Amino Acid Synthesis Stryer Short Course, Chapter 31
Amino Acid Synthesis
Stryer Short Course, Chapter 31
Nitrogen fixation
• Bacteria• Nitrogenase• Costly—16 ATP per N2 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
– Pyruvatealanine– Oxaloacetateaspartate– ‐ketoglutarateglutamate
• 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
• Serineglycine– 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: dUMPanalog
Regenerating THF
• DHF must be reduced to THF by DHF reductase
• NADPH dependent• Chemotherapy dtarget
– DHF analogs such as methotrexate
Cysteine
• Serinecysteine 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 synthetasepartially inhibited by products containing nitrogen
• Feedback in branched pathways