Cystathionine β-lyase is involved in d-amino acid metabolism

2018 ◽  
Vol 475 (8) ◽  
pp. 1397-1410 ◽  
Author(s):  
Tetsuya Miyamoto ◽  
Masumi Katane ◽  
Yasuaki Saitoh ◽  
Masae Sekine ◽  
Hiroshi Homma
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Acid Metabolism ◽  
Environmental Changes ◽  
Biosynthetic Pathways ◽  
E Coli ◽  
Comparable Level ◽  
Multifunctional Enzymes ◽  
Dehydratase Activity ◽  
Amino Acid Racemase

Non-canonical d-amino acids play important roles in bacteria including control of peptidoglycan metabolism and biofilm disassembly. Bacteria appear to produce non-canonical d-amino acids to adapt to various environmental changes, and understanding the biosynthetic pathways is important. We identified novel amino acid racemases possessing the ability to produce non-canonical d-amino acids in Escherichia coli and Bacillus subtilis in our previous study, whereas the biosynthetic pathways of these d-amino acids still remain unclear. In the present study, we demonstrated that two cystathionine β-lyases (MetC and MalY) from E. coli produce non-canonical d-amino acids including non-proteinogenic amino acids. Furthermore, MetC displayed d- and l-serine (Ser) dehydratase activity. We characterised amino acid racemase, Ser dehydratase and cysteine lyase activities, and all were higher for MetC. Interestingly, all three activities were at a comparable level for MetC, although optimal conditions for each reaction were distinct. These results indicate that MetC and MalY are multifunctional enzymes involved in l-methionine metabolism and the production of d-amino acids, as well as d- and l-Ser metabolism. To our knowledge, this is the first evidence that cystathionine β-lyase is a multifunctional enzyme with three different activities.

scholarly journals Tailoring a Global Iron Regulon to a Uropathogen

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Rajdeep Banerjee ◽  
Erin Weisenhorn ◽  
Kevin J. Schwartz ◽  
Kevin S. Myers ◽  
Jeremy D. Glasner ◽  
...  
Keyword(s):  
Amino Acids ◽  
Urinary Tract ◽  
Amino Acid ◽  
Regulatory Network ◽  
Iron Homeostasis ◽  
Iron Limitation ◽  
Content Type ◽  
E Coli ◽  
General Stress ◽  
K 12

ABSTRACT Pathogenicity islands and plasmids bear genes for pathogenesis of various Escherichia coli pathotypes. Although there is a basic understanding of the contribution of these virulence factors to disease, less is known about variation in regulatory networks in determining disease phenotypes. Here, we dissected a regulatory network directed by the conserved iron homeostasis regulator, ferric uptake regulator (Fur), in uropathogenic E. coli (UPEC) strain CFT073. Comparing anaerobic genome-scale Fur DNA binding with Fur-dependent transcript expression and protein levels of the uropathogen to that of commensal E. coli K-12 strain MG1655 showed that the Fur regulon of the core genome is conserved but also includes genes within the pathogenicity/genetic islands. Unexpectedly, regulons indicative of amino acid limitation and the general stress response were also indirectly activated in the uropathogen fur mutant, suggesting that induction of the Fur regulon increases amino acid demand. Using RpoS levels as a proxy, addition of amino acids mitigated the stress. In addition, iron chelation increased RpoS to the same levels as in the fur mutant. The increased amino acid demand of the fur mutant or iron chelated cells was exacerbated by aerobic conditions, which could be partly explained by the O2-dependent synthesis of the siderophore aerobactin, encoded by an operon within a pathogenicity island. Taken together, these data suggest that in the iron-poor environment of the urinary tract, amino acid availability could play a role in the proliferation of this uropathogen, particularly if there is sufficient O2 to produce aerobactin. IMPORTANCE Host iron restriction is a common mechanism for limiting the growth of pathogens. We compared the regulatory network controlled by Fur in uropathogenic E. coli (UPEC) to that of nonpathogenic E. coli K-12 to uncover strategies that pathogenic bacteria use to overcome iron limitation. Although iron homeostasis functions were regulated by Fur in the uropathogen as expected, a surprising finding was the activation of the stringent and general stress responses in the uropathogen fur mutant, which was rescued by amino acid addition. This coordinated global response could be important in controlling growth and survival under nutrient-limiting conditions and during transitions from the nutrient-rich environment of the lower gastrointestinal (GI) tract to the more restrictive environment of the urinary tract. The coupling of the response of iron limitation to increased demand for amino acids could be a critical attribute that sets UPEC apart from other E. coli pathotypes.

scholarly journals Roles of the C-Terminal Amino Acids of Non-Hexameric Helicases: Insights from Escherichia coli UvrD

2021 ◽  
Vol 22 (3) ◽  
pp. 1018
Author(s):  
Hiroaki Yokota
Keyword(s):  
Escherichia Coli ◽  
Amino Acids ◽  
Amino Acid ◽  
Single Molecule ◽  
Underlying Mechanism ◽  
Amino Acid Sequences ◽  
E Coli ◽  
X Ray Crystallography ◽  
Terminal Amino

Helicases are nucleic acid-unwinding enzymes that are involved in the maintenance of genome integrity. Several parts of the amino acid sequences of helicases are very similar, and these quite well-conserved amino acid sequences are termed “helicase motifs”. Previous studies by X-ray crystallography and single-molecule measurements have suggested a common underlying mechanism for their function. These studies indicate the role of the helicase motifs in unwinding nucleic acids. In contrast, the sequence and length of the C-terminal amino acids of helicases are highly variable. In this paper, I review past and recent studies that proposed helicase mechanisms and studies that investigated the roles of the C-terminal amino acids on helicase and dimerization activities, primarily on the non-hexermeric Escherichia coli (E. coli) UvrD helicase. Then, I center on my recent study of single-molecule direct visualization of a UvrD mutant lacking the C-terminal 40 amino acids (UvrDΔ40C) used in studies proposing the monomer helicase model. The study demonstrated that multiple UvrDΔ40C molecules jointly participated in DNA unwinding, presumably by forming an oligomer. Thus, the single-molecule observation addressed how the C-terminal amino acids affect the number of helicases bound to DNA, oligomerization, and unwinding activity, which can be applied to other helicases.

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

1973 ◽  
Vol 28 (7-8) ◽  
pp. 449-451 ◽  
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.

scholarly journals The Diverse Functions of Non-Essential Amino Acids in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 675 ◽  
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.

IDIOPATHIC HYPERGLYCINEMIA: A NEW DISORDER OF AMINO ACID METABOLISM

PEDIATRICS ◽  
1961 ◽  
Vol 27 (4) ◽  
pp. 539-550 ◽  
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.

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

2019 ◽  
Vol 316 (4) ◽  
pp. E660-E673 ◽  
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.

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

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.

scholarly journals Studies on Requirements for Amino Acids in Infants with Disorders of Amino Acid Metabolism. I. Effect of Alanine

1985 ◽  
Vol 19 (1) ◽  
pp. 86-91 ◽  
Author(s):  
Drew G Kelts ◽  
Denise Ney ◽  
Carolyn Bay ◽  
Jean-Marie Saudubray ◽  
William L Nyhan
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism

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

1998 ◽  
Vol 10 (3) ◽  
pp. 279 ◽  
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.

Sign in / Sign up

Export Citation Format

Share Document