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, glutamineand serine

Tryptophan synthase has separable activities

• Has an 22 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 B12 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