Volume 30, Issue S1 p. 904.6-904.6
Nutrition
Free Access

Whole Body Leucine and α-Ketoisocaproate Turnover and Transamination in Chronic Obstructive Pulmonary Disease

Dillon Walker

Dillon Walker

Center for Translational Research in Aging & Longevity, Texas A&M University, College Station, TX

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John Thaden

John Thaden

Center for Translational Research in Aging & Longevity, Texas A&M University, College Station, TX

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Agata Wierzchowska

Agata Wierzchowska

Center for Translational Research in Aging & Longevity, Texas A&M University, College Station, TX

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Marielle Engelen

Marielle Engelen

Center for Translational Research in Aging & Longevity, Texas A&M University, College Station, TX

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Nicolaas Deutz

Nicolaas Deutz

Center for Translational Research in Aging & Longevity, Texas A&M University, College Station, TX

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This abstract is from the Experimental Biology 2016 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract

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.