Amino Acid Metabolism in Human Embryos

The aim of this study was to find some relationship between amino acid metabolism and the embryo morphokinetic parameters studied via time-lapse analysis. Study included 48 human embryo samples and their culture media. Two groups of embryos were identified: embryos reached the 8-cell stage on day 3 (n=34) and embryos failed to develop at any point during the incubation (n=14). Amino acids levels were measured on day 3 of embryo development; using time-lapse analysis, the precise timing of embryo cleavage, synchrony of division, grade of fragmentation etc. were established. No statistically significant differences between dividing and arresting embryos were observed in terms of amino acids production/consumption and turnover. Amino acids which were part of the culture medium did not exhibit any statistically significant correlation with kinetic parameters with the exception of the grade of fragmentation on day 3; there were negative correlation with glutamate, and positive with glutamine, glycine and taurine. In some dividing and in some arresting embryos appeared new amino acids which strongly correlated with each other, with methionine, but not with any other amino acid that is a regular part of the culture medium.

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Metabolic profile of in vitro derived human embryos is not affected by the mode of fertilization

MHR Basic science of reproductive medicine ◽

10.1093/molehr/gaaa015 ◽

2020 ◽

Vol 26 (4) ◽

pp. 277-287

Author(s):

Christine Leary ◽

Roger G Sturmey

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Metabolic Profile ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Human Embryos ◽

Embryo Morphology ◽

Male Factor ◽

Triglyceride Content

Abstract The pattern of metabolism by early embryos in vitro has been linked to a range of phenotypes, including viability. However, the extent to which metabolic function of embryos is modified by specific methods used during ART has yet to be fully described. This study has sought to determine if the mode of fertilization used to create embryos affects subsequent embryo metabolism of substrates. A metabolic profile, including consumption of key substrates and the endogenous triglyceride content of individual IVF and ICSI supernumerary embryos, was assessed and compared. Embryo development and quality was also recorded. All embryos were donated at a single clinical IVF center, on Day 5, from 36 patients aged 18–38 years, The data revealed that consumption of glucose and pyruvate, and production of lactate, did not differ between embryos created by IVF or ICSI. Similarly, the mode of insemination did not impact on the triglyceride content of embryos. However, ICSI-derived embryos displayed a more active turnover of amino acids (P = 0.023), compared to IVF embryos. The specific amino acids produced in higher quantities from ICSI compared to IVF embryos were aspartate (P = 0.016), asparagine (P = 0.04), histidine (P = 0.021) and threonine (P = 0.009) while leucine consumption was significantly lower (P = 0.04). However, importantly neither individual nor collective differences in amino acid metabolism were apparent for sibling oocytes subjected to either mode of fertilization. Embryo morphology (the number of top grade embryos) and development (proportion reaching the blastocyst stage) were comparable in patients undergoing IVF and ICSI. In conclusion, the microinjection of spermatozoa into oocytes does not appear to have an impact on subsequent metabolism and viability. Observed differences in amino acid metabolism may be attributed to male factor infertility of the patients rather than the ICSI procedure per se.

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Amino acid metabolism of bovine blastocysts derived from parthenogenetically activated or in vitro fertilized oocytes

Reproduction Fertility and Development ◽

10.1071/r98052 ◽

1998 ◽

Vol 10 (3) ◽

pp. 279 ◽

Cited By ~ 10

Author(s):

Y. G. Jung ◽

T. Sakata ◽

E. S. Lee ◽

Y. Fukui

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Amino Acid Metabolism ◽

Culture Medium ◽

Acid Metabolism ◽

Essential Amino Acids ◽

Fluid Medium ◽

Vitro Fertilization ◽

Oviduct Fluid

The uptake and synthesis of 19 amino acids by fresh or frozen–thawed bovine blastocysts produced by parthenogenesis (PT) or in vitro fertilization (IVF) were compared in the present study. Fresh blastocysts, 180 h after IVF or PT activation, and frozen–thawed blastocysts, 168 h old and cultured for 12 h post-thawing, were cultured in synthetic oviduct fluid medium (SOFM) containing polyvinyl alcohol (PVA) with both essential and non-essential amino acids (EAA and NEAA, respectively) (Medium 1: M1) or SOFM containing PVA with only EAA (Medium 2: M2). In Experiment 1, when fresh or frozen–thawed PT blastocysts were cultured in M1, the uptake of glutamate (in fresh only), aspartate and arginine, and the synthesis of glutamine and alanine were significantly enhanced. In the culture with M2, serine, asparagine, glutamate, glutamine, glycine, arginine and alanine were significantly taken up. It was found that the glutamine concentrations was significantly higher (P < 0.001) in the culture medium drops containing embryos than in the drops without embryos. In Experiment 2, when PT blastocysts were cultured in M1, the uptake of aspartate and synthesis of alanine were greater (P < 0.01) than those by IVF blastocysts. When M2 was used, a significant (P < 0.01) production of serine, asparagine, glutamate, glutamine and alanine, and the uptake of arginine by PT blastocysts were observed. In Experiment 3, when IVF blastocysts were cultured in M1, fresh blastocysts depleted more aspartate and glutamate, and produced more glutamine and alanine than frozen–thawed blastocysts. When cultured in M2, frozen–thawed blastocysts depleted more threonine (P < 0.01) than fresh blastocysts. These results indicate that the uptake and synthesis of amino acids were different in fresh or frozen–thawed bovine blastocysts derived from PT or IVF. These differences in amino acid metabolism may be related to the viability of the blastocysts.

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Metabolic activity of human blastocysts correlates with their morphokinetics, morphological grade, KIDScore and artificial intelligence ranking

Human Reproduction ◽

10.1093/humrep/deaa181 ◽

2020 ◽

Vol 35 (9) ◽

pp. 2004-2016

Author(s):

Laura Ferrick ◽

Yee Shan Lisa Lee ◽

David K Gardner

Keyword(s):

Artificial Intelligence ◽

Amino Acids ◽

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Glucose Consumption ◽

Time Lapse ◽

Total Amino Acid ◽

Embryo Viability ◽

Developmental Potential

Abstract STUDY QUESTION Is there a relationship between blastocyst metabolism and biomarkers of embryo viability? SUMMARY ANSWER Blastocysts with higher developmental potential and a higher probability of resulting in a viable pregnancy consume higher levels of glucose and exhibit distinct amino acid profiles. WHAT IS KNOWN ALREADY Morphological and morphokinetic analyses utilized in embryo selection provide insight into developmental potential, but alone are unable to provide a direct measure of embryo physiology and inherent health. Glucose uptake is a physiological biomarker of viability and amino acid utilization is different between embryos of varying qualities. STUDY DESIGN, SIZE, DURATION Two hundred and nine human preimplantation embryos from 50 patients were cultured in a time-lapse incubator system in both freeze all and fresh transfer cycles. A retrospective analysis of morphokinetics, morphology (Gardner grade), KIDScore, artificial intelligence grade (EmbryoScore), glucose and amino acid metabolism, and clinical pregnancies was conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS ICSI was conducted in all patients, who were aged ≤37 years and previously had no more than two IVF cycles. Embryos were individually cultured in a time-lapse incubator system, and those reaching the blastocyst stage had their morphokinetics annotated and were each assigned a Gardner grade, KIDScore and EmbryoScore. Glucose and amino acid metabolism were measured. Clinical pregnancies were confirmed by the presence of a fetal heartbeat at 6 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE Glucose consumption was at least 40% higher in blastocysts deemed of high developmental potential using either the Gardner grade (P < 0.01, n = 209), KIDScore (P < 0.05, n = 207) or EmbryoScore (P < 0.05, n = 184), compared to less viable blastocysts and in blastocysts that resulted in a clinical pregnancy compared to those that failed to implant (P < 0.05, n = 37). Additionally, duration of cavitation was inversely related to glucose consumption (P < 0.05, n = 200). Total amino acid consumption was significantly higher in blastocysts with an EmbryoScore higher than the cohort median score (P < 0.01, n = 185). Furthermore, the production of amino acids was significantly lower in blastocysts with a high Gardner grade (P < 0.05, n = 209), KIDScore (P < 0.05, n = 207) and EmbryoScore (P < 0.01, n = 184). LIMITATIONS, REASONS FOR CAUTION Samples were collected from patients who had ICSI treatment and from only one clinic. WIDER IMPLICATIONS OF THE FINDINGS These results confirm that metabolites, such as glucose and amino acids, are valid biomarkers of embryo viability and could therefore be used in conjunction with other systems to aid in the selection of a healthy embryo. STUDY FUNDING/COMPETING INTEREST(S) Work was supported by Virtus Health. D.K.G is contracted with Virtus Health. The other authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER N/A.

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Biochemische Aspekte des Aminosäuren-Stoffwechsels bei Psoriasis vulgaris / Biochemical Aspects of Amino Acid Metabolism in Psoriasis vulgaris

Zeitschrift für Naturforschung C ◽

10.1515/znc-1973-7-816 ◽

1973 ◽

Vol 28 (7-8) ◽

pp. 449-451 ◽

Cited By ~ 2

Author(s):

G. Peter ◽

H. Angst ◽

U. Koch

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Free Amino Acids ◽

Free Amino ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Psoriasis Vulgaris ◽

Normal Subjects ◽

Pathological Process

Free and protein-bound amino acids in serum and scales were investigated. In serum the bound amino acids of psoriatics are significantly higher with exception of Pro, Met, Tyr and Phe in contrast to normal subjects. For free amino acids the differences between normal subjects and psoriatics found in serum and scales are not significant. Results are discussed in relation to the single amino acids and the biochemical correlations are outlined which takes the pathological process as a basis.

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The Diverse Functions of Non-Essential Amino Acids in Cancer

Cancers ◽

10.3390/cancers11050675 ◽

2019 ◽

Vol 11 (5) ◽

pp. 675 ◽

Cited By ~ 25

Author(s):

Bo-Hyun Choi ◽

Jonathan L. Coloff

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Cancer Therapy ◽

Metabolic Pathways ◽

Essential Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Essential Amino Acids ◽

Redox Status ◽

Antioxidant Systems

Far beyond simply being 11 of the 20 amino acids needed for protein synthesis, non-essential amino acids play numerous important roles in tumor metabolism. These diverse functions include providing precursors for the biosynthesis of macromolecules, controlling redox status and antioxidant systems, and serving as substrates for post-translational and epigenetic modifications. This functional diversity has sparked great interest in targeting non-essential amino acid metabolism for cancer therapy and has motivated the development of several therapies that are either already used in the clinic or are currently in clinical trials. In this review, we will discuss the important roles that each of the 11 non-essential amino acids play in cancer, how their metabolic pathways are linked, and how researchers are working to overcome the unique challenges of targeting non-essential amino acid metabolism for cancer therapy.

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Postharvest changes in ammonium, amino acids and enzymes of amino acid metabolism in asparagus spear tips

Journal of the Science of Food and Agriculture ◽

10.1002/jsfa.2740630414 ◽

1993 ◽

Vol 63 (4) ◽

pp. 465-471 ◽

Cited By ~ 36

Author(s):

Paul L. Hurst ◽

Christopher J. Clark

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism

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P–283 Combination between amino acids profile of the spent culture media and morphokinetics parameters of human embryos to determine its viability

Human Reproduction ◽

10.1093/humrep/deab130.282 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

N Adel ◽

M Kadah ◽

S Abdulghafar ◽

M Elmahdy ◽

D Ghareeb ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Embryo Development ◽

Culture Medium ◽

Essential Amino Acids ◽

Human Embryos ◽

Data Set ◽

Group A ◽

Amino Acids Profile ◽

Group D

Abstract Study question How to determine human embryo viability noninvasively before embryo transfer? Summary answer We propose that the combination of the amino acid profile of an individual embryo with its morphokinetics will provide noninvasive tool to determine its viability. What is known already It was already known that human embryos at early cleavage require non-essential amino acids, while at the 8-cell to blastocyst stages, a mixture of non-essential and essential amino acids. Amino acids have important roles during embryo development. Acting as biosynthetic precursors,buffers of intracellular pH in the embryo, antioxidants, energy sources and regulators of metabolic function and signaling pathways. Many studies have used time-lapse to analyze human embryonic development including the process of fertilization and assessment of early events and introducednoninvasive prognostic markers which predict embryo development and correlate it to IVF treatment outcomes. Study design, size, duration This study was a prospective cohort study approved by the Clinical Trial Ethical Committee of Faculty of Medicine, Alexandria University according to ethical standards of scientific research (Serial number: 0303721).Thirty females aged 30.13 ± 4.83 years undergoing ICSI cycle in the Madina Fertility Center, during the period of March 2018 to November 2019.202 MII oocytes were incubated individually in embryoscope. Participants/materials, setting, methods Embryos (n = 161) were divided on Day 5 into two groups –developed embryos “Group D” (embryos that developed to blastocyst) and arrested embryos “Group A” (embryos remain at cleavage stage and fail to develop to blastocys).Developed embryos (Group D) included 99 embryos, and Arrested embryos (Group A) included 62 embryos. For each group, morphokinetic developmental points using embryoscope and the different amino acids concentrations in spent culture medium were analyzed using LC- mass spectro etry. Main results and the role of chance On one hand, the first appearance of pronuclei (TPNa), t2, t4 and CC2 in group D occurred significantly earlier than those of Group A.Analysis of 19 essential and non-essential amino acids in spent culture medium of each embryo in the two studied groups D and A showed a significantly higher concentration of two essential amino acids L-Valine (145.73 ± 150.96) and L-Phenylalanine (61.59 ± 55.78) in Group D than their concentration in Group A ( 104.58 ± 33.58, 44.24 ± 14.61, respectively , p ≤ 0.05).and significantly lower concentration of three non-essential amino acids L-Tyrosine (62.56 ± 41.03) , L-Cysteine (19.48 ± 11.90), and L-Alanine (136.0 ± 389.83) observed in Group D when compared to Group A (69.57 ± 20.78, 22.37 ± 8.59,145.33 ± 165.22, respectively, Limitations, reasons for caution It is important to note, that results were developed on a data set from one clinic with different stimulation protocols, a multicenter data and a correlation with the stimulation protocol used should be involved in future studies, in addition a larger sample size to avoid high standard deviation is recommended Wider implications of the findings: We can conclude that amino acid turnover is independent of the traditional morphological assessment of embryos and it may reflect its viability. The prospective combined use of amino acids profile of individual embryo and its morphokinetic parameters may contribute to introduce a new noninvasivs tool that may improve implantation rate Trial registration number 0303721

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IDIOPATHIC HYPERGLYCINEMIA: A NEW DISORDER OF AMINO ACID METABOLISM

PEDIATRICS ◽

10.1542/peds.27.4.539 ◽

1961 ◽

Vol 27 (4) ◽

pp. 539-550 ◽

Cited By ~ 1

Author(s):

William L. Nyhan ◽

Margaret Borden ◽

Barton Childs

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Oral Administration ◽

Dietary Intake ◽

Urinary Excretion ◽

Cation Exchange ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Acute Illness ◽

Progressive Decrease

The amino acids of blood and urine have been investigated using chromatography on cation exchange columns in the study of a patient with idiopathic hyperglycinemia. Marked increases in concentrations of glycine, serine, alanine, isoleucine and valine were found in the plasma. These changes were not reflected in increased excretion of these amino acids in the urine (with the exception of glycine). Restriction of the dietary intake of protein resulted in a decrease in the concentrations of glycine and other amino acids in the blood and urine, and there was a concomitant decrease in the frequency and severity of episodes of acute illness. The oral administration of leucine was found to induce a decrease in the levels of a number of amino acids in the patient and in controls. Continued decrease during the 3 hours of observation was noted for serine, isoleucine and valine. A mild but progressive decrease in threonine concentration was observed in the controls, while in the patient the concentration increased after the administration of leucine. Decreased levels at 1½ hours, returning toward the fasting levels at 3 hours, were observed for alanine, taurine and glycine. These apparently normal responses to leucine loads were not mediated through increase in the urinary excretion of the amino acids involved, and the data are interpreted to indicate entry of these amino acids into cells.

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Glucose and amino acid metabolism in mice depend mutually on glucagon and insulin receptor signaling

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00410.2018 ◽

2019 ◽

Vol 316 (4) ◽

pp. E660-E673 ◽

Cited By ~ 10

Author(s):

Katrine D. Galsgaard ◽

Marie Winther-Sørensen ◽

Jens Pedersen ◽

Sasha A. S. Kjeldsen ◽

Mette M. Rosenkilde ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Insulin Receptor ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Receptor Signaling ◽

Cell Secretion ◽

Glucagon Receptor ◽

Insulin Receptor Signaling ◽

Glucagon And Insulin

Glucagon and insulin are important regulators of blood glucose. The importance of insulin receptor signaling for alpha-cell secretion and of glucagon receptor signaling for beta-cell secretion is widely discussed and of clinical interest. Amino acids are powerful secretagogues for both hormones, and glucagon controls amino acid metabolism through ureagenesis. The role of insulin in amino acid metabolism is less clear. Female C57BL/6JRj mice received an insulin receptor antagonist (IRA) (S961; 30 nmol/kg), a glucagon receptor antagonist (GRA) (25-2648; 100 mg/kg), or both GRA and IRA (GRA + IRA) 3 h before intravenous administration of similar volumes of saline, glucose (0.5 g/kg), or amino acids (1 µmol/g) while anesthetized with isoflurane. IRA caused basal hyperglycemia, hyperinsulinemia, and hyperglucagonemia. Unexpectedly, IRA lowered basal plasma concentrations of amino acids, whereas GRA increased amino acids, lowered glycemia, and increased glucagon but did not influence insulin concentrations. After administration of GRA + IRA, insulin secretion was significantly reduced compared with IRA administration alone. Blood glucose responses to a glucose and amino acid challenge were similar after vehicle and GRA + IRA administration but greater after IRA and lower after GRA. Anesthesia may have influenced the results, which otherwise strongly suggest that both hormones are essential for the maintenance of glucose homeostasis and that the secretion of both is regulated by powerful negative feedback mechanisms. In addition, insulin limits glucagon secretion, while endogenous glucagon stimulates insulin secretion, revealed during lack of insulin autocrine feedback. Finally, glucagon receptor signaling seems to be of greater importance for amino acid metabolism than insulin receptor signaling.

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