scholarly journals Brain Signaling of Indispensable Amino Acid Deficiency

2021 ◽  
Vol 11 (1) ◽  
pp. 191
Author(s):  
Dorothy W. Gietzen
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Piriform Cortex ◽  
Gabaergic Neurons ◽  
Inhibitory Neurons ◽  
Intact Protein ◽  
Initiation Phase ◽  
Anterior Piriform Cortex ◽  
Balanced Diet ◽  
Indispensable Amino Acids

Our health requires continual protein synthesis for maintaining and repairing tissues. For protein synthesis to function, all the essential (indispensable) amino acids (IAAs) must be available in the diet, along with those AAs that the cells can synthesize (the dispensable amino acids). Here we review studies that have shown the location of the detector for IAA deficiency in the brain, specifically for recognition of IAA deficient diets (IAAD diets) in the anterior piriform cortex (APC), with subsequent responses in downstream brain areas. The APC is highly excitable, which makes is uniquely suited to serve as an alarm for reductions in IAAs. With a balanced diet, these neurons are kept from over-excitation by GABAergic inhibitory neurons. Because several transporters and receptors on the GABAergic neurons have rapid turnover times, they rely on intact protein synthesis to function. When an IAA is missing, its unique tRNA cannot be charged. This activates the enzyme General Control Nonderepressible 2 (GCN2) that is important in the initiation phase of protein synthesis. Without the inhibitory control supplied by GABAergic neurons, excitation in the circuitry is free to signal an urgent alarm. Studies in rodents have shown rapid recognition of IAA deficiency by quick rejection of the IAAD diet.

scholarly journals Brain Signaling of Indispensable Amino Acid Deficiency

2021 ◽  
Author(s):  
Dorothy Winter Gietzen
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Piriform Cortex ◽  
Gabaergic Neurons ◽  
Inhibitory Neurons ◽  
Intact Protein ◽  
Initiation Phase ◽  
Anterior Piriform Cortex ◽  
Balanced Diet ◽  
Indispensable Amino Acids

Our health requires continual protein synthesis for maintaining and repairing tissues. For protein synthesis to function, all the essential (indispensable) amino acids (IAA) that must be available in the diet, along with those AAs that the cells can synthesize, the dispensable amino acids. Here we review studies that have shown the location of the detector for IAA deficiency in the brain, specifically for recognition of IAA deficient diets (IAAD diets) in the anterior piriform cortex (APC), with subsequent responses in downstream brain areas. The APC is highly excitable, uniquely suited to serve as an alarm for reductions in IAAs. With a balanced diet, these neurons are kept from over-excitation by GABAergic inhibitory neurons. Because several transporters and receptors on the GABAergic neurons have rapid turnover times, they rely on intact protein synthesis to function. When an IAA is missing, its unique tRNA cannot be charged. This activates the enzyme General Control Nonderepressible 2 (GCN2) that is important in the initiation phase of protein synthesis. Without the inhibitory control supplied by GABAergic neurons, excitation in the circuitry is free to signal an urgent alarm. Studies in rodents have shown rapid recognition of IAA deficiency by quick rejection of the IAAD diet.

scholarly journals Calcium-Dependent Eukaryotic Initiation Factor 2α Phosphatase Restores Control to Anterior Piriform Cortex Neural Circuitry after Activation by Essential Amino Acid Deficiency

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Gietzen DW
Keyword(s):  
Protein Synthesis ◽  
Kinase Activity ◽  
Brain Area ◽  
Piriform Cortex ◽  
Brain Slices ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Calcium Dependent ◽  
Anterior Piriform Cortex ◽  
Indispensable Amino Acids

Essential (dietary-indispensable) amino acids (IAA)s are vital precursors for protein synthesis; they cannot be synthesized in metazoans but must be obtained from food to survive. In sensing a reduction of an IAA, the mammalian anterior piriform cortex (APC)Ɨ is rapidly activated. The initial behavioral response is an abrupt end to an IAA deficient meal about 20 min after meal onset. IAA depletion in the APC activates the conserved eukaryotic initiation factor 2α (eIF2α) kinase, GCN2, via uncharged tRNA. GCN2 kinase activity increases levels of phosphorylated eIF2α (P-eIF2α), which blocks global protein synthesis such that APC inhibitory elements with short half-lives cannot be replaced. This results in disinhibition of this highly sensitive brain area. Following APC activation, a reduction in P-eIF2α releases the blockade on protein synthesis to allow recovery of inhibition in the circuit and complete the homeostatic response, restoring control in the APC. A role for calcium (Ca2+) in regulating P-eIF2α was explored here using Ca2+ blockers with immunohistochemistry and electrophysiology in APC brain slices. The responses to IAA depletion in the APC were Ca2+ dependent, showing a role for Ca2+ in the system. Yet, the kinase activity of GCN2 was unaffected by intracellular Ca2+ chelation. Thus, control must be accomplished by phosphatase activity. We suggest that regulation of P-eIF2α, and neuronal stability in the APC, require the activity of a Ca2+-dependent subunit, protein phosphatase1, of the phosphatase acting on P-eIF2α. This would implicate the Ca2+/calmodlin dependent calcineurin, and the constitutive repressor of eIF2 phosphorylation (PPP1R15B/CReP) after GCN2 activation in the brain.

scholarly journals Diets Deficient in Indispensable Amino Acids Rapidly Decrease the Concentration of the Limiting Amino Acid in the Anterior Piriform Cortex of Rats

2004 ◽  
Vol 134 (9) ◽  
pp. 2365-2371 ◽  
Author(s):  
Thomas J. Koehnle ◽  
Matthew C. Russell ◽  
Andrew S. Morin ◽  
Lesa F. Erecius ◽  
Dorothy W. Gietzen
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Piriform Cortex ◽  
Anterior Piriform Cortex ◽  
Indispensable Amino Acids ◽  
Limiting Amino Acid

scholarly journals 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

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2457 ◽  
Author(s):  
Jess A. Gwin ◽  
David D. Church ◽  
Robert R. Wolfe ◽  
Arny A. Ferrando ◽  
Stefan M. Pasiakos
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Energy Deficit ◽  
Whole Body ◽  
Intact Protein ◽  
Body Protein ◽  
Protein Feeding

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.

scholarly journals Emerging Roles of Branched-Chain Amino Acid Supplementation in Human Diseases

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Nahid Tamanna ◽  
Niaz Mahmood
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
The Body ◽  
Amino Acid Supplementation ◽  
Body Protein ◽  
Branched Chain Amino Acid ◽  
Nutritional Strategy ◽  
Indispensable Amino Acids ◽  
Extrahepatic Tissues ◽  
Branched Chain

The branched-chain amino acids (BCAAs), namely, valine, leucine, and isoleucine, are indispensable amino acids required for body protein synthesis. Unlike other amino acids, the BCAAs are primarily catabolised in the extrahepatic tissues. The BCAAs play role in regulation of protein synthesis and turnover as well as maintenance of the body glutamate-glutamine level. In strenuous and traumatic conditions, the BCAAs are oxidized which limits their availability in tissues. Such condition affects the body glutamate-glutamine pool and protein synthesis mechanisms. Thus BCCA supplementation is emerging as a nutritional strategy for treating many diseases. Many studies have found that BCAA administration is able to improve the health status of the patients suffering from different diseases even though there are conditions where they do not exert any effect. There are also some reports where elevated BCAAs have been shown to be associated with the pathogenesis of diseases. In this review, we have discussed the implication of BCAA supplementation in different pathological conditions and their relevant outcomes.

scholarly journals Dispensable Amino Acids, except Glutamine and Proline, Are Ideal Nitrogen Sources for Protein Synthesis in the Presence of Adequate Indispensable Amino Acids in Adult Men

2020 ◽  
Vol 150 (9) ◽  
pp. 2398-2404
Author(s):  
Leah Cooper ◽  
Ronald O Ball ◽  
Paul B Pencharz ◽  
Ryosei Sakai ◽  
Rajavel Elango
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Repeated Measures ◽  
Healthy Men ◽  
Adult Men ◽  
Dietary Requirement ◽  
N Sources ◽  
Indispensable Amino Acids ◽  
Dispensable Amino Acids

ABSTRACT Background Nutritionally, there is a dietary requirement for indispensable amino acids (IAAs) but also a requirement for nitrogen (N) intake for the de novo synthesis of the dispensable amino acids (DAAs). It has been suggested that there might be a dietary requirement for specific DAAs. Objectives Experiment 1 tested whether 9 of the DAAs (Ala, Arg, Asn, Asp, Gln, Glu, Gly, Pro, Ser) are ideal N sources using the indicator amino acid oxidation (IAAO) technique. Experiment 2 examined whether there is a dietary requirement for Glu in adult men. Methods Seven healthy men (aged 20–24 y) participated in 11 or 2 test diet intakes, in experiment 1 and 2, respectively, in a repeated measures design. In experiment 1, a base diet consisting of the IAA provided at the RDA was compared with test intakes with the base diet plus addition of individual DAAs to meet a 50:50 ratio of IAA:DAA on an N basis. In experiment 2, the diets corresponded to the amino acid pattern present in egg protein, in which all Glu and Gln was present as Glu, or removed, with Ser used to make the diets isonitrogenous. On each study day the IAAO protocol with l-[1-13C]phenylalanine was used to measure whole-body protein synthesis. Results In experiment 1, repeated measures ANOVA with post hoc multiple comparisons showed that 7 of the 9 DAAs (Ala, Arg, Asn, Asp, Glu, Gly, Ser) decreased IAAO significantly (P < 0.05) compared with base IAA diet, the exceptions being Gln and Pro. In experiment 2, a paired t test did not find significant (P > 0.05) differences in the IAAO in response to removal and replacement of Glu intake. Conclusions The results suggest that in healthy men most DAAs are ideal N sources for protein synthesis, in the presence of adequate IAAs, and that endogenous synthesis of Glu is sufficient. Registered clinicaltrials.gov identifier: NCT02009917.

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