Questions and Answers
What is required for the formation of protoporphyrin IX from coproporphyrinogen III?
What is the role of haem synthetase (ferrochelatase) in haem synthesis?
What is the effect of low O2 tension on haem synthesis in vivo?
What is the site of haem synthesis?
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Which of the following is NOT a conjugated protein formed from haem?
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What is the effect of haem on δ-ALA synthetase?
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What is the specific cytochrome involved in the metabolism of certain drugs that increase δ -ALA synthetase?
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What is the effect of certain drugs on δ -ALA synthetase?
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What is the main component of the prosthetic groups of haemoglobin and myoglobin?
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Where does the synthesis of δ-Amino Laevulinic acid (δ-ALA) occur?
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What is the condensation product of succinyl CoA and glycine in the biosynthesis of porphyrins?
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What is the role of metal ions in porphyrins?
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What is the site of synthesis of coproporphyrinogen III and coproporphyrinogen I?
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What is the prosthetic group of chlorophyll in plants?
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What is the stage of biosynthesis where protoporphyrin IX is formed?
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What is the characteristic structure of porphyrins?
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What is the coenzyme required for the enzyme δ-ALA synthetase?
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Where does the synthesis of δ-ALA occur in liver cells?
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What is the rate-limiting enzyme in the synthetic pathway?
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What is the byproduct of the reaction catalyzed by δ-ALA dehydratase?
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What is the mechanism of inhibition of δ-ALA synthetase by haem?
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What is the function of Panthothenic acid in the synthesis of δ-ALA?
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What is the result of the condensation of two molecules of δ-ALA?
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What is the enzyme responsible for the formation of uroporphyrinogen I?
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What is the result of oxidation of uroporphyrinogen-I?
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What is the role of the isomerase (uroporphyrinogen III cosynthetase) in the formation of uroporphyrinogen III?
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What is the result of decarboxylation of uroporphyrinogen I and III?
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What is the fate of coproporphyrinogen I in the body?
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What is the enzyme system that converts coproporphyrinogen III to protoporphyrinogen IX?
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What is the location of the formation of protoporphyrin IX?
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What is the structure of coproporphyrinogen III?
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What is the fate of most of the coproporphyrinogen III in normal persons?
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What is the main function of hemoglobin in the human body?
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What is the result of increased consumption of 'haem' by cytochrome P450 during metabolism of drugs?
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What is the composition of globin in hemoglobin?
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What is the function of the pocket formed by the folded peptide chain in hemoglobin?
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What type of bonds are formed between the iron of each heme group and nitrogen atoms of histidine amino acids in hemoglobin?
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What is the percentage of hemoglobin A in adult human hemoglobin?
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What is the percentage of hemoglobin A2 in adult human hemoglobin?
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What happens to the bonds between iron and histidine molecules when hemoglobin is oxygenated?
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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.
