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The Role of Large Neutral Amino Acid Transporter (LAT1) in Cancer.
Lu, X
Current cancer drug targets. 2019;(11):863-876
Abstract
BACKGROUND The solute carrier family 7 (SLC7) can be categorically divided into two subfamilies, the L-type amino acid transporters (LATs) including SLC7A5-13, and SLC7A15, and the cationic amino acid transporters (CATs) including SLC7A1-4 and SLC7A14. Members of the CAT family transport predominantly cationic amino acids by facilitating diffusion with intracellular substrates. LAT1 (also known as SLC7A5), is defined as a heteromeric amino acid transporter (HAT) interacting with the glycoprotein CD98 (SLC3A2) through a conserved disulfide to uptake not only large neutral amino acids, but also several pharmaceutical drugs to cells. METHODS In this review, we provide an overview of the interaction of the structure-function of LAT1 and its essential role in cancer, specifically, its role at the blood-brain barrier (BBB) to facilitate the transport of thyroid hormones, pharmaceuticals (e.g., I-DOPA, gabapentin), and metabolites into the brain. RESULTS LAT1 expression increases as cancers progress, leading to higher expression levels in highgrade tumors and metastases. In addition, LAT1 plays a crucial role in cancer-associated reprogrammed metabolic networks by supplying tumor cells with essential amino acids. CONCLUSION The increasing understanding of the role of LAT1 in cancer has led to an increase in interest surrounding its potential as a drug target for cancer treatment.
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2.
Novel Physiological Functions of Branched-Chain Amino Acids.
Shimomura, Y, Kitaura, Y, Kadota, Y, Ishikawa, T, Kondo, Y, Xu, M, Ota, M, Morishita, Y, Bariuan, JV, Zhen, H
Journal of nutritional science and vitaminology. 2015;:S112-4
Abstract
Branched-chain amino acids (BCAAs) are essential amino acids for humans and are major building blocks of proteins. Recent studies indicate that BCAAs act not only as components of proteins, but also as nutrasignals. In this review, we summarize the findings of recent studies investigating the physiological functions of BCAAs in the regulation of protein and glucose metabolism and brain function.
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3.
Nutritional interventions in sarcopenia: a critical review.
Hickson, M
The Proceedings of the Nutrition Society. 2015;(4):378-86
Abstract
The aim of the present paper is to critically review the details of the published nutrition intervention trials, with and without exercise, targeting sarcopenia. Sarcopenia is the loss of muscle mass, strength and/or performance with age. Since amino acids and energy are required for muscle synthesis it is possible that nutritional intake influences sarcopenia. Nutritional studies are challenging to carry out because of the complexity of modulating dietary intake. It is very difficult to change one nutrient without influencing many others, which means that many of the published studies are problematic to interpret. The studies included evaluate whole protein, essential amino acids and β-hydroxyl β-methylbutyrate (HMB). Whole-protein supplementation failed to show a consistent effect on muscle mass, strength or function. This can be explained by the variations in study design, composition of the protein supplement and the failure to monitor voluntary food intake, adherence and baseline nutritional status. Essential amino-acid supplements showed an inconsistent effect but there are only two trials that have significant differences in methodology and the supplement used. The HMB studies are suggestive of a beneficial effect on older adults, but larger well-controlled studies are required that measure outcomes relevant to sarcopenia, ideally in sarcopenic populations. The issues of timing and distribution of protein intake, and increased splanchnic amino-acid sequestration are discussed, and recommendations for future trials are made.
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4.
Plastidic aspartate aminotransferases and the biosynthesis of essential amino acids in plants.
de la Torre, F, Cañas, RA, Pascual, MB, Avila, C, Cánovas, FM
Journal of experimental botany. 2014;(19):5527-34
Abstract
In the chloroplasts and in non-green plastids of plants, aspartate is the precursor for the biosynthesis of different amino acids and derived metabolites that play distinct and important roles in plant growth, reproduction, development or defence. Aspartate biosynthesis is mediated by the enzyme aspartate aminotransferase (EC 2.6.1.1), which catalyses the reversible transamination between glutamate and oxaloacetate to generate aspartate and 2-oxoglutarate. Plastids contain two aspartate aminotransferases: a eukaryotic-type and a prokaryotic-type bifunctional enzyme displaying aspartate and prephenate aminotransferase activities. A general overview of the biochemistry, regulation, functional significance, and phylogenetic origin of both enzymes is presented. The roles of these plastidic aminotransferases in the biosynthesis of essential amino acids are discussed.
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5.
Do ketoanalogues still have a role in delaying dialysis initiation in CKD predialysis patients?
Aparicio, M, Bellizzi, V, Chauveau, P, Cupisti, A, Ecder, T, Fouque, D, Garneata, L, Lin, S, Mitch, W, Teplan, V, et al
Seminars in dialysis. 2013;(6):714-9
Abstract
Early versus later start of dialysis is still a matter of debate. Low-protein diets have been used for many decades to delay dialysis initiation. Protein-restricted diets (0.3-0.6 g protein/kg/day) supplemented with essential amino acids and ketoanalogues (sVLPD) can be offered, in association with pharmacological treatment, to motivated stage 4-5 chronic kidney disease (CKD) patients not having severe comorbid conditions; they probably represent 30-40% of the concerned population. A satisfactory adherence to such dietary prescription is observed in approximately 50% of the patients. While the results of the studies on the effects of this diet on the rate of progression of renal failure remain inconclusive, they are highly significant when initiation of dialysis is the primary outcome. The correction of uremic symptoms allows for initiation of dialysis treatment at a level of residual renal function lower than that usually recommended. Most of the CKD-associated complications of cardiovascular and metabolic origin, which hamper both lifespan and quality of life, are positively influenced by the diet. Lastly, with regular monitoring jointly assumed by physicians and dietitians, nutritional status is well preserved as confirmed by a very low mortality rate and by the absence of detrimental effect on the long-term outcome of patients once renal replacement therapy is initiated. On account of its feasibility, efficacy and safety, sVLPD deserves a place in the management of selected patients to safely delay the time needed for dialysis.
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6.
Methods to assess amino acid requirements in humans.
Kurpad, AV, Thomas, T
Current opinion in clinical nutrition and metabolic care. 2011;(5):434-9
Abstract
PURPOSE OF REVIEW There are now different stable isotopic methods to measure minimum daily human indispensable amino acid (IAA) requirements. There has been debate on the appropriateness of statistical methods used to define the nature of change in the response. RECENT FINDINGS Current isotopic methods measure daily amino acid oxidation and balance of the IAA under test, or of a selected indicator amino acid, to graded intakes of the test IAA. A key concern is how response curves of oxidation/balance are analyzed to find the inflection point (breakpoint) at which the intake requirement is identified. Evaluating the pattern of the response to identify a breakpoint by a two-phase regression appears best. The indicator amino acid oxidation method has also been shortened and developed into a noninvasive protocol suitable for different populations and age groups. SUMMARY The indicator amino acid oxidation and balance method might be considered the best approach currently available, but it is challenging. The short-term indicator oxidation method is noninvasive and nondemanding. IAA requirements, based on these methods, have implications for the quality of protein in the dietary intake of populations. Methods that assess the IAA requirements to support optimal body function also need to be developed.
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Essential amino acid sensing, signaling, and transport in the regulation of human muscle protein metabolism.
Dickinson, JM, Rasmussen, BB
Current opinion in clinical nutrition and metabolic care. 2011;(1):83-8
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Abstract
PURPOSE OF REVIEW To highlight the recent research pertaining to the cellular mechanisms linking amino acid availability, mTORC1 signaling, and muscle protein metabolism. RECENT FINDINGS Activation of the mTORC1 pathway in response to amino acids may be dependent upon cellular relocalization of mTORC1, a process that appears to involve the Rag GTPases. Recent studies have also identified other intracellular proteins, such as hVps34 and MAP4K3, and specific amino acid transporters as necessary links between amino acid availability and mTORC1. In human skeletal muscle, it appears that mTORC1 activity increases the expression of several amino acid transporters, which may be an important adaptive response to sensitize muscle to a subsequent increase in amino acid availability. SUMMARY The precise cellular mechanisms linking amino acids to mTORC1 signaling and muscle protein metabolism are currently not well understood. More defined cellular mechanisms are beginning to emerge suggesting a role for several intracellular proteins including hVps34, MAP4K3, and Rag GTPases. Additionally, specific amino acid transporters may have a role both upstream and downstream of mTORC1. Continued investigation into the precise cellular mechanisms linking amino acid availability and muscle protein metabolism will help facilitate improvements in existing therapies for conditions of muscle wasting.
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Potential application of essential amino Acid supplementation to treat sarcopenia in elderly people.
Henderson, GC, Irving, BA, Nair, KS
The Journal of clinical endocrinology and metabolism. 2009;(5):1524-6
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Calories and cachexia.
Morley, JE
Current opinion in clinical nutrition and metabolic care. 2009;(6):607-10
Abstract
PURPOSE OF REVIEW Anorexia and weight loss are associated with increased mortality in cachectic patients. The role of caloric supplementation is controversial. The purpose of this review is to examine the role of calorie supplementation in cachexia. RECENT FINDINGS Caloric supplementation improves outcomes in malnourished hospital patients and malnourished older persons. It may improve the quality of life in cancer patients and for those persons receiving palliative care. Caloric supplementation should include a balanced essential amino acid supplement given at least twice a day. The role of eicosapentanoic acid as a supplement is controversial. All caloric supplements should be given between and not with meals. SUMMARY Caloric supplementation rich in protein and with adequate vitamin D should be given between meals to all patients with cachexia.
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[The significance of perioperative immunonutrition].
Schreiter, D, Rabald, S, Bercker, S, Kaisers, UX
Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie : AINS. 2008;(7-8):540-5; quiz 546
Abstract
Perioperative immunonutrition is aiming at modulating altered immunological and metabolic functions in the context of major surgery. It is defined as the supplementation of constitutionally essential substrates such as glutamine, arginine, omega-3-fatty acids or nucleotides. The application of such formula is recommended for patients undergoing major abdominal-surgical procedures and tumour surgery in the head neck area. The substitution should be given 5-7 days before and after the intervention.