Nitrogen Metabolism and Porphyrins

Nitrogen Metabolism

• Nitrogen is disposed of via the urea cycle.
• The carbon skeleton is catabolized.
• Nitrogen-containing substances include:
  • Porphyrins (heme)
  • Creatine
  • Histamine
  • Serotonin
  • Catecholamines
  • Melanin

Porphyrins

• Porphyrins are cyclic compounds that bind metal ions, usually Fe²⁺ or Fe³⁺.
• Metaloporphyrins in humans are primarily heme—a prosthetic group in hemoglobin, myoglobin, cytochromes, catalase, and tryptophan pyrrolase.
• Heme is a ferrous ion coordinated in the centre of porphyrins.
• Heme is synthesized and destroyed at a rate of 6-7 grams daily.
• Porphyrin structure is composed of four pyrrole rings linked by methylene bridges.
• Different types of porphyrins (I, II, III, IV) vary in their side chains attached to the pyrrole rings.
• Different side chains lead to different porphyrins, including uroporphyrin I and uroporphyrin III

Porphyrin Biosynthesis

• The major site of heme biosynthesis is the liver, with the initial and final steps occurring in mitochondria and other reactions taking place in the cytosol.
• The formation of 8⁻aminolevulinic acid (ALA) is a critical, rate-limiting step in heme synthesis, catalyzed by ALA synthase.
• ALA synthase is inhibited by heme.
• Two molecules of ALA condense to form porphobilinogen via amino levulinic acid dehydrase.
• Subsequent reactions lead to the formation of uroporphyrinogen.
• Uroporphyrinogen III is converted to heme via a series of decarboxylation processes.

Hemoglobin

• Hemoglobin, a protein, contains heme prosthetic groups
• The diagram shows the structure of hemoglobin with hemes highlighted.

Heme Degradation

• The lifespan of red blood cells (RBCs) is 120 days.
• RBCs are taken up by the liver, spleen, and macrophages of the reticuloendothelial system (RE).
• The breakdown of heme begins with the action of heme oxygenase.
• The first step in the degradation involves the conversion of heme to biliverdin, catalyzed by heme oxygenase.
• Biliverdin is reduced to bilirubin.
• Bilirubin is transported in the blood bound to albumin.
• When bilirubin reaches the liver, it is conjugated with glucuronic acid to increase its water solubility.
• Conjugated bilirubin is secreted into bile.
• In the intestines Bilirubin diglucuronide is hydrolyzed and reduced to yield urobilinogen.
• Some urobilinogen is reabsorbed and goes to the kidneys where it is converted to either urobilin and/or stercobilin.
• Stercobilin is responsible for the brown color of feces.
• Urobilin gives urine its yellow color.

Bilirubin Uptake and Formation of Bilirubin Diglucuronide

• Bilirubin is taken up by the liver and conjugated with glucuronic acid.
• Conjugation increases the water solubility of bilirubin.
• The resulting bilirubin diglucuronide is secreted in bile

Creatine

• Creatine phosphate is a high-energy compound found in muscle.
• It can reversibly donate a phosphate group to ADP, creating ATP during intense muscle contraction.
• Creatine kinase activity in the blood is used to diagnose myocardial infarction.
• Creatine is synthesized from glycine, the guanidino group of arginine, and a methyl group.

Creatine Degradation

• Creatine and phosphocreatine spontaneously cyclize slowly to create creatinine.
• Creatinine is excreted in the urine.
• Creatinine levels in urine are proportional to creatine levels in the blood plasma.
• Creatinine levels can be used as an indicator of total body muscle mass and kidney function.

Histamine

• Histamine is a chemical messenger involved in allergic reactions, inflammation, and neurotransmission.
• Histamine is formed from the decarboxylation of histidine.
• Histamine is secreted by mast cells during allergic reactions.

Serotonin

• Serotonin is synthesized from tryptophan.
• Serotonin is produced and stored in the small intestine, platelets, and the CNS.
• It plays a role in pain, blood pressure, body temperature, and sleep regulation.

Catecholamines

• Catecholamines (dopamine, epinephrine, norepinephrine) are biologically active amines that function as neurotransmitters in the brain and CNS.
• They are associated with the "fight-or-flight" response.
• Nor-epinephrine and epinephrine are synthesized in the adrenal medulla.
• Catecholamines are degraded by enzymatic processes.

Melanin

• Melanin is a pigment found in tissues like skin, hair, and eyes.
• Melanocytes produce melanin to protect against UV light.

This quiz explores the concepts of nitrogen metabolism, focusing on the urea cycle and the role of nitrogen-containing compounds. It also delves into porphyrins, including their structure, synthesis, and significance in the human body, particularly in relation to heme and its derivatives.