Catabolism of Nucleic Acid

• Catabolism of Nucleic Acids

  • Most organisms can synthesize purine and pyrimidine nucleotides from low-molecular-weight precursors in amounts sufficient for their needs.
• Catabolism of Nucleic Acids

  • These so-called de novo pathways are essentially identical throughout the biological world
• Catabolism of Nucleic Acids

  • Most organisms can also synthesize nucleotides from nucleosides or bases that become available either in the diet or through enzymatic break-down of nucleic acids
• Catabolism of Nucleic Acids

  • These processes are called salvage pathways because they involve the utilization of preformed purine and pyrimidine compounds that would otherwise be lost to biodegradation.
• Nucleic Acid Catabolism

  • Adenosine monophosphate (AMP) is deaminated to inosine monophosphate (IMP), then to hypoxanthine and finally xanthine.
• Nucleic Acid Catabolism

  • Guanosine monophosphate is also deaminated to xanthine.
  • Xanthine is further oxidized to uric acid, which is excreted in the urine of humans.
  • Cytosine and thymine are degraded to uracil, which is then degraded reductively to β-aminopropionic acid, which is also excreted in the urine.
• Gout

  • Hyperuricemia (gout) a chronic elevation of blood uric acid levels.
  • Prolonged or acute elevation of blood urate leads to its precipitation, as crystals of sodium urate, in the synovial fluid of joints
• Gout

  • These precipitates cause inflammation, resulting in a painful arthritis, which, if untreated, leads ultimately to severe degeneration of the joints.
  • Gout results either from overproduction of purine nucleotides or from impaired uric acid excretion.
• Heme Catabolism

  Red blood cells are continuously manufactured in the bone marrow and their life span is relatively short – about four months.
• Heme Catabolism: Aged red blood cells are destroyed in the phagocytic cells.
• Heme Catabolism

  When red blood cells are destroyed:

  • Globin is hydrolyzed to amino acids to be reused.
  • Iron is preserved in ferritin, an iron-carrying protein, and reused.
• Heme Catabolism

  • Heme is oxidized to biliverdin and finally reduced to bilirubin.
  • Bilirubin enters the liver via the bloodstream and is then transferred to the gallbladder where it is stored in the bile and finally excreted via the small intestine and colon.
• Heme Catabolism

  • The color of feces is provided by stercobilin, an oxidation product of bilirubin.
  • The color change observed in bruises signals the redox reactions occurring in heme catabolism: black and blue are due to congealed blood, green to the biliverdin and yellow to bilirubin.
• Formation of Bile Pigments

  • Some urobilinogen (soluble) reabsorbed through intestinal mucosa back into blood.
• Formation of Bile Pigments

  • Re-excreted by liver back into gut and excreted by kidneys into urine (urobilinogen becomes urobilin).
• Formation of Bile Pigments

  • urobilinogen to stercobilin in feces
• Heme Catabolism

  • When heme catabolism is defective, bilirubin accumulates in the blood, this condition is known as jaundice, recognized due to the distinctive color of bilirubin gives a yellow cast to the skin and the whites of the eyes.
• Heme Catabolism

  • Acute or chronic liver disease, in which the glucuronate conjugating system is impaired and albumin synthesis might be defective
• Heme Catabolism

  • Bile duct obstruction (e.g., gallstone), when bilirubin diglucuronide cannot be secreted into the intestine
• Heme Catabolism

  • Rh incompatibility reactions of infants, in which erythrocytes are destroyed by the immune system faster than the heme can be catabolized; or in premature infants, when the bilirubin conjugating system is not fully developed.