Porphyrias and Haem Synthesis
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Questions and Answers

What is required for the formation of protoporphyrin IX from coproporphyrinogen III?

  • Anaerobiosis
  • Presence of molecular O2 (correct)
  • Ferrochelatase
  • Glutathione

    • What is the role of haem synthetase (ferrochelatase) in haem synthesis?

  • Conversion of porphobilinogen to uroporphyrinogen
  • Insertion of an atom of Fe++ into protoporphyrin IX (correct)
  • Decarboxylation of coproporphyrinogen
  • Oxidation of protoporphyrinogen

    • What is the effect of low O2 tension on haem synthesis in vivo?

  • It is inhibited
  • It is unpredictable
  • It remains unaffected
  • It is stimulated (correct)

    • What is the site of haem synthesis?

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

    Which of the following is NOT a conjugated protein formed from haem?

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

    What is the effect of haem on δ-ALA synthetase?

    <p>It inhibits the activity</p> Signup and view all the answers

    What is the specific cytochrome involved in the metabolism of certain drugs that increase δ -ALA synthetase?

    <p>Cytochrome P450</p> Signup and view all the answers

    What is the effect of certain drugs on δ -ALA synthetase?

    <p>It increases the activity</p> Signup and view all the answers

    What is the main component of the prosthetic groups of haemoglobin and myoglobin?

    <p>Fe-porphyrins</p> Signup and view all the answers

    Where does the synthesis of δ-Amino Laevulinic acid (δ-ALA) occur?

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

    What is the condensation product of succinyl CoA and glycine in the biosynthesis of porphyrins?

    <p>α-Amino-β-Ketoadipic acid</p> Signup and view all the answers

    What is the role of metal ions in porphyrins?

    <p>They form complexes with the nitrogen of pyrrole rings</p> Signup and view all the answers

    What is the site of synthesis of coproporphyrinogen III and coproporphyrinogen I?

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

    What is the prosthetic group of chlorophyll in plants?

    <p>Mg-porphyrin</p> Signup and view all the answers

    What is the stage of biosynthesis where protoporphyrin IX is formed?

    <p>Stage III</p> Signup and view all the answers

    What is the characteristic structure of porphyrins?

    <p>4 pyrrole rings united by methyne bridges</p> Signup and view all the answers

    What is the coenzyme required for the enzyme δ-ALA synthetase?

    <p>Pyridoxal-P (B6-P) and Mg++</p> Signup and view all the answers

    Where does the synthesis of δ-ALA occur in liver cells?

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

    What is the rate-limiting enzyme in the synthetic pathway?

    <p>δ-ALA synthetase</p> Signup and view all the answers

    What is the byproduct of the reaction catalyzed by δ-ALA dehydratase?

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

    What is the mechanism of inhibition of δ-ALA synthetase by haem?

    <p>Feedback inhibition</p> Signup and view all the answers

    What is the function of Panthothenic acid in the synthesis of δ-ALA?

    <p>As a constituent of CoA-SH</p> Signup and view all the answers

    What is the result of the condensation of two molecules of δ-ALA?

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

    What is the enzyme responsible for the formation of uroporphyrinogen I?

    <p>Uroporphyrinogen-I synthetase</p> Signup and view all the answers

    What is the result of oxidation of uroporphyrinogen-I?

    <p>Uroporphyrin I</p> Signup and view all the answers

    What is the role of the isomerase (uroporphyrinogen III cosynthetase) in the formation of uroporphyrinogen III?

    <p>It reverses one porphobilinogen residue</p> Signup and view all the answers

    What is the result of decarboxylation of uroporphyrinogen I and III?

    <p>Formation of coproporphyrinogen I and III</p> Signup and view all the answers

    What is the fate of coproporphyrinogen I in the body?

    <p>It is excreted without being utilised</p> Signup and view all the answers

    What is the enzyme system that converts coproporphyrinogen III to protoporphyrinogen IX?

    <p>Oxidative decarboxylase system</p> Signup and view all the answers

    What is the location of the formation of protoporphyrin IX?

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

    What is the structure of coproporphyrinogen III?

    <p>Tetramethyl, tetrapropionic</p> Signup and view all the answers

    What is the fate of most of the coproporphyrinogen III in normal persons?

    <p>It is converted to protoporphyrin IX</p> Signup and view all the answers

    What is the main function of hemoglobin in the human body?

    <p>To transport oxygen from the lungs to the tissues and carbon dioxide from the tissues to the lungs</p> Signup and view all the answers

    What is the result of increased consumption of 'haem' by cytochrome P450 during metabolism of drugs?

    <p>Derepression of δ-ALA synthetase with a corresponding increase in rate of haem synthesis</p> Signup and view all the answers

    What is the composition of globin in hemoglobin?

    <p>Two α-chains and two β-chains</p> Signup and view all the answers

    What is the function of the pocket formed by the folded peptide chain in hemoglobin?

    <p>To bind to heme</p> Signup and view all the answers

    What type of bonds are formed between the iron of each heme group and nitrogen atoms of histidine amino acids in hemoglobin?

    <p>Coordination bonds</p> Signup and view all the answers

    What is the percentage of hemoglobin A in adult human hemoglobin?

    <p>97%</p> Signup and view all the answers

    What is the percentage of hemoglobin A2 in adult human hemoglobin?

    <p>2%</p> Signup and view all the answers

    What happens to the bonds between iron and histidine molecules when hemoglobin is oxygenated?

    <p>They are displaced by oxygen</p> Signup and view all the answers

    Study Notes

    Porphyrins and Porphyrins

    • Porphyrins are complex structures consisting of 4 pyrrole rings united by "methyne" bridges.
    • The nitrogen of 4 pyrrole rings can form complexes with metallic ions such as Fe++ and Mg++.
    • Porphyrins form the prosthetic groups of conjugated proteins, including:
      • Haemoglobin of mammalian erythrocytes
      • Myoglobin of muscle
      • Erythrocruorins of some invertebrates
      • Cytochromes: respiratory enzymes in the electron transport chain
      • Catalase and peroxidase enzymes
      • Oxidative enzymes like tryptophan pyrrolase
      • Chlorophyll, occurring in plants, containing Mg-porphyrin as the prosthetic group

    Biosynthesis of Porphyrins

    • Porphyrins are synthesized partly in the mitochondrion and partly in the cytosol of aerobic cells.
    • The synthesis of porphyrins can be divided into three stages:
      • Stage I: Synthesis of δ-Amino Laevulinic acid (δ-ALA)
      • Stage II: Synthesis of coproporphyrinogen III and coproporphyrinogen I
      • Stage III: Synthesis of protoporphyrin IX

    Stage I: Synthesis of δ-Amino Laevulinic Acid (δ-ALA)

    • Biosynthesis begins with the condensation of "succinyl CoA" and glycine to form "α-amino-β-ketoadipic acid".
    • The reactions are catalysed by the enzyme δ-ALA synthetase, which requires pyridoxal-P (B6-P) and Mg++ as coenzymes.
    • Panthothenic acid is also required at this stage, being a constituent of CoA-SH.

    Stage II: Synthesis of Coproporphyrinogen III and Coproporphyrinogen I

    • In this stage, two molecules of δ-ALA condense to form a molecule of porphobilinogen, which is the precursor of the "pyrrole" ring.
    • The reaction is catalysed by the enzyme δ-ALA dehydratase, for which Cu++ is required as a cofactor.
    • Regulation of this stage involves "feedback" inhibition by the end product haem.
    • The synthesis of uroporphyrinogen I and III occurs in this stage, with the major series being uroporphyrinogen III.

    Stage III: Synthesis of Protoporphyrin IX

    • Coproporphyrinogen III enters the mitochondrion and is converted to protoporphyrin IX.
    • The steps between coproporphyrinogen III and protoporphyrin IX are not fully understood.
    • An oxidative decarboxylase system containing flavins as coenzyme converts coproporphyrinogen III to protoporphyrinogen IX.
    • Protoporphyrinogen IX is converted to protoporphyrin IX by another oxidase enzyme.

    Formation of Haem and Haemoproteins

    • Insertion of an atom of Fe++ into the central position of protoporphyrin IX is catalysed by haem synthetase (ferrochelatase).
    • The haem is then coupled to various proteins to form conjugated proteins, including haemoglobin, myoglobin, cytochrome C, catalases, and peroxidases.

    Regulatory Influences and Effects of Inhibitors

    • Oxygen has a complex effect on haem synthesis, stimulating it in vivo and inhibiting it in vitro.
    • Enzyme inhibition, particularly of δ-ALA synthetase, is an important site of regulation.
    • Haem, the end-product of the metabolic sequence, inhibits the activity of synthetase.
    • Certain drugs can result in a marked increase in hepatic δ-ALA synthetase, leading to increased porphyrin synthesis.

    Hemoglobin Metabolism

    • Hemoglobin is a conjugated protein found only in red blood cells, with a main function of transporting oxygen from the lungs to the tissues and carbon dioxide from the tissues to the lungs.
    • Hemoglobin consists of a specialized protein called globin, which is tightly bound to 4 heme molecules.
    • Globin is a protein with four peptide chains joined together by non-covalent bonds (tetramer).
    • There are several types of hemoglobin, including HbA, HbA2, HbF, and HbA1, which vary in the primary structure of the peptide chains of globin.
    • Hemoglobin A is the major hemoglobin in adults, comprising 97% of total hemoglobin.

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    Description

    This quiz covers the synthesis of haem and porphyrias, including their structures and functions. It's designed for students of clinical biochemistry and laboratory medicine.

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