King Grub
2017-05-08, 08:39
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 NH4Cl (acid, A), KHCO3 (base, B), or KCl (control, C), 8 healthy males (22±1y; BMI: 27.8±1.9) received a primed constant [13C]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<C<B; 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 mTORSer2448, 4E-BP1Thr37/46, or eEF2Thr52 phosphorylation (P>0.05). S6K1Thr389 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.
Chronic alterations in blood pH affect fasting-state amino acid oxidation and myofibrillar and albumin protein synthesis in healthy young men. The FASEB Journal, April 207, vol. 31 no. 1 Supplement 1036.14.
http://www.fasebj.org/content/31/1_Supplement/1036.14.short
Chronic alterations in blood pH affect fasting-state amino acid oxidation and myofibrillar and albumin protein synthesis in healthy young men. The FASEB Journal, April 207, vol. 31 no. 1 Supplement 1036.14.
http://www.fasebj.org/content/31/1_Supplement/1036.14.short