Harper's Biochemistry Chapter 31 - Porphyrins & Bile Pigments
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Questions and Answers

Which of the following is true regarding the function of cytochrome P450?

  • It catalyzes the hydroxylation of xenobiotics. (correct)
  • It is involved in oxygen storage in muscle tissues.
  • It is primarily responsible for oxygen transport in blood.
  • It mainly transports electrons in the cytoplasm.

    • What is a shared function of both hemoglobin and myoglobin?

  • They both degrade hydrogen peroxide.
  • They both catalyze the oxidation of tryptophan.
  • They are both involved in the transport of carbon dioxide.
  • They both bind and transport oxygen within different environments. (correct)

    • The effects of lead poisoning on heme synthesis can best be described as:

  • Inhibition of iron incorporation into heme. (correct)
  • Stimulating the production of cytochrome c.
  • Enhanced production of heme.
  • Increased activity of porphyrin enzymes.

    • Which metal ion is essential in the formation of heme porphyrin structures?

    <p>Iron</p> Signup and view all the answers

    Which of the following statements is accurate regarding the presence of heme proteins in cells?

    <p>Most mammalian cells produce heme, with exceptions in certain tissues.</p> Signup and view all the answers

    What specific role does ALA synthase play in heme biosynthesis?

    <p>It facilitates the first step in heme synthesis by combining Succinyl-CoA and Glycine.</p> Signup and view all the answers

    Which metabolic disorder is directly associated with mutations in the gene encoding enzyme 1 of heme synthesis?

    <p>X-linked sideroblastic anemia</p> Signup and view all the answers

    How does lead poisoning affect the heme synthesis pathway?

    <p>It inhibits the activity of ALA dehydratase and ferrochelatase by binding to essential thiol groups.</p> Signup and view all the answers

    Elevated levels of which of the following substances can be indicative of a metabolic block in heme synthesis?

    <p>Protoporphyrin and ALA</p> Signup and view all the answers

    Which of the following statements about porphyrias is true?

    <p>Porphyrias can result from both genetic and acquired causes.</p> Signup and view all the answers

    What is the implication of identifying intermediates that accumulate prior to a metabolic block in heme synthesis?

    <p>They provide a basis for metabolic screening tests to identify the impaired reaction.</p> Signup and view all the answers

    Which enzyme is responsible for catalyzing the conversion of 2-aminolevulinic acid (ALA) to porphobilinogen?

    <p>ALA dehydratase</p> Signup and view all the answers

    Which of the following metals can significantly inhibit heme synthesis by complexing with essential thiol groups?

    <p>Lead</p> Signup and view all the answers

    What is the primary consequence of mutations in genes involved in heme synthesis?

    <p>Accumulation of heme precursors</p> Signup and view all the answers

    Which substance may help patients with photosensitivity by reducing free radical production?

    <p>β-carotene</p> Signup and view all the answers

    In the catabolism of heme in human adults, what approximate weight of hemoglobin is turned over daily?

    <p>6 g</p> Signup and view all the answers

    What effect does lead poisoning have on heme synthesis?

    <p>Inhibits ALAS1 synthesis</p> Signup and view all the answers

    What is the primary underlying mechanism when ALA and PBG accumulate due to heme synthesis disorders?

    <p>Decreased heme synthesis</p> Signup and view all the answers

    How do porphyrinogens in skin relate to neurological symptoms?

    <p>They increase oxidative stress</p> Signup and view all the answers

    What is one function of heme proteins that may be impaired due to heme synthesis disorders?

    <p>Oxygen transport</p> Signup and view all the answers

    What is the consequence of spontaneous oxidation of porphyrinogens?

    <p>Compounds leading to photosensitivity</p> Signup and view all the answers

    Which of the following is not a result of heme catabolism?

    <p>Decreased erythrocyte life span</p> Signup and view all the answers

    What is the optical property associated with hematoporphyrin that is potentially useful in medical applications?

    <p>Visible light absorption</p> Signup and view all the answers

    What is the primary substrate for the synthesis of ALA in heme biosynthesis?

    <p>Glycine and succinyl-CoA</p> Signup and view all the answers

    What is the effect of phenobarbital on heme biosynthesis?

    <p>It triggers enhanced synthesis of ALAS1.</p> Signup and view all the answers

    What indicates intrahepatic or posthepatic obstructive jaundice in urinary analysis?

    <p>Presence of conjugated bilirubin with absence of urobilinogen</p> Signup and view all the answers

    Which enzyme is not regulated by heme levels?

    <p>ALAS2</p> Signup and view all the answers

    What is the major site of expression for inherited porphyrias?

    <p>Erythrocytes and liver</p> Signup and view all the answers

    Which of the following conditions is associated with the increased production of urobilinogen?

    <p>Hemolytic jaundice</p> Signup and view all the answers

    Lead poisoning can lead to which type of porphyria?

    <p>Acquired porphyrias</p> Signup and view all the answers

    Which symptom is commonly associated with porphyrias?

    <p>Photosensitivity and neurologic problems</p> Signup and view all the answers

    What is the implication of a complete obstruction of the bile duct on bilirubin levels?

    <p>Elevated levels of bilirubin without access to the intestine</p> Signup and view all the answers

    What color change is observed in urine during hemolytic jaundice?

    <p>Light yellow due to urobilinogen</p> Signup and view all the answers

    What structural difference exists between heme c and heme b?

    <p>Heme c is linked to an apoprotein through covalent thioether links.</p> Signup and view all the answers

    Which of the following intermediates are essential in heme biosynthesis?

    <p>Succinyl-CoA and glycine</p> Signup and view all the answers

    In what way do porphyrins interact with metal ions?

    <p>Porphyrins form complexes with metal ions through coordinate covalent bonds.</p> Signup and view all the answers

    Which of the following diseases may cause jaundice, resulting from elevated plasma bilirubin levels?

    <p>Hemolytic anemias</p> Signup and view all the answers

    What is a notable characteristic of vertebrate heme proteins regarding heme binding?

    <p>They generally bind one mole of heme c per mole of protein.</p> Signup and view all the answers

    What aspect of heme c synthesis distinguishes it from other heme forms?

    <p>Association with an apoprotein for functionality.</p> Signup and view all the answers

    What process is affected by lead poisoning that influences heme synthesis?

    <p>Inhibition of certain enzymes involved in porphyrin metabolism</p> Signup and view all the answers

    Which statement about porphyrin ring structure is accurate?

    <p>The structure is formed by linking four pyrrole rings through methine bridges.</p> Signup and view all the answers

    What is a common function of heme proteins in biological systems?

    <p>Participating in electron transport and redox reactions</p> Signup and view all the answers

    Which of the following statements about the side chains of porphyrins is incorrect?

    <p>All porphyrins must have the same side chains for identical function.</p> Signup and view all the answers

    What does the presence of conjugated bilirubin in urine indicate?

    <p>Intrahepatic or posthepatic obstructive jaundice</p> Signup and view all the answers

    Which enzyme is primarily responsible for the regulation of heme biosynthesis?

    <p>ALAS1</p> Signup and view all the answers

    What is the likely outcome in the urine of a patient with hemolytic jaundice?

    <p>Increased levels of both bilirubin and urobilinogen</p> Signup and view all the answers

    How does phenobarbital influence heme biosynthesis?

    <p>It triggers increased synthesis of ALAS1.</p> Signup and view all the answers

    Which statement is true regarding the inheritance of porphyrias?

    <p>Genetic abnormalities can occur in several enzymes involved in heme biosynthesis.</p> Signup and view all the answers

    What biochemical findings are markedly increased in cases of hereditary coproporphyria?

    <p>Urinary ALA, PBG, and coproporphyrin III</p> Signup and view all the answers

    Which enzyme deficiency is associated with variegate porphyria?

    <p>Protoporphyrinogen oxidase</p> Signup and view all the answers

    Which symptom is most characteristically associated with protoporphyria?

    <p>Photosensitivity</p> Signup and view all the answers

    What condition is characterized by elevated fecal protoporphyrin IX?

    <p>Protoporphyria</p> Signup and view all the answers

    Which of the following statements about photosensitivity in porphyrias is incorrect?

    <p>It leads to neuropsychiatric symptoms in all types.</p> Signup and view all the answers

    What factor influences enzyme translocation between cellular compartments in porphyrias?

    <p>Metabolic block in heme synthesis</p> Signup and view all the answers

    Which of the following conditions is considered rare compared to the others in the context of porphyrias?

    <p>Variegate porphyria</p> Signup and view all the answers

    Which enzyme is referred to as PBG deaminase?

    <p>Protoporphyrinogen oxidase</p> Signup and view all the answers

    Which of these porphyrias reflects a low or absent activity of enzymes in heme synthesis?

    <p>Hereditary coproporphyria</p> Signup and view all the answers

    What is the major cause of kernicterus related to bilirubin?

    <p>Retention hyperbilirubinemia involving unconjugated bilirubin</p> Signup and view all the answers

    Which form of bilirubin can be found in urine?

    <p>Conjugated bilirubin</p> Signup and view all the answers

    How do intestinal bacteria affect bilirubin in the gastrointestinal tract?

    <p>They reduce conjugated bilirubin to urobilinogen</p> Signup and view all the answers

    Which form of hyperbilirubinemia is associated with biliary obstruction?

    <p>Regurgitation hyperbilirubinemia</p> Signup and view all the answers

    What primarily causes jaundice in Dubin-Johnson syndrome?

    <p>Increased levels of conjugated bilirubin in the bloodstream</p> Signup and view all the answers

    What role do hepatocyte proteins play in bilirubin metabolism?

    <p>They prevent the efflux of bilirubin into the bloodstream</p> Signup and view all the answers

    What is a characteristic feature of acholuric jaundice?

    <p>Presence of excess unconjugated bilirubin in blood</p> Signup and view all the answers

    Which bilirubin type is unable to cross the blood-brain barrier?

    <p>Conjugated bilirubin</p> Signup and view all the answers

    What is indicated by the presence of choluric jaundice?

    <p>Presence of conjugated bilirubin in urine</p> Signup and view all the answers

    What is the primary purpose of conjugating bilirubin with glucuronic acid?

    <p>To increase its polarity and solubility in water</p> Signup and view all the answers

    Which of the following statements best describes the role of glutathione S-transferase in bilirubin metabolism?

    <p>It prevents bilirubin from re-entering the bloodstream</p> Signup and view all the answers

    What type of drugs should be avoided in patients with porphyria?

    <p>Drugs that induce cytochrome P450 production</p> Signup and view all the answers

    How does bilirubin's binding to albumin affect its disposition in the body?

    <p>It prevents its diffusion into tissues</p> Signup and view all the answers

    What is the effect of administering large amounts of carbohydrates in the context of porphyrias?

    <p>It decreases bilirubin production</p> Signup and view all the answers

    What is the consequence of bilirubin not being conjugated in the liver?

    <p>It will remain unbound in the bloodstream and tissues</p> Signup and view all the answers

    What role does the facilitated transport system play in bilirubin metabolism?

    <p>It assists in the uptake of bilirubin into cells</p> Signup and view all the answers

    What happens to the metabolic rate of bilirubin when there are pathological conditions affecting transport?

    <p>It remains unaffected even in pathological states</p> Signup and view all the answers

    What is a characteristics of bilirubin that necessitates its conversion to a more polar form?

    <p>Bilirubin is nonpolar and lipophilic</p> Signup and view all the answers

    What is the role of cytosolic proteins in bilirubin metabolism?

    <p>They prevent bilirubin from diffusing out of cells</p> Signup and view all the answers

    What is the role of uroporphyrinogen decarboxylase in heme biosynthesis?

    <p>It decarboxylates uroporphyrinogen to yield methyl substituents.</p> Signup and view all the answers

    What structural transformation occurs when uroporphyrinogen III undergoes decarboxylation?

    <p>Conversion to coproporphyrinogen III along with the release of CO2.</p> Signup and view all the answers

    In what cellular compartment do the final three reactions of heme biosynthesis occur?

    <p>Mitochondria.</p> Signup and view all the answers

    Why are porphyrinogens colorless, despite the presence of double bonds?

    <p>They lack a conjugated double bond system.</p> Signup and view all the answers

    What happens to porphyrinogens over time, leading to the formation of colored compounds?

    <p>They readily auto-oxidize to colored porphyrins.</p> Signup and view all the answers

    Which of the following correctly describes the relationship between uroporphyrinogen I and uroporphyrinogen III in heme biosynthesis?

    <p>Uroporphyrinogen I can also be converted to coproporphyrinogen I.</p> Signup and view all the answers

    What is the chemical byproduct of the decarboxylation of uroporphyrinogen III?

    <p>Carbon dioxide.</p> Signup and view all the answers

    Match the type of heme with its main characteristic:

    <p>Heme b = Readily dissociates from its apoprotein Heme c = Contains covalent thioether links to an apoprotein Heme a = Involved in cytochrome c oxidase Heme d = Found in some bacterial heme proteins</p> Signup and view all the answers

    Match the condition with its cause regarding jaundice:

    <p>Hemolytic anemia = Overproduction of bilirubin Viral hepatitis = Failure of bilirubin excretion Pancreatic cancer = Elevated plasma bilirubin levels Obstructive jaundice = Intrahepatic bile duct obstruction</p> Signup and view all the answers

    Match the component with its role in heme biosynthesis:

    <p>Succinyl-CoA = Provides a carbon skeleton Glycine = A key amino acid for heme synthesis ALA (Aminolevulinic acid) = First committed step in heme production Porphobilinogen = Intermediate in porphyrin synthesis</p> Signup and view all the answers

    Match the type of porphyrin with its property:

    <p>Cyclic compounds = Formed by linked pyrrole rings Metal complexes = Bind metal ions in solution Side chains = Replace hydrogen atoms on pyrroles Methyne bridges = Connect pyrrole units in porphyrins</p> Signup and view all the answers

    Match the heme-related protein with its characteristic:

    <p>Cytochrome P450 = Involved in drug metabolism Hemoglobin = Transports oxygen in blood Myoglobin = Stores oxygen in muscles Catalase = Decomposes hydrogen peroxide</p> Signup and view all the answers

    Match the enzyme involved in porphyrin metabolism with its associated condition:

    <p>ALA synthase 2 (ALAS2) = X-linked sideroblastic anemia ALA dehydratase = ALA dehydratase deficiency Uroporphyrinogen I synthase = Acute intermittent porphyria Uroporphyrinogen III synthase = Congenital erythropoietic porphyria</p> Signup and view all the answers

    Match the laboratory test results with their corresponding major signs and symptoms:

    <p>Red cell counts and hemoglobin decreased = Anemia Urinary ALA and coproporphyrin III increased = Abdominal pain, neuropsychiatric symptoms Urinary ALA and PBG increased = Abdominal pain, neuropsychiatric symptoms Urinary uroporphyrin I increased = Photosensitivity</p> Signup and view all the answers

    Match the porphyria type with its enzyme involvement:

    <p>X-linked sideroblastic anemia = ALA synthase 2 (ALAS2) Porphyria cutanea tarda = Uroporphyrinogen decarboxylase Acute intermittent porphyria = Uroporphyrinogen I synthase Congenital erythropoietic porphyria = Uroporphyrinogen III synthase</p> Signup and view all the answers

    Match the metabolic disorder with its OMIM number:

    <p>X-linked sideroblastic anemia = OMIM 301300 ALA dehydratase deficiency = OMIM 125270 Acute intermittent porphyria = OMIM 176000 Congenital erythropoietic porphyria = OMIM 263700</p> Signup and view all the answers

    Match the major symptoms with their respective types of porphyria:

    <p>Anemia = X-linked sideroblastic anemia Photosensitivity = Porphyria cutanea tarda Neuropsychiatric symptoms = Acute intermittent porphyria</p> Signup and view all the answers

    Study Notes

    Porphyrins and Bile Pigments

    • Porphyrins are cyclic compounds formed by linking four pyrrole rings through methyne bridges.
    • Heme is synthesized from porphyrins and iron.
    • Bile pigments and iron are products of heme degradation.
    • Porphyrias are diseases arising from abnormalities in porphyrin biosynthesis.
    • Jaundice is a clinical condition caused by elevated plasma bilirubin, resulting from either overproduction of bilirubin or failure of its excretion.
    • Hemes are tetrapyrroles, often b or c, with varied functions like oxygen transport and storage (hemoglobin, myoglobin), and electron transport (cytochromes).
    • Heme b has vinyl groups, while heme c is covalently linked to an apoprotein.
    • Heme synthesis occurs in most mammalian cells, primarily in erythroid precursor cells of bone marrow (~85%) and hepatocytes.
    • Heme synthesis begins with the condensation of succinyl-CoA and glycine, a pyridoxal phosphate-dependent reaction, catalyzed by mitochondrial 6-aminolevulinate synthase (ALA synthase).
    • ALA dehydratase (porphobilinogen synthase, EC 4.2.1.24) condenses two molecules of ALA into porphobilinogen.
    • ALA dehydratase is a zinc metalloprotein susceptible to lead inhibition.
    • Hydroxymethylbilane synthase (uroporphyrinogen I synthase) condenses four molecules of porphobilinogen to form the linear tetrapyrrole hydroxymethylbilane.
    • Uroporphyrinogen III synthase converts the linear hydroxymethylbilane to uroporphyrinogen III.
    • Uroporphyrinogen III undergoes decarboxylation to form coproporphyrinogen III, a reaction catalyzed by uroporphyrinogen decarboxylase.
    • Coproporphyrinogen III is converted to protoporphyrinogen III, and then to protoporphyrin III through mitochondrial reactions.
    • Ferrochelatase (heme synthase) incorporates iron into protoporphyrin III, forming heme.
    • Porphyrins and porphyrinogens are different; porphyrinogens are colorless while porphyrins are colored, due to the conjugated system in porphyrins.
    • Porphyrins and their precursors are detected through spectrophotometry, measuring their absorption/fluorescence spectra.
    • Porphyrias result from defects in specific enzymes in heme synthesis leading to accumulation of porphyrin precursors, causing clinical symptoms.
    • Some types are acute intermittent porphyria, congenital erythropoietic porphyria.

    Heme Biosynthesis

    • Heme synthesis involves both cytosolic and mitochondrial reactions.
    • Heme synthesis occurs in most mammalian cells except mature erythrocytes.
    • ALA synthase (ALAS1) is the rate-limiting enzyme in hepatic porphyrin synthesis, regulated by heme.

    Catabolism of Heme

    • Heme is degraded, primarily in reticuloendothelial cells of the liver, spleen, and bone marrow.
    • Heme oxygenase (EC 1.14.18.1) catalyzes the degradation of heme.
    • Heme oxygenase converts heme to biliverdin and carbon monoxide (releasing iron), requiring oxygen and electrons from NADH/NADPH.
    • Biliverdin reductase reduces biliverdin to bilirubin.
    • Bilirubin is transported to the liver bound to serum albumin.
    • Bilirubin is conjugated with glucuronide, becoming water-soluble.
    • Conjugated bilirubin is secreted into bile.
    • Intestinal bacteria convert conjugated bilirubin to urobilinogen.
    • Urobilinogen is converted to urobilin, excreted in feces.
    • Some urobilinogen is reabsorbed and returned to the liver, completing the enterohepatic cycle.

    Disorders of Bilirubin Metabolism

    • Neonatal physiologic jaundice: Immature hepatic system for bilirubin uptake/conjugation/secretion.
    • Gilbert syndrome: Reduced bilirubin UDP-glucuronosyltransferase activity.
    • Crigler-Najjar syndrome (types I and II): Absent or reduced bilirubin UDP-glucuronosyltransferase activity, resulting in severe hyperbilirubinemia and potential neurological damage.
    • Obstructive jaundice: Blockage of bile ducts, causing conjugated bilirubin to accumulate in the blood, leading to characteristic symptoms and lab test results.
    • Toxic hyperbilirubinemia: Toxin-induced liver dysfunction, resulting in impaired bilirubin conjugation.

    Hyperbilirubinemia

    • Hyperbilirubinemia (excess bilirubin in the blood) causes jaundice (yellowing of tissues).
    • Hyperbilirubinemia arises from increased bilirubin production or impaired liver function.
    • Unconjugated and conjugated hyperbilirubinemia have different clinical presentations due to the different pathways of excretion.

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    Description

    This quiz delves into the structure and function of porphyrins, their role in heme synthesis, and the clinical conditions associated with bile pigments. It covers essential concepts like porphyrias, jaundice, and the biological significance of heme in mammals. Test your understanding of these complex biochemical processes and their implications for health.

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