Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0162871 (
abdominal aortic aneurysm
)
8,664
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The eosinophilia-myalgia syndrome (EMS) outbreak of 1989 that occurred in the USA and elsewhere was caused by the ingestion of l-Tryptophan (L-Trp) solely manufactured by the Japanese company Showa Denko K.K. (SD). Six compounds present in the SD L-Trp were reported to be case-associated contaminants. However, "one" of these compounds, Peak
AAA
has remained structurally uncharacterized, despite the fact that it was described as "the only statistically significant (p=0.0014) contaminant". Here, we employ on-line microcapillary-high performance liquid chromatography-electrospray ionization mass spectrometry (LC-MS), and tandem mass spectrometry (MS/MS) to determine that Peak
AAA
is in fact two structurally related isomers. Peak
AAA
1
and Peak
AAA
2
differed in LC retention times, and were determined by accurate mass-LC-MS to both have a protonated molecular ion (MH
+)
of mass 343.239Da (Da), corresponding to a molecular formula of C
21
H
30
N
2
O
2,
and possessing eight degrees of unsaturation (DoU) for the non-protonated molecule. By comparing the LC-MS and LC-MS-MS retention times and spectra with authentic synthetic standards, Peak
AAA
1
was identified as the intermolecular condensation product of L-Trp with anteiso 7-methylnonanoic acid, to afford (S)-2-amino-3-(2-((S,E)-7-methylnon-1-en-1-yl)-1H-indol-3-yl)propanoic acid. Peak
AAA
2
was determined to be a condensation product of L-Trp with
decanoic acid
, which produced (S)-2-amino-3-(2-((E)-dec-1-en-1-yl)-1H-indol-3-yl)propanoic acid.
...
PMID:Structure determination of disease associated peak AAA from l-Tryptophan implicated in the eosinophilia-myalgia syndrome. 2903 9
Low-glucose and -insulin conditions, associated with ketogenic diets, can reduce the activity of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, potentially leading to a range of positive medical and health-related effects. Here, we determined whether mTORC1 signaling is also a target for
decanoic acid
, a key component of the medium-chain triglyceride (MCT) ketogenic diet. Using a tractable model system,
Dictyostelium
, we show that
decanoic acid
can decrease mTORC1 activity, under conditions of constant glucose and in the absence of insulin, measured by phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). We determine that this effect of
decanoic acid
is dependent on a ubiquitin regulatory X domain-containing protein, mediating inhibition of a conserved
Dictyostelium
AAA
ATPase, p97, a homolog of the human transitional endoplasmic reticulum ATPase (VCP/p97) protein. We then demonstrate that
decanoic acid
decreases mTORC1 activity in the absence of insulin and under high-glucose conditions in ex vivo rat hippocampus and in tuberous sclerosis complex (TSC) patient-derived astrocytes. Our data therefore indicate that dietary
decanoic acid
may provide a new therapeutic approach to down-regulate mTORC1 signaling.
...
PMID:Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling. 3287 8
