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Chronic alterations in blood pH affect fasting‐state amino acid oxidation and myofibrillar and albumin protein synthesis in healthy young men

2017· article· en· W4389022925 on OpenAlexafffundabout
Daniel R. Moore, Paul Lysecki, Leigh Breen, Nicholas A. Burd, Kenneth Smith, Philip J. Atherton, Stuart M. Phillips

Bibliographic record

VenueThe FASEB Journal · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMuscle metabolism and nutrition
Canadian institutionsMcMaster UniversityUniversity of Toronto
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsLeucineInternal medicineEndocrinologyAlbuminChemistryMetabolismProtein metabolismAmino acidBiochemistryBiologyMedicine

Abstract

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Blood pH is typically held within a narrow range in healthy individuals. However, pathological conditions (e.g. chronic kidney disease) or net acid loads associated with Western diets and/or aging can induce shifts in acid‐base homeostasis that may alter whole body and muscle protein kinetics that, over time, could lead to changes in lean body mass. Therefore, we aimed to determine the effect of chronic alterations in blood pH over physiological and pathophysiological ranges on muscle and whole body protein metabolism in vivo in humans. After 7‐d supplementation in a randomized, crossover fashion with 0.15g/kg/d of NH 4 Cl (acid, A), KHCO 3 (base, B), or KCl (control, C), 8 healthy males (22±1y; BMI: 27.8±1.9) received a primed constant [ 13 C]leucine infusion to measure whole body leucine metabolism and myofibrillar (MYO) and albumin (ALB) protein synthesis in the fasted state. Supplementation predictably altered venous blood pH (A P ≤ 0.051; range = 7.26–7.41) but had no effect ( P >0.05) on whole body leucine turnover, leucine rate of appearance, or non‐oxidative leucine disposal (estimate of protein synthesis). Although there were no differences ( P >0.05) between conditions, leucine oxidation was negatively (r = −0.57; P <0.01) whereas leucine net balance was positively (r = 0.54; P <0.01) correlated with blood pH. There was a trend ( P =0.07) towards differences in MYO between conditions. MYO was positively correlated with blood pH (r = 0.47; P <0.05). There was no effect of blood pH on mTOR Ser2448 , 4E‐BP1 Thr37/46 , or eEF2 Thr52 phosphorylation (P>0.05). S6K1 Thr389 phosporylation was lower in A compared to B and C and its phosphorylated‐state was correlated with blood pH (r = 0.52; P=0.02) and tended to relate to MYO (r = 0.44; P =0.07). Given this, metabolic acidosis may suppress MYO in part via an impairment in mRNA translation initiation. There was no difference ( P >0.05) between conditions in candidate markers of muscle protein breakdown (i.e. total ubiquitin‐conjugated proteins and 55‐kDa actin fragment). ALB was lower in A compared to B ( P <0.05) and, similar to MYO, was correlated with blood pH (r = 0.51; P =0.01). Our data demonstrate that blood pH has a modifiable effect on whole body, muscle, and albumin protein kinetics. It is possible that normalization of acid‐base balance towards an alkolytic state will help mitigate the characteristic loss of lean body mass in populations at risk of clinical and subclinical metabolic acidosis through the attenuation of oxidative amino acid losses and an enhancement of myofibrillar protein synthetic rates. Support or Funding Information Supported by the Natural Sciences and Engineering Research Council of Canada

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.012
GPT teacher head0.251
Teacher spread0.239 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2017
Admission routes3
Has abstractyes

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