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Whole Body Leucine and α‐Ketoisocaproate Turnover and Transamination in Chronic Obstructive Pulmonary Disease
Author(s) -
Walker Dillon,
Thaden John,
Wierzchowska Agata,
Engelen Marielle,
Deutz Nicolaas
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.904.6
Subject(s) - transamination , leucine , medicine , copd , protein turnover , endocrinology , chemistry , pulmonary disease , amino acid , biochemistry , protein biosynthesis
We have previously demonstrated an increased whole‐body leucine (LEU) turnover in patients with chronic obstructive pulmonary disease (COPD). To examine whether this relates to underlying changes in the leucine—α‐ketoisocaproate (KIC) pathway, we measured leucine turnover, the reversible transamination of leucine and α‐ketoglutarate to α‐ketoisocaproate (KIC) and glutamate, and KIC plasma concentrations. 12 normal‐weight COPD patients with moderate to severe disease (BMI: 26.9±5.4 kg/m2, FEV1: 41.7±14.4%pred.) and 14 healthy, age‐matched controls (BMI: 27.2±0.9 kg/m2) were used for this study. Whole body kinetics and interconversion of LEU and KIC were assessed by IV administration of a pulse of L‐[5,5,5‐2H3]leucine and [1–13C]KIC followed by LC/MS/MS and GC/MS/MS measurement of plasma concentrations and enrichments. Data are summarized by their means ± SEM and significance‐tested using Student's t‐test for independent samples. Leucine turnover was greater (P=0.018) for the COPD group (87.9±1.9 μmol/kg ffm/h) than for controls (65.9±7.9 μmol/kg ffm/h) whereas KIC turnover (COPD: 46.1 ± 3.1; CON: 48.9 ± 5.5 μmol/kg ffm/h) was similar (P=0.66). Leucine deamination to KIC was greater (P=0.019) with COPD (36.5±7.2 μmol/kg ffm/h) than in controls (16.3±7.2 μmol/kg ffm/h) whereas the re‐amination of KIC to leucine (COPD: 20.5±2.3, CON: 16.9±1.4 μmol/kg ffm/h) was not different (P = 0.19). Net leucine deamination was greater (P=0.02) for the COPD group (16.0±6.3 μmol/kg ffm/h) than for controls (−0.6±1.6 μmol/kg ffm/h). Concentrations of KIC were similar between groups (P = 0.47). In conclusion, stimulated leucine deamination forming KIC seems to be responsible for increased whole body turnover of leucine in COPD.