BiochemistrySixth Edition

Chapter 24:The Biosynthesis of Amino

Acids

Copyright © 2007 by W. H. Freeman and Company

Berg • Tymoczko • Stryer

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