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 importantroles in amino acid metabolism One carbon transfer is very important – Biotin – Tetrahydrofolate – S-adenosylmethionine (SAM)
Tetrahydrofolate carriesactivated 1-C units atseveral oxidation levels
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.
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