(09-1103) Prof. Aimin Liu, Georgia State University

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  • Date/Time:
    • Tuesday November 3, 2009
      2:00 pm - 3:00 pm
  • Location: MS&E 3201A
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Shirley Tomes
Chemistry & Biochemistry
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Summary Sentence: Prof. Aimin Liu, Georgia State University

Full Summary: Prof. Aimin Liu, Georgia State University Mechanistic enzymology tryptophan oxidation Inorganic/Biochemistry Joint Divisional Seminar Series

Prof. Aimin Liu, Georgia State University

Mechanistic enzymology tryptophan oxidation

Inorganic/Biochemistry Joint Divisional Seminar Series

Tryptophan is an essential amino acid for humans. The catabolic biochemistry of this amino acid has been tightly associated with neuroscience because of serotonin (5‐HT), a catabolic product of tryptophan in the brain that functions as a neurotransmitter. Tryptophan’s connection to
neuroscience has been extended by the discovery that some of the kynurenine pathway in humans that degrades > 99% of tryptophan and is of obvious fundamental importance in human metabolism. The metabolic intermediates of the kynurenine pathway participate in normal brain function as modulators of glutamatergic neurotransmission. Although the kynurenine pathway has been known for several decades, the mechanistic enzymology of the kynurenine pathway is still poorly understood. How pathway components interact with each other remains elusive, and whether regulation is feasible is an enigma. Many enzymatic steps are either not characterized at all or not satisfactorily defined. We are studying two key enzymes of the pathway: α‐amino‐β‐carboxymuconic‐ε‐semialdehyde decarboxylase (ACMSD) and tryptophan 2,3-dioxygenase (TDO). ACMSD is at the branch point between tryptophan conversion to quinolinic acid, a neurotoxin, and complete degradation to the carbon dioxide; it is therefore notable in controlling quinolinate levels in the cell. We have recently discovered a metallocofactor from this so called “cofactor‐independent” enzyme. We have demonstrated that this enzyme belongs to a hydrolytic enzyme superfamily and is the first member to catalyze a non‐hydrolytic, C‐C bond breaking reaction. A novel concept, d-metal dependent nonoxidative decarboxylation reaction, has emerged based on our work. A new ACMSD protein family has also been defined from our structural and bioinformatics study. The reaction catalyzed by TDO is the committed and rate-limiting step of the kynurenine pathway. This enzyme employs a b‐type heme Fe‐center and it inserts both oxygen atoms into L‐tryptophan to produce N-formylkynirenien. We have trapped a compound ES-type of intermediate of TDO, consisting of an authentic oxyferryl heme close to a protein based radical. A monohydroxylated product is also detected from the TDO-mediated reaction, suggesting that the dioxygenation proceeds through a stepwise oxygen insertion.

For more information contact Prof. Wendy Kelly (404-385-1154) or Prof. Jake Soper (404-894-4022).

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graduate research
  • Created By: Shirley Tomes
  • Workflow Status: Published
  • Created On: Aug 31, 2009 - 8:00pm
  • Last Updated: Oct 7, 2016 - 9:47pm