Whole Body Leucine and -Ketoisocaproate Turnover and Transamination in Chronic Obstructive Pulmonary Disease
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abstract
We have previously demonstrated an increased wholebody leucine (LEU) turnover in patients with chronic obstructive pulmonary disease (COPD). To examine whether this relates to underlying changes in the leucineketoisocaproate (KIC) pathway, we measured leucine turnover, the reversible transamination of leucine and ketoglutarate to ketoisocaproate (KIC) and glutamate, and KIC plasma concentrations. 12 normalweight COPD patients with moderate to severe disease (BMI: 26.95.4 kg/m2, FEV1: 41.714.4%pred.) and 14 healthy, agematched controls (BMI: 27.20.9 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[5,5,52H3]leucine and [113C]KIC followed by LC/MS/MS and GC/MS/MS measurement of plasma concentrations and enrichments. Data are summarized by their means SEM and significancetested using Student's ttest for independent samples. Leucine turnover was greater (P=0.018) for the COPD group (87.91.9 mol/kg ffm/h) than for controls (65.97.9 mol/kg ffm/h) whereas KIC turnover (COPD: 46.1 3.1; CON: 48.9 5.5 mol/kg ffm/h) was similar (P=0.66). Leucine deamination to KIC was greater (P=0.019) with COPD (36.57.2 mol/kg ffm/h) than in controls (16.37.2 mol/kg ffm/h) whereas the reamination of KIC to leucine (COPD: 20.52.3, CON: 16.91.4 mol/kg ffm/h) was not different (P = 0.19). Net leucine deamination was greater (P=0.02) for the COPD group (16.06.3 mol/kg ffm/h) than for controls (0.61.6 mol/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.
