Download Amino Acid Catabolism

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
– 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
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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