amino acid synthesis - indiana university...
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Amino Acid Synthesis
Stryer Short Course, Chapter 31
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Nitrogen fixation
• Bacteria• Nitrogenase• Costly—16 ATP per N2 molecule
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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
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Biosynthesis
• Dietary consideration
• Ambiguous– Stage of life (Arg)– Precursor (Tyr, Cys)
• Mechanism of biosynthesis can be grouped
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Amino Acid Biosynthesis
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Non‐essential Amino Acid Biosynthesis• Transamination
– Pyruvatealanine– Oxaloacetateaspartate– ‐ketoglutarateglutamate
• Amidation– Glutamine (glutamine synthetase)– Asparagine (asparagine synthetase)
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Glutamate Backbone
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Tyrosine
• A “non‐essential” amino acid• Mono‐oxygenase
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Serine
• 3‐phosphoglycerate Serine• Serine is the building block for two amino acids that are involved in one‐carbon transfer reactions– Glycine– cysteine
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Glycine
• Serineglycine– THF as a major one‐carbon transfer vitamin
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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
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Regenerating THF
• DHF must be reduced to THF by DHF reductase
• NADPH dependent• Chemotherapy dtarget
– DHF analogs such as methotrexate
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Cysteine
• Serinecysteine by incorporating sulfur from homocysteine (Made from methionine)
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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
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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
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Neurotransmitters
• Which amino acid is starting material for each of the following?
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Regulation Strategies
• Committed Step• Multiple isozymes• Cumulative feedback
– Glutamine synthetasepartially inhibited by products containing nitrogen
• Feedback in branched pathways