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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
– Pyruvatealanine
– Oxaloacetateaspartate
– ‐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
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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