Chorismate is an important precursor for aromatic amino acids Derived from PEP and erythrose 4- phosphate First branch point of pathways, one leading to tryptophan, another to phenylalanine and tyrosine

Tryptophan biosynthesis requires PRPP, glutamine and serine

Tryptophan synthase has separable activities Has an  2  2 structure These distinct subunits (  and  ) catalyze different portions of overall reaction First reaction (  subunit) generates glyceraldehyde 3-phosphate Second reaction (  subunit) involves PLP Presents another example of substrate channeling (p. 540)

Tryptophan synthase reaction

Phenylalanine and tyrosine share prephenate as a common intermediate

Animals produce tyrosine from phenylalanine Use an enzyme phenylalanine hydroxylase, which also participates in phenylalanine catabolism, lack of this enzyme causes phenylketonuria…more on that later

Lastly - Histidine biosynthesis Histidine is derived from three precursors –PRPP contributes five carbons –Purine ring of ATP contributes nitrogen and a carbon –Glutamine supplies the second nitrogen This pathway produces AICAR, a precursor in purine biosynthesis

Orchestrating the regulation of amino acid biosynthesis No surprise – Feedback inhibition For example:

However, remember it can be more complex Concerted inhibition of glutamine synthetase Also, do not observe a equal frequency of amino acids in proteins – must make proportional amounts to be efficient Pathways can be organized into hierarchical clusters

Add parallelism through Isozymes Can modulate flux Sequential feedback inhibition

Intermediary metabolism  Amino acids  more biomolecules Glycine and succinyl-CoA Are precursors for porphyrins

Glutathione, a redox buffer

Aromatic amino acids are precursors for several biologically significant compounds Lignin – abundant plant polymer derived from tyrosine and phenyl- alanine Plant growth hormone – auxin

Including neurotransmitters All require PLP decarboxylation Know the origin of compounds in fig 22-29

Another neurotransmitter, NO And finally, back to nucleotides (in the book that is)

Amino acid catabolism Account for 10-15% of human body energy production (primary pathways are glycolysis and fatty acid oxidation) The twenty catabolic cycles converge to form five products, all entering the citric acid cycle Chapter 18

Cofactors of amino acid catabolism Know importance of H4folate, be able to recognize SAM (adoMet) and know its importance

Tetrahydrofolate Intracellular carrier of methyl groups (can also can carry a methylene, or a formimino, formyl or methenyl; different oxidative states (fig 18-16) Major source of these one carbon units is serine Although versatile, most methyl group transfers are performed by adoMet

AdoMet Synthesized from ATP and methionine Displacement of triphosphates only observed in one other known reaction involved in coenzyme B 12 synthesis

Acetyl-CoA is derived from several (ten) amino acids Pyruvate can be a common intermediate

Glycine has an alternative fate In addition to being converted to serine, and then acetyl-CoA, Glycine can be oxidized to form ammonia, carbon dioxide and a methylene group, which is transferred to tetrahydrofolate Primarily an animal pathway Also can form oxalate

Acetyl CoA is also a product of other amino acid catabolism Portions of tryptophan, lysine, phenylalanine, tyrosine, leucine and isoleucine generate acetyl-CoA or Acetoacetyl CoA or both.

Disease from deficiencies in phenylalanine and tyrosine metabolism

Loss of phenylalanine hydroxylase leads to another pathway