Amino Acid Synthesis
Stryer Short Course, Chapter 31

Nitrogen fixation
• Bacteria
• Nitrogenase
• Costly—16 ATP per N
2 molecule

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

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

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

Glutamate Backbone

Tyrosine
• A “non-essential” amino acid
• Mono-oxygenase

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

Glycine
• Serine  glycine
– THF as a major one-carbon transfer vitamin

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

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

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

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

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

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

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