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Berg • Tymoczko • Stryer




     Biochemistry
               Sixth Edition




         Chapter 24:
The Biosynthesis of Amino Acids



                     Copyright © 2007 by W. H. Freeman and Company
BIOSYNTHESIS OF AMINO
             ACIDS
   All amino acids are synthesized from
    intermediates of Glycolysis, TCA or PPP.
   Different organisms vary greatly in their
    ability to synthesize the 20 amino acids.
   Amino acids are grouped by their
    metabolic precursors.
Several enzyme cofactors play important
roles in amino acid metabolism


    One carbon transfer is very important
     – Biotin
     – Tetrahydrofolate
     – S-adenosylmethionine (SAM)
Tetrahydrofolate carries
activated 1-C units at
several oxidation levels
SAM is more commonly used for CH3 transfer.
Cys is made from Ser and HomoCys
   Sulfur comes from homoCys
   The C skeleton comes from Ser
   High homocysteine levels are associated with
    vascular diseases
    • Coronary heart disease
    • Arteriosclerosis
   The molecular basis of the disease ???
    • It appears to damage cells lining blood vessels
      and to increase the growth of vascular smooth
      muscle cells
Amino acids are precursors of
    many biomolecules


   Glutathione (GSH)
   Nitric oxide (NO)
GSH serves as a buffer and antioxidant
   Protects cells from oxidative damage
   Presents at high levels (5 mM)
   It cycles between a reduced form (GSH) and an
    oxidized form (GSSG)
   GSSG is reduced to GSH by GSH reductase
   The ratio of GSH to GSSG is greater than 500 in
    most cells.
   GSH plays a key role in detoxification by reacting
    with hydrogen peroxide and organic peroxides.
   Glutathione peroxidase is remarkable in having a
    modified amino acid containing Se.
2 GSH + RO OH GSSG + H2O + ROH
Nitric oxide is formed from Arg

   NO is an important messenger
   It is made by NO synthase
   NADPH and Oxygen are required
Amino acids are converted to
       specialized products

   Porphyrins and bile pigments
    –   Biosynthesis of porphyrins
        • Formation of ALA
        • Formation of porphobilinogen

   Porphyrias
    –   Congenital erythropoietic porphyria
Other specialized products

   Creatine
   Histamine
   Serotonin
   Catecholamines
    –   Dopamine
    –   Norepinephrine
    –   Epinephrine
   Melanin
   Thyroid Hormones
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Lec14 amino synt

  • 1. Berg • Tymoczko • Stryer Biochemistry Sixth Edition Chapter 24: The Biosynthesis of Amino Acids Copyright © 2007 by W. H. Freeman and Company
  • 2. BIOSYNTHESIS OF AMINO ACIDS  All amino acids are synthesized from intermediates of Glycolysis, TCA or PPP.  Different organisms vary greatly in their ability to synthesize the 20 amino acids.  Amino acids are grouped by their metabolic precursors.
  • 3.
  • 4.
  • 5.
  • 6.
  • 7.
  • 8.
  • 9.
  • 10.
  • 11.
  • 12.
  • 13.
  • 14. Several enzyme cofactors play important roles in amino acid metabolism  One carbon transfer is very important – Biotin – Tetrahydrofolate – S-adenosylmethionine (SAM)
  • 15. Tetrahydrofolate carries activated 1-C units at several oxidation levels
  • 16.
  • 17.
  • 18.
  • 19.
  • 20. SAM is more commonly used for CH3 transfer.
  • 21.
  • 22.
  • 23.
  • 24.
  • 25.
  • 26. Cys is made from Ser and HomoCys  Sulfur comes from homoCys  The C skeleton comes from Ser  High homocysteine levels are associated with vascular diseases • Coronary heart disease • Arteriosclerosis  The molecular basis of the disease ??? • It appears to damage cells lining blood vessels and to increase the growth of vascular smooth muscle cells
  • 27.
  • 28. Amino acids are precursors of many biomolecules  Glutathione (GSH)  Nitric oxide (NO)
  • 29.
  • 30. GSH serves as a buffer and antioxidant  Protects cells from oxidative damage  Presents at high levels (5 mM)  It cycles between a reduced form (GSH) and an oxidized form (GSSG)  GSSG is reduced to GSH by GSH reductase  The ratio of GSH to GSSG is greater than 500 in most cells.  GSH plays a key role in detoxification by reacting with hydrogen peroxide and organic peroxides.  Glutathione peroxidase is remarkable in having a modified amino acid containing Se.
  • 31.
  • 32.
  • 33. 2 GSH + RO OH GSSG + H2O + ROH
  • 34.
  • 35.
  • 36. Nitric oxide is formed from Arg  NO is an important messenger  It is made by NO synthase  NADPH and Oxygen are required
  • 37.
  • 38. Amino acids are converted to specialized products  Porphyrins and bile pigments – Biosynthesis of porphyrins • Formation of ALA • Formation of porphobilinogen  Porphyrias – Congenital erythropoietic porphyria
  • 39.
  • 40.
  • 41.
  • 42. Other specialized products  Creatine  Histamine  Serotonin  Catecholamines – Dopamine – Norepinephrine – Epinephrine  Melanin  Thyroid Hormones