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Radiosynthesis of 1-2-[18F]Fluoroethyl-L-Tryptophan using a One-pot, Two-step Protocol
Published on: September 21, 2021
Tryptophan oxidation in young children with environmental enteric dysfunction classified by the lactulose rhamnose
Nirupama Shivakumar1, Jean W Hsu2, Sindhu Kashyap1
1Division of Nutrition, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India.
Insights
Environmental enteric dysfunction (EED) in children does not alter tryptophan (Trp) oxidation but shows slower kynurenine (Kyn) synthesis. This suggests EED may not directly impair Trp availability for protein synthesis, contrary to previous hypotheses.
Area of Science:
- Nutritional Biochemistry
- Pediatric Gastroenterology
- Metabolic Research
Background:
- Linear growth faltering in young children is linked to environmental enteric dysfunction (EED) and altered plasma kynurenine (Kyn)/tryptophan (Trp) ratio (KTR).
- A proposed mechanism involves increased Trp catabolism due to inflammation, reducing Trp for protein synthesis and thus impairing growth.
Purpose of the Study:
- To quantify Trp oxidation rates in children with and without EED.
- To determine Trp conversion rates to Kyn in young children with and without EED.
Main Methods:
- Children aged 18-24 months from urban slums were categorized into EED (n=19) and no-EED (n=26) groups based on urinary lactulose/rhamnose ratio (LRR).
- Plasma KTR and fecal EED biomarkers were measured.
- Fed-state Trp oxidation was assessed using 13C1-Trp oral plateau feeding.
Main Results:
- No significant difference in fed-state Trp oxidation or Trp availability for protein synthesis between EED and no-EED groups.
- Significantly slower fractional synthesis rates of Kyn and reduced fraction of alanine derived from Trp in the plasma compartment for the EED group.
- Fasted KTR was higher in the EED group, but this did not correlate with altered Trp oxidation.
Conclusions:
- Static plasma KTR is an unreliable indicator of dynamic Trp flux through the oxidative pathway.
- In poor sanitary environments, children without EED exhibit faster Kyn synthesis, potentially offering cytoprotective and anti-inflammatory benefits.
- The study was registered with the Clinical Trials Registry of India (CTRI/2017/02/007921).
Background:
In young children, associations between linear growth faltering, environmental enteric dysfunction (EED), and the plasma kynurenine (Kyn)/tryptophan (Trp) ratio (KTR) have led to the proposal that higher Trp catabolism in response to intestinal/systemic inflammation limits Trp availability for protein synthesis, resulting in impaired growth.
Objectives:
We sought to estimate the Trp oxidation rate and the Trp conversion rate to Kyn in young children with and without EED.
Methods:
Children aged 18-24 mo, from urban slums, were assigned to EED (n = 19) or no-EED (n = 26) groups on the basis of a urinary lactulose/rhamnose ratio (LRR) cutoff based on mean + 2 SDs of LRR (≥0.068) in normal age- and sex-matched, high-socioeconomic status children. Plasma KTR and fecal biomarkers of EED were measured. Trp oxidation in the fed state was measured using 13C1-Trp in an oral plateau feeding protocol.
Results:
The median (quartile 1, quartile 3) fasted KTR was 0.089 (0.066, 0.110) in children with EED compared with 0.070 (0.050, 0.093) in children with no EED (P = 0.077). However, there was no difference in fed-state Trp oxidation [median (quartile 1, quartile 3) 3.1 (1.3, 5.8) compared with 3.9 (1.8, 6.0) µmol/kg FFM/h, respectively, P = 0.617] or Trp availability for protein synthesis [42.6 (36.5, 45.7) compared with 42.5 (37.9, 46.9) µmol/kg FFM/h, respectively, P = 0.868] between the groups. In contrast, the median (quartile 1, quartile 3) fractional synthesis rates of Kyn [12.5 (5.4, 20.0) compared with 21.3 (16.1, 24.7) %pool/h, P = 0.005] and the fraction of Ala derived from Trp [0.007 (0.005, 0.015) compared with 0.012 (0.008, 0.018), P = 0.037], respectively, in the plasma compartment were significantly slower in the EED group. Fecal biomarkers of EED did not differ between the groups.
Conclusions:
The static plasma KTR value is not a good indicator of the dynamic Trp flux down its oxidative pathway. In a poor sanitary environment, children without EED actually have a faster Kyn synthesis rate, which might be beneficial, because of the cytoprotective and anti-inflammatory functions of downstream metabolites. This study was registered in the Clinical Trials Registry of India as CTRI/2017/02/007921.
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