chorismate is an important precursor for aromatic amino acids derived from pep and erythrose 4-...
TRANSCRIPT
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Chorismate is an important precursor for aromatic amino acids
• Derived from PEP and erythrose 4-phosphate
• First branch point of pathways, one leading to tryptophan, another to phenylalanine and tyrosine
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Tryptophan biosynthesis
requires PRPP, glutamineand serine
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Tryptophan synthase has separable activities
• Has an 22 structure• These distinct subunits ( and ) catalyze
different portions of overall reaction• First reaction ( subunit) generates
glyceraldehyde 3-phosphate• Second reaction ( subunit) involves PLP• Presents another example of substrate
channeling (p. 540)
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Tryptophan synthase reaction
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Phenylalanine and tyrosine share prephenate as a common intermediate
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Animals produce tyrosine from phenylalanine
• Use an enzyme phenylalanine hydroxylase, which also participates in phenylalanine catabolism, lack of this enzyme causes phenylketonuria…more on that later
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Lastly - Histidine biosynthesis
• Histidine is derived from three precursors– PRPP contributes five carbons– Purine ring of ATP contributes nitrogen and a
carbon– Glutamine supplies the second nitrogen
• This pathway produces AICAR, a precursor in purine biosynthesis
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Orchestrating the regulation of amino acid biosynthesis
• No surprise – Feedback inhibition
• For example:
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However, remember it can be more complex
• Concerted inhibition of glutamine synthetase
• Also, do not observe a equal frequency of amino acids in proteins – must make proportional amounts to be efficient
• Pathways can be organized into hierarchical clusters
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• Add parallelism through
Isozymes
Can modulate flux
Sequential feedback
inhibition
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Intermediary metabolism Amino acids more biomolecules
• Glycine and succinyl-CoA
Are precursors for porphyrins
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Glutathione, a redox buffer
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Aromatic amino acids are precursors for several biologically significant compounds
• Lignin – abundant plant polymer
derived from tyrosine and phenyl-
alanine
• Plant growth hormone – auxin
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Including neurotransmitters
• All require PLP• decarboxylation
Know the origin of compounds in fig 22-29
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Another neurotransmitter, NO
• And finally, back to nucleotides (in the book that is)
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Amino acid catabolism
• Account for 10-15% of human body energy production (primary pathways are glycolysis and fatty acid oxidation)
• The twenty catabolic cycles converge to form five products, all entering the citric acid cycle
• Chapter 18
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Cofactors of amino acid catabolism
• Know importance of H4folate, be able to recognize SAM (adoMet) and know its importance
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Tetrahydrofolate
• Intracellular carrier of methyl groups (can also can carry a methylene, or a formimino, formyl or methenyl; different oxidative states (fig 18-16)
• Major source of these one carbon units is serine
• Although versatile, most methyl group transfers are performed by adoMet
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AdoMet• Synthesized from ATP and methionine
• Displacement of triphosphates only observed in one other known reaction involved in coenzyme B12 synthesis
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Acetyl-CoA is derived from several (ten) amino acids
• Pyruvate can be a common intermediate
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Glycine has an alternative fate
• In addition to being converted to serine, and then acetyl-CoA, Glycine can be oxidized to form ammonia, carbon dioxide and a methylene group, which is transferred to tetrahydrofolate
• Primarily an animal pathway
• Also can form oxalate
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Acetyl CoA is also a product of other amino acid catabolism
• Portions of tryptophan, lysine, phenylalanine, tyrosine, leucine and isoleucine generate acetyl-CoA or Acetoacetyl CoA or both.
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Disease from deficiencies in phenylalanine and tyrosine metabolism
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Loss of phenylalanine hydroxylase leads to another pathway