1. Stryer Short Course, Chapter 31
Amino Acid Synthesis
Stryer Short Course, Chapter 31

2. Nitrogen fixation
Bacteria
Nitrogenase
Costly—16 ATP per N2 molecule

3. Assimilation into Amino Acids
In microorganisms/plants: assimilation of ammonia is key—synthesis of most amino acids
Glutamine synthetase incorporates amino group
Glutamine serves as nitrogen donor for nucleic acids, etc.
Glutamine dehydrogenase: reversible reaction already observed
Glutamate can serve as nitrogen source for AA in transamination

4. Biosynthesis Dietary consideration Ambiguous
Stage of life (Arg)
Precursor (Tyr, Cys)
Mechanism of biosynthesis can be grouped

5. Amino Acid Biosynthesis* * * * * * * * * * *

6. Non-essential Amino Acid Biosynthesis
Transamination
Pyruvatealanine
Oxaloacetateaspartate
a-ketoglutarateglutamate
Amidation
Glutamine (glutamine synthetase)
Asparagine (asparagine synthetase)

7. Glutamate Backbone

8. Tyrosine
A “non-essential” amino acid
Mono-oxygenase

9. Serine 3-phosphoglycerate Serine
Serine is the building block for two amino acids that are involved in one-carbon transfer reactions
Glycine
cysteine

10. Glycine
Serineglycine
THF as a major one-carbon transfer vitamin

12. Using THF: Production of TMP
dUTP must be converted to TMP quickly
Methylene donated from THF by thymidylate synthase
THF oxidized to DHF
Chemotherapy: dUMP analog

13. Regenerating THF DHF must be reduced to THF by DHF reductase
NADPH dependent
Chemotherapy dtarget
DHF analogs such as methotrexate

14. Cysteine
Serinecysteine by incorporating sulfur from homocysteine (Made from methionine)

15. S-Adenoxylmethionine
Very active methyl carrier
Uses 3 ATP equivalents
Very reactive methyl group
Homocysteine byproduct can be used to make cysteine or regenerate methionine

16. Activated Methyl Cycle
After SAM is used, homocysteine is made back into methionine with methyl group from THF (utilizes B12)
High homocysteine levels cause oxidative damage of blood vessels—corrolates to heart disease

17. Neurotransmitters
Which amino acid is starting material for each of the following?

18. Regulation Strategies
Committed Step
Multiple isozymes
Cumulative feedback
Glutamine synthetase partially inhibited by products containing nitrogen
Feedback in branched pathways