Nutrients

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15 pages, 1355 KiB

Open AccessArticle

An Increase in Liver Polyamine Concentration Contributes to the Tryptophan-Induced Acute Stimulation of Rat Hepatic Protein Synthesis

by Shinichiro Koike, Yukihito Kabuyama, Kodwo Amuzuah Obeng, Kunio Sugahara, Yusuke Sato and Fumiaki Yoshizawa

Nutrients 2020, 12(9), 2665; https://doi.org/10.3390/nu12092665 - 1 Sep 2020

Cited by 7 | Viewed by 4196

Abstract

Tryptophan has a unique role as a nutritional signaling molecule that regulates protein synthesis in mouse and rat liver. However, the mechanism underlying the stimulating actions of tryptophan on hepatic protein synthesis remains unclear. Proteomic and metabolomic analyses were performed to identify candidate [...] Read more.

Tryptophan has a unique role as a nutritional signaling molecule that regulates protein synthesis in mouse and rat liver. However, the mechanism underlying the stimulating actions of tryptophan on hepatic protein synthesis remains unclear. Proteomic and metabolomic analyses were performed to identify candidate proteins and metabolites likely to play a role in the stimulation of protein synthesis by tryptophan. Overnight-fasted rats were orally administered L-tryptophan and then sacrificed 1 or 3 h after administration. Four differentially expressed protein spots were detected in rat liver at 3 h after tryptophan administration, of which one was identified as an ornithine aminotransferase (OAT) precursor. OAT is the main catabolic enzyme for ornithine, and its expression was significantly decreased by tryptophan administration. The concentration of ornithine was increased in the liver at 3 h after tryptophan administration. Ornithine is a precursor for polyamine biosynthesis. Significantly increased concentrations of polyamines were found in the liver at 3 h after administration of tryptophan. Additionally, enhanced hepatic protein synthesis was demonstrated by oral administration of putrescine. We speculate that the increase in ornithine level through suppression of OAT expression by tryptophan administration may lead to accelerated polyamine synthesis, thereby promoting protein synthesis in the liver. Full article

(This article belongs to the Special Issue Amino Acids and Health Effects)

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10 pages, 1008 KiB

Open AccessArticle

BDK Deficiency in Cerebral Cortex Neurons Causes Neurological Abnormalities and Affects Endurance Capacity

by Anna Mizusawa, Ayako Watanabe, Minori Yamada, Rina Kamei, Yoshiharu Shimomura and Yasuyuki Kitaura

Nutrients 2020, 12(8), 2267; https://doi.org/10.3390/nu12082267 - 29 Jul 2020

Cited by 6 | Viewed by 3969

Abstract

Branched-chain amino acid (BCAA) catabolism is regulated by its rate-limiting enzyme, branched-chain α-keto acid dehydrogenase (BCKDH), which is negatively regulated by BCKDH kinase (BDK). Loss of BDK function in mice and humans leads to dysregulated BCAA catabolism accompanied by neurological symptoms such as [...] Read more.

Branched-chain amino acid (BCAA) catabolism is regulated by its rate-limiting enzyme, branched-chain α-keto acid dehydrogenase (BCKDH), which is negatively regulated by BCKDH kinase (BDK). Loss of BDK function in mice and humans leads to dysregulated BCAA catabolism accompanied by neurological symptoms such as autism; however, which tissues or cell types are responsible for the phenotype has not been determined. Since BDK is highly expressed in neurons compared to astrocytes, we hypothesized that neurons are the cell type responsible for determining the neurological features of BDK deficiency. To test this hypothesis, we generated mice in which BDK deletion is restricted to neurons of the cerebral cortex (BDK^Emx1-KO mice). Although BDK^Emx1-KO mice were born and grew up normally, they showed clasped hind limbs when held by the tail and lower brain BCAA concentrations compared to control mice. Furthermore, these mice showed a marked increase in endurance capacity after training compared to control mice. We conclude that BDK in neurons of the cerebral cortex is essential for maintaining normal neurological functions in mice, and that accelerated BCAA catabolism in that region may enhance performance in running endurance following training. Full article

(This article belongs to the Special Issue Amino Acids and Health Effects)

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10 pages, 1526 KiB

Open AccessArticle

S-Adenosylmethionine Deficiency and Brain Accumulation of S-Adenosylhomocysteine in Thioacetamide-Induced Acute Liver Failure

by Anna Maria Czarnecka, Wojciech Hilgier and Magdalena Zielińska

Nutrients 2020, 12(7), 2135; https://doi.org/10.3390/nu12072135 - 17 Jul 2020

Cited by 7 | Viewed by 4511

Abstract

Background: Acute liver failure (ALF) impairs cerebral function and induces hepatic encephalopathy (HE) due to the accumulation of neurotoxic and neuroactive substances in the brain. Cerebral oxidative stress (OS), under control of the glutathione-based defense system, contributes to the HE pathogenesis. Glutathione synthesis [...] Read more.

Background: Acute liver failure (ALF) impairs cerebral function and induces hepatic encephalopathy (HE) due to the accumulation of neurotoxic and neuroactive substances in the brain. Cerebral oxidative stress (OS), under control of the glutathione-based defense system, contributes to the HE pathogenesis. Glutathione synthesis is regulated by cysteine synthesized from homocysteine via the transsulfuration pathway present in the brain. The transsulfuration-transmethylation interdependence is controlled by a methyl group donor, S-adenosylmethionine (AdoMet) conversion to S-adenosylhomocysteine (AdoHcy), whose removal by subsequent hydrolysis to homocysteine counteract AdoHcy accumulation-induced OS and excitotoxicity. Methods: Rats received three consecutive intraperitoneal injections of thioacetamide (TAA) at 24 h intervals. We measured AdoMet and AdoHcy concentrations by HPLC-FD, glutathione (GSH/GSSG) ratio (Quantification kit). Results: AdoMet/AdoHcy ratio was reduced in the brain but not in the liver. The total glutathione level and GSH/GSSG ratio, decreased in TAA rats, were restored by AdoMet treatment. Conclusion: Data indicate that disturbance of redox homeostasis caused by AdoHcy in the TAA rat brain may represent a deleterious mechanism of brain damage in HE. The correction of the GSH/GSSG ratio following AdoMet administration indicates its therapeutic value in maintaining cellular redox potential in the cerebral cortex of ALF rats. Full article

(This article belongs to the Special Issue Amino Acids and Health Effects)

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17 pages, 1808 KiB

Open AccessArticle

Effects of L-Phenylalanine on Energy Intake and Glycaemia—Impacts on Appetite Perceptions, Gastrointestinal Hormones and Gastric Emptying in Healthy Males

by Penelope C. E. Fitzgerald, Benoit Manoliu, Benjamin Herbillon, Robert E. Steinert, Michael Horowitz and Christine Feinle-Bisset

Nutrients 2020, 12(6), 1788; https://doi.org/10.3390/nu12061788 - 16 Jun 2020

Cited by 20 | Viewed by 5976

Abstract

In humans, phenylalanine stimulates plasma cholecystokinin (CCK) and pyloric pressures, both of which are important in the regulation of energy intake and gastric emptying. Gastric emptying is a key determinant of postprandial blood glucose. We evaluated the effects of intragastric phenylalanine on appetite [...] Read more.

In humans, phenylalanine stimulates plasma cholecystokinin (CCK) and pyloric pressures, both of which are important in the regulation of energy intake and gastric emptying. Gastric emptying is a key determinant of postprandial blood glucose. We evaluated the effects of intragastric phenylalanine on appetite perceptions and subsequent energy intake, and the glycaemic response to, and gastric emptying of, a mixed-nutrient drink. The study consisted of two parts, each including 16 healthy, lean males (age: 23 ± 1 years). In each part, participants received on three separate occasions, in randomised, double-blind fashion, 5 g (Phe-5 g) or 10g (‘Phe-10 g) L-phenylalanine, or control, intragastrically, 30 min before a standardised buffet-meal (part A), or a standardised mixed-nutrient drink (part B). In part A, plasma CCK and peptide-YY (PYY), and appetite perceptions, were measured at baseline, after phenylalanine alone, and following the buffet-meal, from which energy intake was assessed. In part B, plasma glucose, glucagon-like peptide-1 (GLP-1), insulin and glucagon were measured at baseline, after phenylalanine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured by ¹³C-acetate breath-test. Phe-10 g, but not Phe-5 g, stimulated plasma CCK (p = 0.01) and suppressed energy intake (p = 0.012); energy intake was correlated with stimulation of CCK (r = −0.4, p = 0.027), and tended to be associated with stimulation of PYY (r = −0.31, p = 0.082). Both Phe-10 g and Phe-5 g stimulated insulin and glucagon (all p < 0.05), but not GLP-1. Phe-10 g, but not Phe-5 g, reduced overall plasma glucose (p = 0.043) and peak plasma glucose (p = 0.017) in response to the mixed-nutrient drink. Phenylalanine had no effect on gastric emptying of the drink. In conclusion, our observations indicate that the energy intake-suppressant effect of phenylalanine is related to the stimulation of CCK and PYY, while the glucoregulatory effect may be independent of stimulation of plasma GLP-1 or slowing of gastric emptying. Full article

(This article belongs to the Special Issue Amino Acids and Health Effects)

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11 pages, 831 KiB

Open AccessArticle

Changed Amino Acids in NAFLD and Liver Fibrosis: A Large Cross-Sectional Study without Influence of Insulin Resistance

by Takuma Hasegawa, Chikara Iino, Tetsu Endo, Kenichiro Mikami, Masayo Kimura, Naoya Sawada, Shigeyuki Nakaji and Shinsaku Fukuda

Nutrients 2020, 12(5), 1450; https://doi.org/10.3390/nu12051450 - 17 May 2020

Cited by 54 | Viewed by 5721

Abstract

Altered amino acid levels have been found in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). However, it is not clear whether this alteration is due to altered hepatic metabolism or insulin resistance. The aim of this study was to clarify the [...] Read more.

Altered amino acid levels have been found in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). However, it is not clear whether this alteration is due to altered hepatic metabolism or insulin resistance. The aim of this study was to clarify the association among amino acid levels, fatty liver, and liver fibrosis while eliminating the influence of insulin resistance. NAFLD and liver fibrosis were diagnosed using transient elastography and subjects were divided into three groups: normal, NAFLD, and liver fibrosis. To exclude the influence of insulin resistance, the subjects were matched using the homeostasis model assessment of insulin resistance (HOMA-IR). The amino acid serum levels were compared among the groups. Of 731 enrolled subjects, 251 and 33 were diagnosed with NAFLD and liver fibrosis. Although significant differences were observed among the groups in the serum levels of most amino acids, all but those of glutamate and glycine disappeared after matching for HOMA-IR. The multivariate logistic regression revealed that glutamate, glycine, and HOMA-IR were independent risk factors for liver fibrosis. The altered serum levels of most amino acids were associated with insulin resistance, while the increase in glutamate and the decrease in glycine levels were strongly associated not only with insulin resistance, but also with altered liver metabolism in patients with liver fibrosis. Full article

(This article belongs to the Special Issue Amino Acids and Health Effects)

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16 pages, 2464 KiB

Open AccessArticle

Intravenous Arginine Administration Benefits CD4⁺ T-Cell Homeostasis and Attenuates Liver Inflammation in Mice with Polymicrobial Sepsis

by Chiu-Li Yeh, Sharon Angela Tanuseputero, Jin-Ming Wu, Yi-Ru Tseng, Po-Jen Yang, Po-Chu Lee, Sung-Ling Yeh and Ming-Tsan Lin

Nutrients 2020, 12(4), 1047; https://doi.org/10.3390/nu12041047 - 10 Apr 2020

Cited by 14 | Viewed by 4594

Abstract

This study investigated the effects of a single dose of arginine (Arg) administration at the beginning of sepsis on CD4⁺ T-cell regulation and liver inflammation in C57BL/6J mice. Mice were divided into normal control (NC), sham (SH), sepsis saline (SS), and sepsis [...] Read more.

This study investigated the effects of a single dose of arginine (Arg) administration at the beginning of sepsis on CD4⁺ T-cell regulation and liver inflammation in C57BL/6J mice. Mice were divided into normal control (NC), sham (SH), sepsis saline (SS), and sepsis Arg (SA) groups. An inducible nitric oxide (NO) synthase (iNOS) inhibitor was administered to additional sepsis groups to evaluate the role of NO during sepsis. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg (300 mg/kg body weight) via tail vein 1 h after CLP. Mice were euthanized at 12 and 24 h post-CLP. Blood, para-aortic lymph nodes, and liver tissues were collected for further measurement. The findings showed that sepsis resulted in decreases in blood and para-aortic lymph node CD4⁺ T-cell percentages, whereas percentages of interleukin (IL)-4- and IL-17-expressing CD4⁺ T cells were upregulated. Compared to the SS group, Arg administration resulted in maintained circulating and para-aortic lymph node CD4⁺ T cells, an increased Th1/Th2 ratio, and a reduced Th17/Treg ratio post-CLP. In addition, levels of plasma liver injury markers and expression of inflammatory genes in liver decreased. These results suggest that a single dose of Arg administered after CLP increased Arg availability, sustained CD4⁺ T-cell populations, elicited more-balanced Th1/Th2/Th17/Treg polarization in the circulation and the para-aortic lymph nodes, and attenuated liver inflammation in sepsis. The favorable effects of Arg were abrogated when an iNOS inhibitor was administered, which indicated that NO may be participated in regulating the homeostasis of Th/Treg cells and subsequent liver inflammation during sepsis. Full article

(This article belongs to the Special Issue Amino Acids and Health Effects)

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12 pages, 916 KiB

Open AccessArticle

The Appetite−Suppressant and GLP-1-Stimulating Effects of Whey Proteins in Obese Subjects are Associated with Increased Circulating Levels of Specific Amino Acids

by Antonello E. Rigamonti, Roberto Leoncini, Alessandra De Col, Sofia Tamini, Sabrina Cicolini, Laura Abbruzzese, Silvano G. Cella and Alessandro Sartorio

Nutrients 2020, 12(3), 775; https://doi.org/10.3390/nu12030775 - 15 Mar 2020

Cited by 19 | Viewed by 10548

Abstract

The satiating effect of whey proteins depends upon their unique amino acid composition because there is no difference when comparing whey proteins or a mix of amino acids mimicking the amino acid composition of whey proteins. The specific amino acids underlying the satiating [...] Read more.

The satiating effect of whey proteins depends upon their unique amino acid composition because there is no difference when comparing whey proteins or a mix of amino acids mimicking the amino acid composition of whey proteins. The specific amino acids underlying the satiating effect of whey proteins have not been investigated to date. Aims and Methods. The aim of the present study was to evaluate the appetite-suppressant effect of an isocaloric drink containing whey proteins or maltodextrins on appetite (satiety/hunger measured by a visual analogue scale or VAS), anorexigenic gastrointestinal peptides (circulating levels of glucagon-like peptide 1 (GLP-1) and peptide tyrosine tyrosine (PYY)) and amino acids (circulating levels of single, total [TAA] and branched-chain amino acids [BCAA]) in a cohort of obese female subjects (n = 8; age: 18.4 ± 3.1 years; body mass index, BMI: 39.2 ± 4.6 kg/m²). Results. Each drink significantly increased satiety and decreased hunger, the effects being more evident with whey proteins than maltodextrins. Similarly, circulating levels of GLP-1, PYY and amino acids (TAA, BCAA and alanine, arginine, asparagine, citrulline, glutamine, hydroxyproline, isoleucine, histidine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, threonine, tyrosine, and valine) were significantly higher with whey proteins than maltodextrins. In subjects administered whey proteins (but not maltodextrins), isoleucine, leucine, lysine, methionine, phenylalanine, proline, tyrosine, and valine were significantly correlated with hunger (negatively), satiety, and GLP-1 (positively). Conclusions. Eight specific amino acids (isoleucine, leucine, lysine, methionine, phenylalanine, proline, tyrosine, and valine) were implicated in the appetite-suppressant and GLP-1-stimulating effects of whey proteins, which may be mediated by their binding with nutrient-sensing receptors expressed by L cells within the gastrointestinal wall. The long-term satiating effect of whey proteins and the effectiveness of a supplementation with these amino acids (i.e., as a nutraceutical intervention) administered during body weight reduction programs need to be further investigated. Full article

(This article belongs to the Special Issue Amino Acids and Health Effects)

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13 pages, 3282 KiB

Open AccessArticle

Glycine Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Regulating NLRP3 Inflammasome and NRF2 Signaling

by Yunchang Zhang, Xiaoshi Ma, Da Jiang, Jingqing Chen, Hai Jia, Zhenlong Wu, In Ho Kim and Ying Yang

Nutrients 2020, 12(3), 611; https://doi.org/10.3390/nu12030611 - 26 Feb 2020

Cited by 30 | Viewed by 5803

Abstract

Glycine supplementation has been reported to alleviate lipopolysaccharide (LPS)-induced lung injury in mice. However, the underlying mechanisms responsible for this beneficial effect remain unknown. In the present study, male C57BL/6 mice were treated with aerosolized glycine (1000 mg in 5 mL of 0.9% [...] Read more.

Glycine supplementation has been reported to alleviate lipopolysaccharide (LPS)-induced lung injury in mice. However, the underlying mechanisms responsible for this beneficial effect remain unknown. In the present study, male C57BL/6 mice were treated with aerosolized glycine (1000 mg in 5 mL of 0.9% saline) or vehicle (0.9% saline) once daily for 7 continuous days, and then were exposed to aerosolized LPS (5 mg in 5 mL of 0.9% saline) for 30 min to induce lung injury. Sera and lung tissues were collected 24 h post LPS challenge. Results showed that glycine pretreatment attenuated LPS-induced decreases of mucin at both protein and mRNA levels, reduced LPS-triggered upregulation of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interferons, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukins. Further study showed that glycine-reduced LPS challenge resulted in the upregulation of nuclear factor κB (NF-κB), nucleotide binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. In addition, LPS exposure led to the downregulation of NRF2 and downstream targets, which were significantly improved by glycine administration in the lung tissues. Our findings indicated that glycine pretreatment prevented LPS-induced lung injury by regulating both NLRP3 inflammasome and NRF2 signaling. Full article

(This article belongs to the Special Issue Amino Acids and Health Effects)

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20 pages, 3504 KiB

Open AccessArticle

A Special Amino-Acid Formula Tailored to Boosting Cell Respiration Prevents Mitochondrial Dysfunction and Oxidative Stress Caused by Doxorubicin in Mouse Cardiomyocytes

by Laura Tedesco, Fabio Rossi, Maurizio Ragni, Chiara Ruocco, Dario Brunetti, Michele O. Carruba, Yvan Torrente, Alessandra Valerio and Enzo Nisoli

Nutrients 2020, 12(2), 282; https://doi.org/10.3390/nu12020282 - 21 Jan 2020

Cited by 33 | Viewed by 5918

Abstract

Anthracycline anticancer drugs, such as doxorubicin (DOX), can induce cardiotoxicity supposed to be related to mitochondrial damage. We have recently demonstrated that a branched-chain amino acid (BCAA)-enriched mixture (BCAAem), supplemented with drinking water to middle-aged mice, was able to promote mitochondrial biogenesis in [...] Read more.

Anthracycline anticancer drugs, such as doxorubicin (DOX), can induce cardiotoxicity supposed to be related to mitochondrial damage. We have recently demonstrated that a branched-chain amino acid (BCAA)-enriched mixture (BCAAem), supplemented with drinking water to middle-aged mice, was able to promote mitochondrial biogenesis in cardiac and skeletal muscle. To maximally favor and increase oxidative metabolism and mitochondrial function, here we tested a new original formula, composed of essential amino acids, tricarboxylic acid cycle precursors and co-factors (named α5), in HL-1 cardiomyocytes and mice treated with DOX. We measured mitochondrial biogenesis, oxidative stress, and BCAA catabolic pathway. Moreover, the molecular relevance of endothelial nitric oxide synthase (eNOS) and mechanistic/mammalian target of rapamycin complex 1 (mTORC1) was studied in both cardiac tissue and HL-1 cardiomyocytes. Finally, the role of Krüppel-like factor 15 (KLF15), a critical transcriptional regulator of BCAA oxidation and eNOS-mTORC1 signal, was investigated. Our results demonstrate that the α5 mixture prevents the DOX-dependent mitochondrial damage and oxidative stress better than the previous BCAAem, implying a KLF15/eNOS/mTORC1 signaling axis. These results could be relevant for the prevention of cardiotoxicity in the DOX-treated patients. Full article

(This article belongs to the Special Issue Amino Acids and Health Effects)

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11 pages, 1502 KiB

Open AccessCommunication

Regulation of Skeletal Muscle Function by Amino Acids

by Yasutomi Kamei, Yukino Hatazawa, Ran Uchitomi, Ryoji Yoshimura and Shinji Miura

Nutrients 2020, 12(1), 261; https://doi.org/10.3390/nu12010261 - 19 Jan 2020

Cited by 166 | Viewed by 29599

Abstract

Amino acids are components of proteins that also exist free-form in the body; their functions can be divided into (1) nutritional, (2) sensory, and (3) biological regulatory roles. The skeletal muscle, which is the largest organ in the human body, representing ~40% of [...] Read more.

Amino acids are components of proteins that also exist free-form in the body; their functions can be divided into (1) nutritional, (2) sensory, and (3) biological regulatory roles. The skeletal muscle, which is the largest organ in the human body, representing ~40% of the total body weight, plays important roles in exercise, energy expenditure, and glucose/amino acid usage—processes that are modulated by various amino acids and their metabolites. In this review, we address the metabolism and function of amino acids in the skeletal muscle. The expression of PGC1α, a transcriptional coactivator, is increased in the skeletal muscle during exercise. PGC1α activates branched-chain amino acid (BCAA) metabolism and is used for energy in the tricarboxylic acid (TCA) cycle. Leucine, a BCAA, and its metabolite, β-hydroxy-β-methylbutyrate (HMB), both activate mammalian target of rapamycin complex 1 (mTORC1) and increase protein synthesis, but the mechanisms of activation appear to be different. The metabolite of valine (another BCAA), β-aminoisobutyric acid (BAIBA), is increased by exercise, is secreted by the skeletal muscle, and acts on other tissues, such as white adipose tissue, to increase energy expenditure. In addition, several amino acid-related molecules reportedly activate skeletal muscle function. Oral 5-aminolevulinic acid (ALA) supplementation can protect against mild hyperglycemia and help prevent type 2 diabetes. β-alanine levels are decreased in the skeletal muscles of aged mice. β-alanine supplementation increased the physical performance and improved the executive function induced by endurance exercise in middle-aged individuals. Further studies focusing on the effects of amino acids and their metabolites on skeletal muscle function will provide data essential for the production of food supplements for older adults, athletes, and individuals with metabolic diseases. Full article

(This article belongs to the Special Issue Amino Acids and Health Effects)

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Review

Jump to: Research

15 pages, 1095 KiB

Open AccessReview

Muscle Protein Synthesis and Whole-Body Protein Turnover Responses to Ingesting Essential Amino Acids, Intact Protein, and Protein-Containing Mixed Meals with Considerations for Energy Deficit

by Jess A. Gwin, David D. Church, Robert R. Wolfe, Arny A. Ferrando and Stefan M. Pasiakos

Nutrients 2020, 12(8), 2457; https://doi.org/10.3390/nu12082457 - 15 Aug 2020

Cited by 60 | Viewed by 15689

Abstract

Protein intake recommendations to optimally stimulate muscle protein synthesis (MPS) are derived from dose-response studies examining the stimulatory effects of isolated intact proteins (e.g., whey, egg) on MPS in healthy individuals during energy balance. Those recommendations may not be adequate during periods of [...] Read more.

Protein intake recommendations to optimally stimulate muscle protein synthesis (MPS) are derived from dose-response studies examining the stimulatory effects of isolated intact proteins (e.g., whey, egg) on MPS in healthy individuals during energy balance. Those recommendations may not be adequate during periods of physiological stress, specifically the catabolic stress induced by energy deficit. Providing supplemental intact protein (20–25 g whey protein, 0.25–0.3 g protein/kg per meal) during strenuous military operations that elicit severe energy deficit does not stimulate MPS-associated anabolic signaling or attenuate lean mass loss. This occurs likely because a greater proportion of the dietary amino acids consumed are targeted for energy-yielding pathways, whole-body protein synthesis, and other whole-body essential amino acid (EAA)-requiring processes than the proportion targeted for MPS. Protein feeding formats that provide sufficient energy to offset whole-body energy and protein-requiring demands during energy deficit and leverage EAA content, digestion, and absorption kinetics may optimize MPS under these conditions. Understanding the effects of protein feeding format-driven alterations in EAA availability and subsequent changes in MPS and whole-body protein turnover is required to design feeding strategies that mitigate the catabolic effects of energy deficit. In this manuscript, we review the effects, advantages, disadvantages, and knowledge gaps pertaining to supplemental free-form EAA, intact protein, and protein-containing mixed meal ingestion on MPS. We discuss the fundamental role of whole-body protein balance and highlight the importance of comprehensively assessing whole-body and muscle protein kinetics when evaluating the anabolic potential of varying protein feeding formats during energy deficit. Full article

(This article belongs to the Special Issue Amino Acids and Health Effects)

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20 pages, 1186 KiB

Open AccessReview

Amino Acids and Developmental Origins of Hypertension

by Chien-Ning Hsu and You-Lin Tain

Nutrients 2020, 12(6), 1763; https://doi.org/10.3390/nu12061763 - 12 Jun 2020

Cited by 22 | Viewed by 10975

Abstract

During pregnancy, amino acids are important biomolecules that play essential roles in fetal growth and development. Imbalanced amino acid intake during gestation may produce long-term morphological or functional changes in offspring, for example, developmental programming that increases the risk of developing hypertension in [...] Read more.

During pregnancy, amino acids are important biomolecules that play essential roles in fetal growth and development. Imbalanced amino acid intake during gestation may produce long-term morphological or functional changes in offspring, for example, developmental programming that increases the risk of developing hypertension in later life. Conversely, supplementation with specific amino acids could reverse the programming processes in early life, which may counteract the rising epidemic of hypertension. This review provides an overview of the evidence supporting the importance of amino acids during pregnancy and fetal development, the impact of amino acids on blood pressure regulation, insight from animal models in which amino acids were used to prevent hypertension of developmental origin, and interactions between amino acids and the common mechanisms underlying development programming of hypertension. A better understanding of the pathophysiological roles of specific amino acids and their interactions in developmental programming of hypertension is essential so that pregnant mothers are able to benefit from accurate amino acid supplementation during pregnancy in order to prevent hypertension development in their children. Full article

(This article belongs to the Special Issue Amino Acids and Health Effects)

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15 pages, 6441 KiB

Open AccessReview

Glutamine for Amelioration of Radiation and Chemotherapy Associated Mucositis during Cancer Therapy

by Peter M. Anderson and Rajesh V. Lalla

Nutrients 2020, 12(6), 1675; https://doi.org/10.3390/nu12061675 - 4 Jun 2020

Cited by 97 | Viewed by 18603

Abstract

Glutamine is a major dietary amino acid that is both a fuel and nitrogen donor for healing tissues damaged by chemotherapy and radiation. Evidence supports the benefit of oral (enteral) glutamine to reduce symptoms and improve and/or maintain quality of life of cancer [...] Read more.

Glutamine is a major dietary amino acid that is both a fuel and nitrogen donor for healing tissues damaged by chemotherapy and radiation. Evidence supports the benefit of oral (enteral) glutamine to reduce symptoms and improve and/or maintain quality of life of cancer patients. Benefits include not only better nutrition, but also decreased mucosal damage (mucositis, stomatitis, pharyngitis, esophagitis, and enteritis). Glutamine supplementation in a high protein diet (10 grams/day) + disaccharides, such as sucrose and/or trehalose, is a combination that increases glutamine uptake by mucosal cells. This increased topical effect can reduce painful mucosal symptoms and ulceration associated with chemotherapy and radiation in the head and neck region, esophagus, stomach and small intestine. Topical and oral glutamine seem to be the preferred routes for this amino acid to promote mucosal healing during and after cancer treatment. Full article

(This article belongs to the Special Issue Amino Acids and Health Effects)

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11 pages, 1970 KiB

Open AccessReview

Possibility of Amino Acid Treatment to Prevent the Psychiatric Disorders via Modulation of the Production of Tryptophan Metabolite Kynurenic Acid

by Tsutomu Fukuwatari

Nutrients 2020, 12(5), 1403; https://doi.org/10.3390/nu12051403 - 13 May 2020

Cited by 31 | Viewed by 5903

Abstract

Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan catabolism, acts as an antagonist for both the α7 nicotinic acetylcholine receptor and glycine coagonist sites of the N-methyl-d-aspartic acid receptor at endogenous brain concentrations. Elevation of brain kynurenic acid [...] Read more.

Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan catabolism, acts as an antagonist for both the α7 nicotinic acetylcholine receptor and glycine coagonist sites of the N-methyl-d-aspartic acid receptor at endogenous brain concentrations. Elevation of brain kynurenic acid levels reduces the release of neurotransmitters such as dopamine and glutamate, and kynurenic acid is considered to be involved in psychiatric disorders such as schizophrenia and depression. Thus, the control of kynurenine pathway, especially kynurenic acid production, in the brain is an important target for the improvement of brain function or the effective treatment of brain disorders. Astrocytes uptake kynurenine, the immediate precursor of kynurenic acid, via large neutral amino acid transporters, and metabolize kynurenine to kynurenic acid by kynurenine aminotransferases. The former transport both branched-chain and aromatic amino acids, and the latter have substrate specificity for amino acids and their metabolites. Recent studies have suggested the possibility that amino acids may suppress kynurenic acid production via the blockade of kynurenine transport or via kynurenic acid synthesis reactions. This approach may be useful in the treatment and prevention of neurological and psychiatric diseases associated with elevated kynurenic acid levels. Full article

(This article belongs to the Special Issue Amino Acids and Health Effects)

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