Stryer Short Course, Chapter 31

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Presentation transcript:

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 * * * * * * * * * * *

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