Phenylbutyrate-induced glutamine depletion in humans: effect on leucine metabolism
The present study was designed to determine whether sodium phenylbutyrate (ΦB) acutely induces a decrease in plasma glutamine in healthy humans, and, if so, will decrease estimates of whole body protein synthesis. In a first group of three healthy subjects, graded doses (0, 0.18, and 0.36 g ⋅ kg ⋅ d...
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| Published in: | American journal of physiology: endocrinology and metabolism Vol. 274; no. 5; p. E801 |
|---|---|
| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
01.05.1998
|
| Subjects: | |
| ISSN: | 0002-9513, 1522-1555 |
| Online Access: | Get more information |
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| Summary: | The present study was designed to determine whether sodium phenylbutyrate (ΦB) acutely induces a decrease in plasma glutamine in healthy humans, and, if so, will decrease estimates of whole body protein synthesis. In a first group of three healthy subjects, graded doses (0, 0.18, and 0.36 g ⋅ kg
⋅ day
) of ΦB were administered for 24 h before study: postabsorptive plasma glutamine concentration declined in a dose-dependent manner, achieving an ≈25% decline for a dose of 0.36 g ΦB ⋅ kg
⋅ day
. A second group of six healthy adults received 5-h infusions ofl-[1-
C]leucine andl-[1-
C]glutamine in the postabsorptive state on two separate days: 1) under baseline conditions and 2) after 24 h of oral treatment with ΦB (0.36 g ⋅ kg
⋅ day
) in a randomized order. The 24-h phenylbutyrate treatment was associated with 1) an ≈26% decline in plasma glutamine concentration from 514 ± 24 to 380 ± 15 μM (means ± SE; P < 0.01 with paired t-test) with no change in glutamine appearance rate or de novo synthesis; 2) no change in leucine appearance rate (R
), an index of protein breakdown (123 ± 7 vs. 117 ± 5 μmol ⋅ kg
⋅ h
; not significant); 3) an ≈22% rise in leucine oxidation (Ox) from 23 ± 2 to 28 ± 2 μmol ⋅ kg
⋅ h
( P < 0.01), resulting in an ≈11% decline in nonoxidative leucine disposal (NOLD = R
- Ox), an index of protein synthesis, from 100 ± 6 to 89 ± 5 μmol ⋅ kg
⋅ h
( P < 0.05). The data suggest that, in healthy adults, 1) large doses of oral phenylbutyrate can be used as a "glutamine trap" to create a model of glutamine depletion; 2) a moderate decline in plasma glutamine does not enhance rates of endogenous glutamine production; and 3) a short-term depletion of plasma glutamine decreases estimates of whole body protein synthesis. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0002-9513 1522-1555 |
| DOI: | 10.1152/ajpendo.1998.274.5.E801 |