubin in plasma urine: no change or increase
Conjugated bilirubin in: increase
C) Unconjugated bilirubin in plasma: increase
Conjugated bilirubin in plasma urine: decrease
Conjugated bilirubin in: increase
D) Unconjugated bilirubin in plasma: no change or increase
Conjugated bilirubin in plasma urine: increase
Conjugated bilirubin in: increase
E) nothing

Question 11

A 37-year-old woman visits her primary care physician after developing jaundice and scleral icterus. She is diagnosed with paroxysmal nocturnal hemoglobinuria. Which of the following metabolites would you expect to be increased in her urine?

A) bile
B) conjugated bilirubin
C) stercobilin
D) unconjugated bilirubin
E) urobilinogen

Question 12

A 20-year-old woman admits herself to the emergency room with a yellow discoloration of the whites of her eyes. She says that she does not drink and that she has not experienced any changes in her stool. Her liver enzyme profile and direct serum bilirubin levels are normal, while total bilirubin is elevated. What is the most likely cause for her jaundice?

A) defect in hepatocytes
B) defect in Kupffer cells
C) gallstones
D) hemolysis
E) tumor obstructing bile duct

Question 13

You are attending to a 47-year-old male patient who complains of chronic fatigue and persistent abdominal discomfort. Examination of the patient shows mildly icteric sclera and blood work indicates that serum bilirubin levels are 3 mg/dL. The bilirubin is predominantly unconjugated. The signs and symptoms in this patient are most likely due to which of the following disorders?

A) acute intermittent porphyria
B) Crigler-Najjar syndrome, type 1
C) Dubin-Johnson syndrome
D) Gilbert syndrome
E) Rotor syndrome

Question 14

You are treating a 5-day-old infant who is suffering from severe jaundice with serum indirect bilirubin levels of 21 mg/dL. Given the age of onset and the severity of the hyperbilirubinemia in this infant, which of the following would represent the most likely diagnosis?

A) acute intermittent porphyria
B) Crigler-Najjar syndrome, type 1
C) Dubin-Johnson syndrome
D) Gilbert syndrome
E) Rotor syndrome

Question 15

A 35-year-old male patient goes to the ER because he is troubled by his chronic fatigue and persistent abdominal discomfort. Additional signs in this patient are mildly icteric sclera. The ER attending calls for blood workup for bilirubin which shows the predominantly unconjugated form at a level of 2 mg/dL. The physician suspects the patient has Gilbert syndrome. Which of the following enzymes would be expected to be found at reduced levels if this is the correct diagnosis?

A) d-aminolevulinic acid synthase (ALA synthase)
B) ferrochelatase
C) heme oxygenase
D) porphobilinogen deaminase (PBG deaminase)
E) UDP-glucuronyltransferase

Question 16

Which of the following represents the most common form of hepatic porphyria?

A) acute intermittent porphyria
B) ALA dehydratase-deficient porphyria
C) hereditary coproporphyria
D) porphyria cutanea tarda type I
E) variegate porphyria

Question 17

A 23-year-old man is seen by his physician complaining of weakness, abdominal pain, nausea, and hair loss. Laboratory studies indicate hypochromic and microcytic anemia and iron overload. Histological examination of the patients' blood shows iron deposits around perinuclear mitochondria. Which of the following is the correct diagnosis for this patient?

A) acute intermittent porphyria
B) erythropoietic porphyria
C) porphyria cutanea tarda type I
D) variegate porphyria
E) X-linked sideroblastic anemia

Question 18

A 7-year-old boy is being examined to determine the cause of his severe skin blistering upon mild exposure to the sun. His parents also note that when he doesn't flush the toilet after urinating, his urine turns a very dark reddish-orange. Physical examination shows the child has darkly stained teeth and fine hairs over his entire face, arms, and legs. Blood and urine studies show high levels of uroporphyrinogen I in both and high coproporphyrinogen I in the blood. Which of the following most likely explains the signs and symptoms in the child?

A) defective bilirubin UDP-glucuronyltransferase
B) deficiency in ALA synthase
C) deficiency in uroporphyrinogen III synthase
D) enhanced activity of PBG deaminase
E) lead-induced inhibition of ALA dehydratase

Question 19

Hemin is heme with oxidized ferric (Fe³⁺) iron. This compound is known to interfere with the synthesis of the porphyrins and heme. Which of the following enzymes is inhibited by the presence of hemin?

A) ALA dehydratase
B) ALA synthase
C) ferrochelatase
D) PBG deaminase
E) uroporphyrinogen III synthase

Question 20

A 28-year-old pregnant woman is concerned about the yellowing of her eyes and skin and goes to see her obstetrician. Blood work shows mildly elevated levels of direct-reacting bilirubin. Analysis of her urine shows significant amounts of coproporphyrin I. Which of the following disorders most likely explains the signs and symptoms in this patient?

A) acute intermittent porphyria
B) Crigler-Najjar syndrome, type 1
C) Dubin-Johnson syndrome
D) Gilbert syndrome
E) Rotor syndrome

Question 21

A 2-year-old boy is brought to the physician because he developed blistering sunburn after a 15-miute exposure. His parents say that he has always burned easily. Examination shows photophobia, anemia, and splenomegaly. The urine stains in his diaper are pink to dark brown. The most likely cause of these symptoms is a defect in which of the following biosynthetic pathways?

A) cholesterol
B) ganglioside
C) glycogen
D) porphyrin
E) ubiquinone

Question 22

The rate-limiting step in the biosynthesis of heme is catalyzed by the mitochondrial enzyme d-aminolevulinic acid synthase (ALAS) from which of the following substrates?

A) acetyl-CoA and alanine
B) acetyl-CoA and glycine
C) adenine and glycine
D) succinyl-CoA and glycine
E) succinyl-CoA and GTP

Question 23

Which of the following is a product of heme degradation?

A) hemin
B) porphobilinogen
C) protoporphyrin
D) urobilinogen
E) uroporphyrinogen III

Question 24

A 3-day-old full-term male newborn is brought to the physician by his mother because of a 24-hour history of yellow skin. He appears healthy. Physical examination shows mild jaundice. Laboratory studies show a hemoglobin concentration of 17 g/ dL and a total serum bilirubin concentration of 10 mg/dL, with an indirect component of 8 mg/dL. The jaundice resolves 5 days later. A deficiency of which of the following is the most likely cause of the jaundice in this patient?

A) erythrocyte glucose6-phosphate dehydrogenase activity
B) erythrocyte pyruvate kinase activity
C) glutathione synthetase activity
D) hepatic excretion of bilirubin
E) hepatic UDP-glucuronyltransferase activity

Question 25

Bilirubin, the degradation product of heme, is only mildly water-soluble. The solubility of bilirubin in water is increased by forming a conjugate with which of the following?

A) bile acids
B) glucuronic acid
C) glycine
D) sialic acid
E) taurine