-
1.
Amino Acid Metabolism in Cancer Drug Resistance.
Yoo, HC, Han, JM
Cells. 2022;(1)
Abstract
Despite the numerous investigations on resistance mechanisms, drug resistance in cancer therapies still limits favorable outcomes in cancer patients. The complexities of the inherent characteristics of tumors, such as tumor heterogeneity and the complicated interaction within the tumor microenvironment, still hinder efforts to overcome drug resistance in cancer cells, requiring innovative approaches. In this review, we describe recent studies offering evidence for the essential roles of amino acid metabolism in driving drug resistance in cancer cells. Amino acids support cancer cells in counteracting therapies by maintaining redox homeostasis, sustaining biosynthetic processes, regulating epigenetic modification, and providing metabolic intermediates for energy generation. In addition, amino acid metabolism impacts anticancer immune responses, creating an immunosuppressive or immunoeffective microenvironment. A comprehensive understanding of amino acid metabolism as it relates to therapeutic resistance mechanisms will improve anticancer therapeutic strategies.
-
2.
Fueling T-cell Antitumor Immunity: Amino Acid Metabolism Revisited.
Han, C, Ge, M, Ho, PC, Zhang, L
Cancer immunology research. 2021;(12):1373-1382
Abstract
T cells are the key players in eliminating malignant tumors. Adoptive transfer of tumor antigen-specific T cells and immune checkpoint blockade has yielded durable antitumor responses in the clinic, but not all patients respond initially and some that do respond eventually have tumor progression. Thus, new approaches to enhance the utility of immunotherapy are needed. T-cell activation and differentiation status are tightly controlled at the transcriptional, epigenetic, and metabolic levels. Amino acids are involved in multiple steps of T-cell antitumor immunity, including T-cell activation, proliferation, effector function, memory formation as well as functional exhaustion. In this review, we briefly discuss how amino acid metabolism is linked to T-cell fate decisions and summarize how amino acid deprivation or accumulation of certain amino acid metabolites within the tumor microenvironment diminishes T-cell functionality. Furthermore, we discuss potential strategies for immunotherapy via modulating amino acid metabolism either in T cells intrinsically or extrinsically to achieve therapeutic efficacy.
-
3.
The significant role of amino acids during pregnancy: nutritional support.
Manta-Vogli, PD, Schulpis, KH, Dotsikas, Y, Loukas, YL
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2020;(2):334-340
Abstract
Background: Pregnancy is characterized by a complexity of metabolic processes that may impact fetal development and infant health outcome. Normal fetal growth and development depend on a continuous supply of nutrients via the placenta. The placenta transports, utilizes, produces, and interconverts amino acids (AAs).Findings: Concentrations of both nonessential and essential AAs in maternal plasma decrease in early pregnancy and persist at low concentrations throughout. The decline is greatest for the glucogenic AAs and AAs of the urea cycle. Additionally, there is a large placental utilization of the branched-chain AAs, some of which are transaminated to alpha ketoacids and contribute to placental ammonia production. Both nonessential and essential AAs regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of organisms. Some of the nonessential AAs (e.g. glutamine, glutamate, and arginine) play also important roles in regulating gene expression, cell signaling, antioxidant responses, immunity, and neurological function.Conclusions: Nutritional support during pregnancy is of great interest focusing not only to common pregnancies but also to those with low socioeconomic status, vegan-vegetarian groups, and pregnant women with metabolic disorders, the most known maternal phenylketonuria. The latter is of great interest because phenylalanine must be within the recommended range throughout pregnancy in addition to other nutrients such as vitamin B12, folate, etc. Loss of the adherence to this specific diet results in congenital malformations of the fetus. In addition to the routine laboratory test, quantitation of plasma AAs may be necessary throughout pregnancy.
-
4.
Free Amino Acids in Human Milk: A Potential Role for Glutamine and Glutamate in the Protection Against Neonatal Allergies and Infections.
van Sadelhoff, JHJ, Wiertsema, SP, Garssen, J, Hogenkamp, A
Frontiers in immunology. 2020;:1007
Abstract
Breastfeeding is indicated to support neonatal immune development and to protect against neonatal infections and allergies. Human milk composition is widely studied in relation to these unique abilities, which has led to the identification of various immunomodulating components in human milk, including various bioactive proteins. In addition to proteins, human milk contains free amino acids (FAAs), which have not been well-studied. Of those, the FAAs glutamate and glutamine are by far the most abundant. Levels of these FAAs in human milk sharply increase during the first months of lactation, in contrast to most other FAAs. These unique dynamics are globally consistent, suggesting that their levels in human milk are tightly regulated throughout lactation and, consequently, that they might have specific roles in the developing neonate. Interestingly, free glutamine and glutamate are reported to exhibit immunomodulating capacities, indicating that these FAAs could contribute to neonatal immune development and to the unique protective effects of breastfeeding. This review describes the current understanding of the FAA composition in human milk. Moreover, it provides an overview of the effects of free glutamine and glutamate on immune parameters relevant for allergic sensitization and infections in early life. The data reviewed provide rationale to study the role of free glutamine and glutamate in human milk in the protection against neonatal allergies and infections.
-
5.
Artificial Polymers made of α-amino Acids - Poly(Amino Acid)s, Pseudo-Poly(Amino Acid)s, Poly(Depsipeptide)s, and Pseudo-Proteins.
Zavradashvili, N, Puiggali, J, Katsarava, R
Current pharmaceutical design. 2020;(5):566-593
Abstract
Degradable polymers (DPs) - "green materials" of the future, have an innumerable use in biomedicine, particularly in the fields of tissue engineering and drug delivery. Among these kind of materials naturally occurring polymers - proteins which constituted one of the most important "bricks of life" - α-amino acids (AAs) are highly suitable. A wide biomedical applicability of proteins is due to special properties such as a high affinity with tissues and releasing AAs upon biodegradation that means a nutritive potential for cells. Along with these positive characteristics proteins as biomedical materials they have some shortcomings, such as batch-to-batch variation, risk of disease transmission, and immune rejection. The last limitation is connected with the molecular architecture of proteins. Furthermore, the content of only peptide bonds in protein molecules significantly restricts their material properties. Artificial polymers with the composition of AAs are by far more promising as degradable biomaterials since they are free from the limitations of proteins retaining at the same time their positive features - a high tissue compatibility and nutritive potential. The present review deals with a brief description of different families of AA-based artificial polymers, such as poly(amino acid)s, pseudo-poly(amino acid)s, polydepsipeptides, and pseudo-proteins - relatively new and broad family of artificial AA-based DPs. Most of these polymers have a different macromolecular architecture than proteins and contain various types of chemical links along with NH-CO bonds that substantially expands properties of materials destined for sophisticated biomedical applications.
-
6.
The use of amino acid-based nutritional feeds is effective in the dietary management of pediatric eosinophilic oesophagitis.
Atwal, K, Hubbard, GP, Venter, C, Stratton, RJ
Immunity, inflammation and disease. 2019;(4):292-303
Abstract
INTRODUCTION Eosinophilic oesophagitis (EoE) is an immune-mediated, chronic disease characterized by eosinophilic inflammation and esophageal dysfunction. Specific food allergens including cow's milk protein, are partially causative to disease progression, and dietary management forms three main options; the elemental diet (ED), the empirical elimination diet (EED), and the targeted elimination diet (TED). The dietary choice should be individualized, however, the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines recommend an ED for pediatric EoE with multiple food allergies, failure to thrive, unresponsive disease or unable to follow a highly restricted diet. The aim of this narrative review was to explore the effectiveness of the ED (using amino acid formula [AAF]), in the management of pediatric EoE. METHODS Literature searches were performed to identify eligible studies that described outcomes including eosinophil count, clinical symptoms, growth, and medications. RESULTS Overall, 10 eligible studies were found, with n = 462 patients assigned to receive AAF from a total of n = 748 (average age 6.7 years), for a duration of 4 to 8 weeks. The use of AAF reduced eosinophil levels and demonstrated remission (defined as ≤10 eosinophils per high power field) in 75%-100% of children with improvements, if not resolution, in clinical symptoms. AAF was more clinically effective than the use of the EED or TED, where remission rates were 75%-81% and 40%-69%, respectively. Few studies collected growth outcomes, however where documented these were positive for those on AAF. The long-term impacts of each diet were not thoroughly explored. CONCLUSIONS The use of AAF is a clinically effective management option for pediatric EoE, and further research is required to guide long-term management.
-
7.
d-amino Acids in Health and Disease: A Focus on Cancer.
Bastings, JJAJ, van Eijk, HM, Olde Damink, SW, Rensen, SS
Nutrients. 2019;(9)
Abstract
d-amino acids, the enantiomeric counterparts of l-amino acids, were long considered to be non-functional or not even present in living organisms. Nowadays, d-amino acids are acknowledged to play important roles in numerous physiological processes in the human body. The most commonly studied link between d-amino acids and human physiology concerns the contribution of d-serine and d-aspartate to neurotransmission. These d-amino acids and several others have also been implicated in regulating innate immunity and gut barrier function. Importantly, the presence of certain d-amino acids in the human body has been linked to several diseases including schizophrenia, amyotrophic lateral sclerosis, and age-related disorders such as cataract and atherosclerosis. Furthermore, increasing evidence supports a role for d-amino acids in the development, pathophysiology, and treatment of cancer. In this review, we aim to provide an overview of the various sources of d-amino acids, their metabolism, as well as their contribution to physiological processes and diseases in man, with a focus on cancer.
-
8.
Roles of d-Amino Acids on the Bioactivity of Host Defense Peptides.
Li, H, Anuwongcharoen, N, Malik, AA, Prachayasittikul, V, Wikberg, JE, Nantasenamat, C
International journal of molecular sciences. 2016;(7)
Abstract
Host defense peptides (HDPs) are positively-charged and amphipathic components of the innate immune system that have demonstrated great potential to become the next generation of broad spectrum therapeutic agents effective against a vast array of pathogens and tumor. As such, many approaches have been taken to improve the therapeutic efficacy of HDPs. Amongst these methods, the incorporation of d-amino acids (d-AA) is an approach that has demonstrated consistent success in improving HDPs. Although, virtually all HDP review articles briefly mentioned about the role of d-AA, however it is rather surprising that no systematic review specifically dedicated to this topic exists. Given the impact that d-AA incorporation has on HDPs, this review aims to fill that void with a systematic discussion of the impact of d-AA on HDPs.
-
9.
Review insights into the interactions of amino acids and peptides with inorganic materials using single molecule force spectroscopy.
Das, P, Reches, M
Biopolymers. 2015;(5):480-94
Abstract
Understanding the interactions between proteins and inorganic surfaces is important for the development of new biomaterials and implants as they interface with the immune response by proteins. In addition, the adsorption of proteins to inorganic surfaces leads to the formation of a conditioning layer that facilitates bacterial attachments and biofilm formation. As biofilm provides bacterial resistance to antibiotics, biofilm formation is an undesirable process that could be prevented by resisting protein interactions with the substrate. Moreover, the interaction between proteins and inorganic materials is the basis for the formation of composite materials in nature. Understanding the underlying forces that governs these interactions would lead to the design of new and unique composite materials in vitro. This review focuses on the insights gained using single-molecule force spectroscopy by AFM on these interactions. This tool provides molecular information, at the single molecule level, on the interaction between a molecule on the AFM tip and a substrate.
-
10.
The importance and dosage of amino acids in nutritional support of various pathological conditions in ICU patients.
Pavlickova Aimova, P, Hronek, M, Zadak, Z
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2014;(3):346-55
Abstract
BACKGROUND Normal adults require twenty L-amino acids (AA) for protein synthesis. Functional AA regulate key metabolic pathways that are necessary for maintenance, growth, reproduction and immunity. Dietary supplementation with one or a mixture of these AA may be beneficial for ameliorating health problems at various stages of the life cycle and for optimizing of the efficiency of metabolic transformations. During disease, other amino acids also become essential. The principal goal of protein/amino acid administration in various pathological conditions in intensive care unit (ICU) patients is to provide the precursors of protein synthesis in tissues with high turnover and to protect skeletal muscle mass and function. Amino acid requirements in parenteral nutrition (PN) are higher when the patient is stressed/traumatized/infected than in the unstressed state. In severely ill ICU patients a higher provision of protein and amino acids has been associated with a lower mortality. METHODS AND RESULTS An overview of the effects and dosage of amino acids in nutritional support of various pathological conditions in ICU patients is presented. CONCLUSION It was demonstrated that 2.0-2.5 g protein substrate/kg normal body weight/day is safe and could be optimal for the most critically ill adults to decrease the risk of morbidity and mortality in some pathological conditions.