Nitrogen Metabolism and Porphyrins Overview
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Questions and Answers

What is the primary physiological role of serotonin?

  • Hormone production
  • Pain regulation (correct)
  • Cell division
  • Muscle contraction
  • What is the rate limiting step in the biosynthesis of catecholamines?

  • DOPA degradation
  • Tyrosine hydroxylation (correct)
  • Epinephrine synthesis
  • Norepinephrine storage
  • What triggers the release of epinephrine and norepinephrine?

  • High cholesterol levels
  • Relaxation and sleep
  • Fright, exercise, and low glucose levels (correct)
  • Sustained fasting
  • Which enzyme is responsible for the oxidative deamination of catecholamines?

    <p>Monoamine oxidase (MAO)</p> Signup and view all the answers

    What substance results from the decarboxylation of histidine?

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

    What is the primary function of porphyrins in the human body?

    <p>To bind metal ions and function as prosthetic groups.</p> Signup and view all the answers

    Which substance is a precursor for the biosynthesis of porphyrins?

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

    What inhibits the enzyme ALA synthase in the biosynthesis of porphyrins?

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

    Where in the body is the major site of heme biosynthesis?

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

    What is the product formed when uroporphyrinogen III undergoes decarboxylation?

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

    What is formed during the initial step of heme degradation?

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

    How long is the typical lifespan of a red blood cell (RBC)?

    <p>120 days</p> Signup and view all the answers

    What is the role of ALA dehydrase in porphyrin biosynthesis?

    <p>Catalyzes the condensation of two ALA molecules.</p> Signup and view all the answers

    What is the primary function of Bilirubin glucuronyl transferase in the liver?

    <p>To increase the solubility of Bilirubin</p> Signup and view all the answers

    Which condition is NOT a type of jaundice mentioned?

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

    Which compound is primarily responsible for regenerating ATP during intense muscular contraction?

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

    What is a significant consequence of high bilirubin levels in the body?

    <p>Toxicity to the central nervous system</p> Signup and view all the answers

    Which component is involved in the synthesis of creatine?

    <p>Glycine and the guanidino group of arginine</p> Signup and view all the answers

    What is one primary role of histamine in the body?

    <p>Mediating allergic and inflammatory responses</p> Signup and view all the answers

    What does the presence of creatine kinase in plasma indicate?

    <p>Myocardial infarction diagnosis</p> Signup and view all the answers

    What color is associated with stercobillin, a product of bilirubin degradation?

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

    Study Notes

    Nitrogen Metabolism

    • Nitrogen disposal via the urea cycle
    • Catabolism of carbon skeletons
    • Breakdown of nitrogen-containing substances:
      • Porphyrins (e.g., heme)
      • Creatine
      • Histamine
      • Serotonin
      • Catecholamines
      • Melanin

    Porphyrins

    • Porphyrins are cyclic compounds binding metal ions (usually Fe²⁺ or Fe³⁺)
    • Metaloporphyrins in humans are primarily heme
    • Heme is a prosthetic group for hemoglobin, myoglobin, cytochromes, catalase, and tryptophan pyrrolase
    • Heme synthesis and breakdown occur at a rate of 6-7 grams per day
    • Porphyrin structure: ring structure of four pyrrole rings linked by methylene bridges
    • Side chains: different porphyrin types (I, II, III, IV) are distinguished by the side chains attached to the pyrrole rings
    • Porphyrins contain side chains on each of the four pyrrole rings:
      • In type I porphyrins, side chains (acetate) alternate with propionate.
      • Type III porphyrins are important in humans.

    Porphyrin Biosynthesis

    • The major site of heme synthesis is the liver
    • The first reaction and last three reactions occur in mitochondria
    • Other reactions occur in the cytosol
    • Formation of 8-amino levulinic acid (ALA):
      • ALA synthesis is the rate-limiting step.
    • ALA is formed from glycine and succinyl CoA
    • ALA synthase catalyzes this reaction
    • ALA synthase is inhibited by heme

    Porphyrin Biosynthesis (Cont.)

    • Formation of porphobilinogen:
      • Two molecules of ALA condense to form porphobilinogen
    • Formation of uroporphyrinogen:
      • Four molecules of porphobilinogen condense to form uroporphyrinogen III

    Formation of Heme

    • Uroporphyrinogen III is converted to heme by a series of decarboxylation processes.

    Degradation of Heme

    • Red blood cell (RBC) lifespan is 120 days
    • RBCs are taken up by the liver, spleen, and macrophages and degraded by the reticulo-endothelial system (RE)
    • Heme Degradation process involves heme oxygenase, biliverdin, and bilirubin.

    Bilirubin Formation

    • The first step in heme degradation is catalyzed by the microsomal heme oxygenase enzyme in the ER cells.
    • The enzyme adds a hydroxyl group (-OH) to the methylene bridge, causing oxidation to carbon monoxide (CO) and releasing iron (Fe³⁺)
    • The product of this reaction is biliverdin, which is reduced to bilirubin.

    Bilirubin Uptake by the Liver

    • Bilirubin is taken up by liver hepatocytes.

    Formation of Bilirubin Diglucuronide

    • In hepatocytes, the solubility of bilirubin increases by adding two molecules of glucuronic acid catalyzed by bilirubin UDP-glucuronyl transferase using UDP-glucuronic acid.

    Excretion of Bilirubin into Bile

    • Bilirubin diglucuronide is transported into bile.
    • Formation of urobilins in the intestine: Bilirubin glucuronide is hydrolyzed and reduced to urobilinogen. Part of it is then reabsorbed by the gut and converted to urobilin in the kidneys.

    Jaundice

    • High levels of bilirubin in the body can lead to jaundice, which is the yellowing of skin and sclera.
    • Different types of jaundice exist including hemolytic, obstructive, and hepatocellular jaundice. This condition can be caused by sickle cell anemia, malaria, bile duct obstruction, or liver damage.
    • Jaundice in newborns due to a decrease in the activity of bilirubin glucuronyl transferase.

    Creatine

    • Creatine phosphate is a high-energy compound formed in muscle tissue.
    • Creatine phosphate donates a phosphate group to ADP to produce ATP.
    • This is crucial for rapid ATP production during intense muscle contraction.
    • Creatine kinase is present in plasma and can be used as a diagnostic tool for conditions like myocardial infarction

    Creatine Synthesis

    • Synthesis occurs from glycine, the guanidino group of arginine, and a methyl group from activated methionine.

    Creatine Degradation

    • Creatine and phosphocreatine spontaneously cyclize to form creatinine that's excreted in urine.
    • Urine creatinine levels are indicative of total body mass and kidney function.

    Histamine

    • Histamine is a chemical messenger involved in a variety of cellular responses, including allergic reactions, inflammation, gastric acid secretion and neurotransmission in the brain.
    • Histamine is formed from the decarboxylation of histidine.
    • Released from mast cells in response to allergic reactions

    Serotonin

    • Serotonin is synthesized from tryptophan.
    • Serotonin is stored in the small intestine, platelets, and the central nervous system (CNS).
    • Serotonin plays many roles in the body, including regulating functions like pain, blood pressure, temperature, and sleep.

    Catecholamines

    • Dopamine, epinephrine, and norepinephrine are biologically active amines
    • These catecholamines function as neurotransmitters in the brain and central nervous system (CNS) they are part of the sympathetic nervous system's "fight or flight" response
    • Catecholamines are synthesized in the adrenal medulla.

    Catecholamine Synthesis

    • Tyrosine is the starting point for catecholamine synthesis. 
    • Tyrosine is converted to L-DOPA (dihydroxyphenylalanine), which is then converted to dopamine and further to norepinephrine, epinephrine.

    Melanin

    • Melanin is a pigment found in various tissues, protecting them from harmful UV effects from sunlight(such as eye, skin, and hair).
    • Melanocytes are skin cells that are responsible for the synthesis and distribution of melanin.
    • Tyrosine is involved in melanin production.

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    Description

    Explore key concepts in nitrogen metabolism, focusing on the urea cycle and the breakdown of nitrogen-containing substances. Delve into the structure and function of porphyrins, including their role in heme synthesis and the different types based on side chains.

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