Hemoglobin and Porphyria Cutanea Tarda
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Questions and Answers

Which enzyme catalyzes the formation of Aminolevulinic Acid (ALA) in the mitochondria?

  • Heme
  • ALA Synthase (correct)
  • Cytochrome
  • Porphobilinogen Deaminase

    • What inhibits ALA Dehydratase in the heme biosynthesis pathway?

  • Iron
  • Lead (correct)
  • Cytochromes
  • Heme

    • Which compound is formed by the condensation of 2 Aminolevulinic Acid (5-ALA) molecules?

  • Hydroxymethylbilane
  • Heme
  • Porphobilinogen (correct)
  • Uroporphyrinogen

    • Where does Heme Biosynthesis primarily take place?

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

    Which enzyme converts uroporphyrinogen 3 into coproporphyrinogen 3?

    <p>Uroporphyrinogen decarboxylase</p> Signup and view all the answers

    Which enzyme converts protoporphyrin IX into Heme?

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

    What is the effect of lead on Ferrochelatase?

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

    How does Heme abundance affect Pyrophin's and Nucleotide Metabolism?

    <p>Biosynthesis decreases</p> Signup and view all the answers

    Which enzyme is responsible for the phosphorylation of AMP to ADP?

    <p>Adenylate Kinase</p> Signup and view all the answers

    What is the precursor for pyridine synthesis and rapidly converted in nucleotide synthesis?

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

    Which deficiency results in Lesch-Nyhan Syndrome, characterized by neurological abnormalities and excessive uric acid production?

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

    What is the inhibitor of xanthine oxidase used in the treatment of Pyrophin's and Nucleotide Metabolism?

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

    Which enzyme deficiency results in severe combined immunodeficiency (SCID)?

    <p>Adenosine Deaminase</p> Signup and view all the answers

    What is involved in the formation of Thymidylate, essential for DNA synthesis?

    <p>$Methylenetetrahydrofolate$</p> Signup and view all the answers

    Which enzyme plays a role in the phosphorylation of GMP to GDP?

    <p>Guanylate Kinase</p> Signup and view all the answers

    Which pathway allows the body to reuse hypoxanthine and guanine by forming IMP and GMP?

    <p>Salvage pathway</p> Signup and view all the answers

    What are purine nucleotides degraded to, and excreted in what way?

    <p>Uric acid, excreted in urine</p> Signup and view all the answers

    What is oxidized to uric acid by xanthine oxidase, but can be utilized by the salvage pathway?

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

    What is involved in pyrimidine synthesis regulation and its role in forming the orotate ring?

    <p>Carbamoyl phosphate</p> Signup and view all the answers

    Which of the following is a function of nucleotides?

    <p>Energy compounds (ATP)</p> Signup and view all the answers

    What is the consequence of liver cells being unable to conjugate heme fast enough during massive hemolysis?

    <p>High unconjugated bilirubin in the bloodstream</p> Signup and view all the answers

    Which component is not part of a nucleotide structure?

    <p>Ribose sugar</p> Signup and view all the answers

    In which type of jaundice does bilirubin fail to pass into the intestine due to bile duct obstruction?

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

    What is the precursor for nucleotide triphosphates, which are essential for nucleic acid synthesis?

    <p>$PRPP$ (phosphoribosylpyrophosphate)</p> Signup and view all the answers

    'Thymine' belongs to which category of nitrogenous bases?

    <p>$Pyrimidine$</p> Signup and view all the answers

    What is the source of nucleotides through salvage pathways?

    <p>Dietary intake of preformed nucleotides</p> Signup and view all the answers

    What is the final product of purine synthesis de novo after multiple phosphorylation steps?

    <p>$Inosine Monophosphate (IMP)$</p> Signup and view all the answers

    What is the primary function of myoglobin in muscle cells?

    <p>Stores and releases oxygen for muscle use</p> Signup and view all the answers

    Which condition is characterized by the presence of abnormal hemoglobin known as HbS?

    <p>Sickle cell disease</p> Signup and view all the answers

    What is the consequence of carbon monoxide (CO) binding to hemoglobin?

    <p>It causes a shift in hemoglobin conformation from oxy to deoxy state</p> Signup and view all the answers

    What is the primary function of fetal hemoglobin (HbF) in the fetus?

    <p>Facilitates exchange between mother and fetus</p> Signup and view all the answers

    Which genetic disorder results from an insufficient amount of hemoglobin due to an imbalance in globin chain synthesis?

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

    What is the primary role of cytochrome P450 in the liver?

    <p>Detoxification and excretion of drugs/foreign substances</p> Signup and view all the answers

    What is the normal serum bilirubin level, and at what level does hyperbilirubinemia occur?

    <p>0.2-1.2 mg/dL; &gt;1.2 mg/dL</p> Signup and view all the answers

    Which enzyme catalyzes the formation of Porphobilinogen from 2 Aminolevulinic Acid (5-ALA) molecules in the heme biosynthesis pathway?

    <p>Porphobilinogen Deaminase</p> Signup and view all the answers

    What is the precursor for Heme Biosynthesis that is derived from a TCA cycle intermediate?

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

    Which enzyme deficiency results in the accumulation of porphyrins and leads to conditions such as porphyria?

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

    What is the prosthetic group in Heme, also known as Ferroprotroporphyrin, that aids enzymes in their functions?

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

    Which enzyme is responsible for the conversion of coproporphyrinogen III to protoporphyrin IX?

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

    What is the consequence of lead inhibition of ALA dehydratase and Ferrochelatase in the heme biosynthesis pathway?

    <p>Elevated ALA levels and lead-associated anemia</p> Signup and view all the answers

    What is the consequence of heme abundance on biosynthesis in the context of pyrophins and nucleotide metabolism?

    <p>Biosynthesis decreases due to heme repression of ALA synthase</p> Signup and view all the answers

    What are the features associated with enzyme defects upstream of tetrapyrroles in heme synthesis?

    <p>Abdominal pain, psychiatric, and neurologic manifestations</p> Signup and view all the answers

    Which of the following can cause prehepatic jaundice?

    <p>Abnormal hemoglobin</p> Signup and view all the answers

    What is the precursor for nucleotide triphosphates, essential for nucleic acid synthesis?

    <p>Inosine monophosphate (IMP)</p> Signup and view all the answers

    Which enzyme is involved in the phosphorylation of GMP to GDP?

    <p>Guanosine monophosphate kinase</p> Signup and view all the answers

    What can lead to a pale stool and dark urine due to bilirubin not passing into the intestine?

    <p>Intrahepatic bile duct obstruction</p> Signup and view all the answers

    What is the source of nucleotides through salvage pathways?

    <p>Preformed nucleotides in diet</p> Signup and view all the answers

    Where does Heme Biosynthesis primarily take place?

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

    What is oxidized to uric acid by xanthine oxidase, but can be utilized by the salvage pathway?

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

    What inhibits ALA Dehydratase in the heme biosynthesis pathway?

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

    Which of the following is true about the quaternary structure of hemoglobin?

    <p>Deoxy Hb (T-State) has salt bridges between alpha and beta dimers</p> Signup and view all the answers

    What is the consequence of carbon monoxide (CO) binding to hemoglobin?

    <p>Forms stronger bonds with heme compared to O2</p> Signup and view all the answers

    At what partial pressure of oxygen (PO2) is hemoglobin 75% saturated in resting muscle capillaries?

    <p>$45$ mmHg</p> Signup and view all the answers

    What occurs after birth regarding the hemoglobin composition in humans?

    <p>The gamma gene is turned off, and the beta gene is turned on</p> Signup and view all the answers

    Which genetic disorder results from an insufficient amount of hemoglobin due to an imbalance in globin chain synthesis?

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

    What enzyme plays a role in the first step of heme degradation within macrophages of the reticuloendothelial system?

    <p>Heme Oxygenase</p> Signup and view all the answers

    What is the primary function of myoglobin in muscle cells?

    <p>To store oxygen for mitochondrial use</p> Signup and view all the answers

    What is the final product of purine synthesis de novo after multiple phosphorylation steps?

    <p>Inosine Monophosphate (IMP)</p> Signup and view all the answers

    What are purine nucleotides degraded to, and how are they excreted?

    <p>Uric acid, excreted in urine</p> Signup and view all the answers

    Which enzyme is responsible for the phosphorylation of AMP to ADP and GMP to GDP?

    <p>Adenylate Kinase and Guanylate Kinase</p> Signup and view all the answers

    What is the precursor for all pyrimidine nucleotides?

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

    Which enzyme deficiency results in Lesch-Nyhan Syndrome, characterized by neurological abnormalities and excessive uric acid production?

    <p>HGPRT (Hypoxanthine-guanine phosphoribosyltransferase)</p> Signup and view all the answers

    What is the inhibitor of xanthine oxidase used in the treatment of Pyrophin's and Nucleotide Metabolism?

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

    What enzyme is involved in the formation of Thymidylate, essential for DNA synthesis?

    <p>$\text{Thymidylate Synthase}$</p> Signup and view all the answers

    What are purine nucleotides degraded to, and excreted in what way?

    <p>Uric acid, excreted in urine</p> Signup and view all the answers

    What is the final product of purine synthesis de novo after multiple phosphorylation steps?

    <p>IMP and GMP</p> Signup and view all the answers

    Which enzyme converts protoporphyrin IX into Heme?

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

    What is involved in pyrimidine synthesis regulation and its role in forming the orotate ring?

    <p>Carbamoyl phosphate synthetase II, which forms carbamoyl phosphate for pyrimidine synthesis regulation.</p> Signup and view all the answers

    What is oxidized to uric acid by xanthine oxidase, but can be utilized by the salvage pathway?

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

    Which enzyme converts uroporphyrinogen III into coproporphyrinogen III?

    <p>Uroporphyrinogen decarboxylase</p> Signup and view all the answers

    Which enzyme is responsible for the phosphorylation of AMP to ADP?

    <p>Adenylate Kinase</p> Signup and view all the answers

    What is the precursor of all pyrimidine nucleotides?

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

    What enzyme deficiency results in Lesch-Nyhan Syndrome, characterized by neurological abnormalities and excessive uric acid production?

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

    What inhibits xanthine oxidase, an enzyme involved in the oxidation of hypoxanthine to uric acid?

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

    What is the consequence of a deficiency in Adenosine Deaminase?

    <p>Severe Combined Immunodeficiency (SCID)</p> Signup and view all the answers

    Which enzyme is involved in the formation of Thymidylate, essential for DNA synthesis?

    <p>Thymidylate Synthase</p> Signup and view all the answers

    What is the final product of purine synthesis de novo after multiple phosphorylation steps?

    <p>ATP and GTP</p> Signup and view all the answers

    Which enzyme catalyzes the formation of Porphobilinogen from 2 Aminolevulinic Acid (5-ALA) molecules in the heme biosynthesis pathway?

    <p>Uroporphyrinogen III Synthase</p> Signup and view all the answers

    What are purine nucleotides degraded to, and how are they excreted?

    <p>Uric acid, excreted in urine</p> Signup and view all the answers

    Study Notes

    • AMP and GMP can be converted to ATP and GTP through phosphorylation by kinases

    • IMP is a precursor for pyridine synthesis and is rapidly converted in nucleotide synthesis

    • Nucleoside monophosphate/diphosphate kinases play a role in phosphorylation of AMP to ADP and GMP to GDP

    • Adenylate Kinase and Guanylate Kinase are the kinases responsible for the phosphorylation of AMP and GMP respectively

    • Regulation of purine biosynthesis is controlled by the concentrations of both adenine and guanine nucleotides, which affects the production of IMP

    • Purine nucleotides are degraded to uric acid and excreted in the urine

    • Hypoxanthine, a base in purine nucleotides, is oxidized to uric acid by xanthine oxidase, but can be utilized by the salvage pathway

    • The salvage pathway allows the body to reuse hypoxanthine and guanine by forming IMP and GMP

    • The inability to salvage hypoxanthine and guanine due to a deficiency in HGPRT results in Lesch-Nyhan Syndrome, which is characterized by neurological abnormalities and excessive uric acid production

    • Pyrophin's and Nucleotide Metabolism can be treated with Allopurinol, an inhibitor of xanthine oxidase, and Colchicine for acute arthritic attacks in gout

    • Adenosine Deaminase is an enzyme of purine nucleotide degradation and an autosomal recessive deficiency of this enzyme results in severe combined immunodeficiency (SCID)

    • Pyrimidine synthesis regulation involves the synthesis of carbamoyl phosphate and its role in forming the orotate ring

    • UMP is decarboxylated to form uridine, which is a precursor of all pyrimidine nucleotides

    • UMP is used to form UTP through similar synthesis as purine triphosphates

    • Methylenetetrahydrofolate is involved in the formation of Thymidylate, which is essential for DNA synthesis

    • Uridine monophosphate is the precursor of all pyrimidine nucleotides

    • Deoxyribonucleotides of Adenine, Guanine, and Cytosine are synthesized from ribonucleotides by reduction of 2-hydroxyl by ribonucleotide reductase.

    • Hepatic and Erythropoietic Porphyria Cutanea Tarda: occurs on sun-exposed hands, characterized by photosensitivity due to complement/mast cell activation

    • Hemoglobin (Hb): a globular protein, tetramer made up of 2 alpha and 2 beta polypeptide chains

    • Each polypeptide chain contains one heme, which holds Fe2+ at its core

    • Heme: Fe2+ bound to nitrogens of porphyrin ring and histidine residue of the polypeptide chain; can form bonds with O2

    • Quaternary Hb structure: Deoxy vs Oxy Hb

      • Deoxy Hb (T-State): tense, salt bridges between alpha and beta dimers
      • Oxy Hb (R-State): relaxed, weaker interactions between heterodimers
      • Both states have a 2,3 bisphosphoglycerate (2,3 BPG) cavity

    • RBC concentration equals Hb concentration

    • Myoglobin: oxygen storage protein in the cytosol of skeletal, cardiac, and smooth muscle cells

      • Binds oxygen released by hemoglobin in tissue capillaries and diffused to tissue
      • Stored oxygen is available to mitochondria

    • Hemoglobin Oxygen Dissociation Curve: Oxygen saturation vs PO2, sigmoid curve, displays how effectively Hb releases O2 in tissues

      • Increase in affinity: multiple oxygen molecules bind to different polypeptide chains
      • Allosteric effectors: shift oxygen binding curve right or left

    • Carbon Monoxide (CO): greater affinity for Hb than O2, binds to the iron of heme

      • Smokers have higher levels of Carboxyhemoglobin (COHb)
      • CO binding changes Hb conformation from deoxy to oxy

    • Conditions: Hb saturation varies with PO2

      • Hb is 50% saturated when PO2 is 26 mmHg
      • Hb is 95% saturated when PO2 is 100 mmHg
      • Hb is 75% saturated in resting muscle capillaries when PO2 is 45 mmHg

    • Fetal Hemoglobin (HbF): higher affinity for O2, allows for exchange between mother and fetus, binds to 2,3 BPG less efficiently

      • After birth, gamma gene is turned off, and beta gene is turned on
      • Most Hb is HbA1 (adult form) after 6 months

    • Hemoglobinopathies: genetic disorders affecting Hb

      • Sickle cell: structurally abnormal Hb, HbS
      • Sickle cell disease: homozygous, two copies of mutant beta gene
      • Sickle cell trait: heterozygous, one copy of mutant beta gene
      • Thalassemias: insufficient amount of Hb due to imbalance in globin chain synthesis
      • Anemia: caused by abnormal or non-functioning globin genes
      • Ferric Heme: methemoglobin (HbM) causes cyanosis and hypoxia
      • Abnormal globin synthesis: thalassemia causes anemia

    • Cytochrome P450: liver detoxification and excretion of drugs/foreign substances

      • Some drugs induce enzymes of hepatic-metabolizing systems containing P450 heme
      • Pyrophin’s and Nucleotide Metabolism: RBCs are turned over after 4 months
      • First step: Heme degradation to bilirubin within macrophages of the reticuloendothelial system
      • Second step: Conjugated bilirubin transported to the liver, bile ducts, and excreted
      • Third step: Intestines convert some conjugated bilirubin to urobilinogen, excreted through urine
      • Fourth step: Kidneys convert some urobilinogen to urobilin, excreted through urine
      • Hyperbilirubinemia: normal serum bilirubin is less than 0.8 mg/dl, most is unconjugated
      • In hyperbilirubinemia, the level is greater than 2 mg/dl.

    • Hepatic and Erythropoietic Porphyria Cutanea Tarda: occurs on sun-exposed hands, characterized by photosensitivity due to complement/mast cell activation

    • Hemoglobin (Hb): a globular protein, tetramer made up of 2 alpha and 2 beta polypeptide chains

    • Each polypeptide chain contains one heme, which holds Fe2+ at its core

    • Heme: Fe2+ bound to nitrogens of porphyrin ring and histidine residue of the polypeptide chain; can form bonds with O2

    • Quaternary Hb structure: Deoxy vs Oxy Hb

      • Deoxy Hb (T-State): tense, salt bridges between alpha and beta dimers
      • Oxy Hb (R-State): relaxed, weaker interactions between heterodimers
      • Both states have a 2,3 bisphosphoglycerate (2,3 BPG) cavity

    • RBC concentration equals Hb concentration

    • Myoglobin: oxygen storage protein in the cytosol of skeletal, cardiac, and smooth muscle cells

      • Binds oxygen released by hemoglobin in tissue capillaries and diffused to tissue
      • Stored oxygen is available to mitochondria

    • Hemoglobin Oxygen Dissociation Curve: Oxygen saturation vs PO2, sigmoid curve, displays how effectively Hb releases O2 in tissues

      • Increase in affinity: multiple oxygen molecules bind to different polypeptide chains
      • Allosteric effectors: shift oxygen binding curve right or left

    • Carbon Monoxide (CO): greater affinity for Hb than O2, binds to the iron of heme

      • Smokers have higher levels of Carboxyhemoglobin (COHb)
      • CO binding changes Hb conformation from deoxy to oxy

    • Conditions: Hb saturation varies with PO2

      • Hb is 50% saturated when PO2 is 26 mmHg
      • Hb is 95% saturated when PO2 is 100 mmHg
      • Hb is 75% saturated in resting muscle capillaries when PO2 is 45 mmHg

    • Fetal Hemoglobin (HbF): higher affinity for O2, allows for exchange between mother and fetus, binds to 2,3 BPG less efficiently

      • After birth, gamma gene is turned off, and beta gene is turned on
      • Most Hb is HbA1 (adult form) after 6 months

    • Hemoglobinopathies: genetic disorders affecting Hb

      • Sickle cell: structurally abnormal Hb, HbS
      • Sickle cell disease: homozygous, two copies of mutant beta gene
      • Sickle cell trait: heterozygous, one copy of mutant beta gene
      • Thalassemias: insufficient amount of Hb due to imbalance in globin chain synthesis
      • Anemia: caused by abnormal or non-functioning globin genes
      • Ferric Heme: methemoglobin (HbM) causes cyanosis and hypoxia
      • Abnormal globin synthesis: thalassemia causes anemia

    • Cytochrome P450: liver detoxification and excretion of drugs/foreign substances

      • Some drugs induce enzymes of hepatic-metabolizing systems containing P450 heme
      • Pyrophin’s and Nucleotide Metabolism: RBCs are turned over after 4 months
      • First step: Heme degradation to bilirubin within macrophages of the reticuloendothelial system
      • Second step: Conjugated bilirubin transported to the liver, bile ducts, and excreted
      • Third step: Intestines convert some conjugated bilirubin to urobilinogen, excreted through urine
      • Fourth step: Kidneys convert some urobilinogen to urobilin, excreted through urine
      • Hyperbilirubinemia: normal serum bilirubin is less than 0.8 mg/dl, most is unconjugated
      • In hyperbilirubinemia, the level is greater than 2 mg/dl.

    • AMP and GMP can be converted to ATP and GTP through phosphorylation by kinases

    • IMP is a precursor for pyridine synthesis and is rapidly converted in nucleotide synthesis

    • Nucleoside monophosphate/diphosphate kinases play a role in phosphorylation of AMP to ADP and GMP to GDP

    • Adenylate Kinase and Guanylate Kinase are the kinases responsible for the phosphorylation of AMP and GMP respectively

    • Regulation of purine biosynthesis is controlled by the concentrations of both adenine and guanine nucleotides, which affects the production of IMP

    • Purine nucleotides are degraded to uric acid and excreted in the urine

    • Hypoxanthine, a base in purine nucleotides, is oxidized to uric acid by xanthine oxidase, but can be utilized by the salvage pathway

    • The salvage pathway allows the body to reuse hypoxanthine and guanine by forming IMP and GMP

    • The inability to salvage hypoxanthine and guanine due to a deficiency in HGPRT results in Lesch-Nyhan Syndrome, which is characterized by neurological abnormalities and excessive uric acid production

    • Pyrophin's and Nucleotide Metabolism can be treated with Allopurinol, an inhibitor of xanthine oxidase, and Colchicine for acute arthritic attacks in gout

    • Adenosine Deaminase is an enzyme of purine nucleotide degradation and an autosomal recessive deficiency of this enzyme results in severe combined immunodeficiency (SCID)

    • Pyrimidine synthesis regulation involves the synthesis of carbamoyl phosphate and its role in forming the orotate ring

    • UMP is decarboxylated to form uridine, which is a precursor of all pyrimidine nucleotides

    • UMP is used to form UTP through similar synthesis as purine triphosphates

    • Methylenetetrahydrofolate is involved in the formation of Thymidylate, which is essential for DNA synthesis

    • Uridine monophosphate is the precursor of all pyrimidine nucleotides

    • Deoxyribonucleotides of Adenine, Guanine, and Cytosine are synthesized from ribonucleotides by reduction of 2-hydroxyl by ribonucleotide reductase.

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    Lecture 9: Pyrophin’s and Nucleotide Metabolism PDF

    Description

    Test your knowledge of hemoglobin structure and function, as well as the characteristics of Porphyria Cutanea Tarda, a type of porphyria affecting the skin. Explore the relationship between heme, iron, and polypeptide chains in hemoglobin.

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