Dario Vitturi
University of Alabama at Birmingham, AL·Biochemistry
Tryptophan is an essential amino acid that comes from food. Most of it is broken down in the liver through the kynurenine pathway.
- Fields
Biochemistry
Pharmacology
Physiology
- Topics
tryptophan metabolism
kynurenine pathway
Kyn-CKA
- Grants
- 1 known grant, through May 2029
What they work on
- Define how tryptophan-derived electrophiles such as Kyn-CKA form, by altering individual kynurenine pathway enzymes and searching for enzymes that remove amine groups from NFK, kynurenine and OH-kynurenine.
- Identify and measure the speed of enzymes that inactivate tryptophan-derived electrophiles, through linkage to the antioxidant glutathione or through reduction, and find new breakdown routes using isotope-labeled precursors and high-resolution mass spectrometry.
- Measure how tryptophan-derived electrophiles change cellular energy metabolism, first in liver cells (hepatocytes) and then in other cell types chosen based on where the electrophiles form in the body.
- Test how dietary tryptophan intake and the gut microbiome affect electrophile levels in the body and in tissues.
- Map where azido-labeled kynurenine is converted in living tissue, using click-chemistry tagging with spatial transcriptomics, to tell whether electrophiles act on nearby or distant cells.
More about the research
Yet this pathway also matters in the brain, kidneys, heart, immune system, tumors and pregnancy. Shifts in kynurenine metabolism often predict outcomes in aging, heart disease, organ injury, cancer and transplantation, but how these shifts affect the body is poorly understood. Using mass spectrometry, the team discovered that humans and mice make a reactive molecule called Kyn-CKA (kynurenine-carboxyketoalkene). It is an electrophile, meaning it is drawn to electrons. Kyn-CKA forms permanent bonds with cysteine amino acids on proteins, changing how those proteins work. The team has published that Kyn-CKA tunes TLR/NF-κB inflammatory signaling and Keap1/Nrf2 stress-defense signaling. Two related molecules, NFK and OH-Kyn, also produce electrophiles in the body.
Why it matters
Altered tryptophan metabolism accompanies aging, cardiovascular disease, organ injury, cancer and transplant outcomes. By defining a new class of signaling molecules made from this essential nutrient, the work could provide the biochemical groundwork for new therapies in conditions where tryptophan metabolism goes wrong.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Kristofer Fritz
University of Colorado Denver/Anschutz Medical Campus, CO·Pharmacology
Characterize how chronic alcohol metabolism changes thiol redox signaling, the on-off switching of cysteine residues in proteins, in liver cells, using redox proteomics and bioinformatics.
Andrew Paek
University of Arizona, AZ·Biochemistry
Identify proteins directly oxidized by high doses of H2O2 that switch on Group 2 stress proteins (FOXO1, NF-κB, GCN2) and block Group 1 proteins (p53, NRF2, AKT), using a targeted approach in human cells.
John Mountz
University of Alabama at Birmingham, AL·Microbiology & Immunology
Determine which IL-4-induced tryptophan metabolic signals block TLR7-driven autoantibody-precursor B cells in vivo, comparing wild-type mice with mice lacking the B-cell enzymes IL4i1 and Ido1 or the metabolite sensor AhR.
The school
University of Alabama at Birmingham: 45 labs on PI Pages, $866M a year on research, 166 research doctorates a year.
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