DOCSLIB.ORG

Amino Acids, Glutamine, and Protein Metabolism in Very Low Birth Weight Infants

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

0031-3998/05/5806-1259 PEDIATRIC RESEARCH Vol. 58, No. 6, 2005 Copyright © 2005 International Pediatric Research Foundation, Inc. Printed in U.S.A. Amino Acids, Glutamine, and Protein Metabolism in Very Low Birth Weight Infants PRABHU S. PARIMI, MARK M. KADROFSKE, LOURDES L. GRUCA, RICHARD W. HANSON, AND SATISH C. KALHAN Department of Pediatrics, Schwartz Center for Metabolism and Nutrition, Case Western Reserve University School of Medicine, MetroHealth Medical Center, Cleveland, Ohio, 44109 ABSTRACT Glutamine has been proposed to be conditionally essential for 5 h (AA1.5) resulted in decrease in rate of appearance (Ra) of premature infants, and the currently used parenteral nutrient phenylalanine and urea, but had no effect on glutamine Ra. mixtures do not contain glutamine. De novo glutamine synthesis Infusion of amino acids at 3.0 g/kg/d for 20 h resulted in increase (DGln) is linked to inflow of carbon into and out of the tricar- in DGln, leucine transamination, and urea synthesis, but had no boxylic acid (TCA) cycle. We hypothesized that a higher supply effect on Ra phenylalanine (AA-Ext). These data show an acute of parenteral amino acids by increasing the influx of amino acid increase in parenteral amino acid–suppressed proteolysis, how- carbon into the TCA cycle will enhance the rate of DGln. Very ever, such an effect was not seen when amino acids were infused low birth weight infants were randomized to receive parenteral for 20 h and resulted in an increase in glutamine synthesis. amino acids either 1.5 g/kg/d for 20 h followed by 3.0 g/kg/d for (Pediatr Res 58: 1259–1264, 2005) 5 h (AA1.5) or 3.0 g/kg/d for 20 h followed by 1.5 g/kg/d for 5 h (AA3.0). A third group of babies received amino acids 1.5 g/kg/d Abbreviations for 20 h followed by 3.0 g/kg/d for 20 h (AA-Ext). Glutamine BGln, glutamine derived from proteolysis and protein/nitrogen kinetics were examined using [5-15N]glu- DGln, de novo glutamine synthesis 2 13 15 15 tamine, [ H5]phenylalanine, [1- C, N]leucine, and [ N2]urea TCA, tricarboxylic acid tracers. An acute increase in parenteral amino acid infusion for VLBW, very low birth weight Glutamine participates in a number of key metabolic pro- a higher amount of parenteral amino acids to these VLBW cesses (1) and is also proposed to play an important role in infants enhances the rate of DGln has not been examined. enhancing immune function (2–4). A decrease in plasma glu- Glutamine is synthesized by transamination of ␣-ketogluta- tamine concentration in response to stress (acute illness, burns, rate to glutamate and conversion of glutamate to glutamine. trauma, etc.) suggests that the rate of DGln is unable to keep The latter reaction is catalyzed by glutamine synthase. The pace with the rate of utilization/requirement. This has led sources of carbon skeleton for the synthesis of glutamine, i.e. several investigators to suggest that glutamine is a condition- glutamate and ␣-ketoglutarate, are derived from the amino ally essential amino acid. Studies in adults show that parenteral acids entering the TCA cycle (anaplerosis). An increase influx nutrition supplemented with glutamine decreased both the of these amino acids would be anticipated to result in an morbidity and mortality (5,6). increase in DGln (cataplerosis) (10). Studies in human adults Because the concentration of plasma glutamine is lower in show that supplementation of parenteral nutrition with ana- VLBW infants, and the currently used parenteral nutrient logues of ␣-ketoglutarate enhances the intracellular pool of solutions do not contain glutamine, VLBW premature infants glutamine in the muscle (11,12). We have previously shown were identified as another group of subjects who could poten- that the rate of appearance of glutamine in newborn infants is tially benefit from supplementation of enteral and parenteral positively correlated with whole body rate of protein break- nutrition with glutamine (7–9). However, whether provision of down (13), suggesting that an increased availability of amino acids augments DGln. We hypothesized that supply of a higher Received February 15, 2005; accepted May 10, 2005. amount of parenteral amino acids to clinically stable VLBW Correspondence: Prabhu S. Parimi, M.D., Schwartz Center for Metabolism and Nutri- infants will increase the anaplerotic flux of carbon into the tion, G 735, MetroHealth Medical Center, 2500 MetroHealth Dr., Cleveland, OH 44109; TCA cycle, increase transamination, and accelerate the rate of e-mail: [email protected] This work was supported by National Institutes of Health grant RO1 HD042154 and DGln. We have tested the hypothesis by examining the effect General Clinical Research Center grant RR00080. of parenteral amino acids, either 1.5 g/kg/d or 3 g/kg/d for DOI: 10.1203/01.pdr.0000185130.90205.1f either5hor20h,onglutamine, phenylalanine, leucine nitro- 1259 1260 PARIMI ET AL. gen, and urea kinetics in premature infants Յ32 wk gestation Table 1. Clinical characteristics and Յ1500 g birth weight using a randomized study design. Birth Gestational Age M/F Weight at SNAP weight (g) age (wk) (d) study (g) METHODS AA 1.5 1139 Ϯ 276 29 Ϯ 25Ϯ 1 6/6 1009 Ϯ 270 12 (5–18)* (n ϭ12) Յ Յ Subjects. Preterm infants 32 wk gestation and 1500 g were recruited. AA 3.0 1189 Ϯ 324 28 Ϯ 25Ϯ 1 8/4 1093 Ϯ 308 12 (7–20) After verbal assent from their primary physician, written informed consent was (n ϭ12) obtained from the parent(s), after fully explaining the procedures. The study AA-Ext 1132 Ϯ 289 28 Ϯ 24Ϯ 1 0/5 1035 Ϯ 263 13 (9–21) protocol was approved by the Institutional Review Board. All studies were ϭ performed in the neonatal intensive care unit at MetroHealth Medical Center. (n 5) Premature infants were randomized to receive an initial parenteral nutrition AA1.5: Parenteral amino acids 1.5 g/kg/d for 20 h, 3 g/kg/d for 5 h. AA3.0: ϭ ϭ containing either 1.5 g/kg/d (AA1.5, n 12) or 3 g/kg/d (AA3.0, n 12) of Parenteral amino acids 3 g/kg/d for 20 h, 1.5 g/kg/d for 5 h. AA-Ext: Parenteral amino acids (10% TrophAmine, McGaw, Irvine, CA). After 16 h of amino acid amino acids 1.5 g/kg/d for 20 h, 3 g/kg/d for 20 h. infusion, kinetic studies were performed as described below. Thereafter, the Data shown are mean Ϯ SD. *Median (25–75%). No significant difference amino acid load was increased to 3 g/kg/d in AA1.5 group and decreased to 1.5 g/kg/d in AA3.0 group and infused for the next 5 h, while the infants continued between the groups. to receive isotopic tracer infusion. Because the second part of the study in AA1.5 and AA3.0 groups was only5hascompared with 20 h in the first part, 2 2 15 dover, MA). L-[ H5]phenylalanine (98 atom% H), [ N2]urea (98 atom % a third group (AA-Ext) was also studied where the tracer studies were 15 13 15 13 15 performed after 20 h of amino acid infusion at 1.5 g/kg/d and at 3.0 g/kg/d (Fig. N) and L-[ C, N]leucine (98% C and 98% N) were purchased from 1). Clinical characteristics of the infants and the acuity of illness at birth, Merck & Co. (Dorvall, Canada). Each batch of the tracers was tested for assessed by Scoring of Neonatal Acute Physiology (SNAP), were not different sterility and pyrogenicity as previously described (14). The administered doses 15 ␮ between the study subjects (Table 1). Tracer isotope studies were performed at of various tracers were as follows: L-[5- N]glutamine (prime, 30 mol/kg; ␮ 2 ␮ a mean age of 5 Ϯ 1 d. Infants were on either minimal ventilator support constant rate 30 mol/kg/h, L-[ H5]phenylalanine (prime, 6 mol/kg; constant ␮ 15 ␮ ␮ (defined by FiO Յ35% and mean air way pressure Յ8) (AA1.5, n ϭ 5; AA rate, 4 mol/kg/h), [ N2]urea (prime, 33 mol/kg; constant rate, 3.3 mol/ 2 13 15 ␮ ␮ 3.0, n ϭ 5, AA-Ext, n ϭ 2), or were receiving supplemental oxygen via nasal kg/h) and 1-[ C, N]leucine (prime, 7.5 mol/kg; constant rate, 7.5 mol/ ϳ canula. None of the infants were on insulin or vasopressor support or were kg/h). Blood samples ( 0.7 mL each depending upon the baby’s weight) were receiving corticosteroids. All babies were placed on antibiotics immediately obtained before beginning the tracer infusion and again at 15-min intervals after birth for presumed infection, as per the clinical practice at our institution. between 210 and 240 min. At 240 min, following the last blood sample, the None of the study infants had bacteriologically proven sepsis. Their primary parenteral amino acids solution was changed as described. Another set of blood neonatologist was responsible for all the clinical care including necessary samples were collected between 510 and 540 min. adjustments in intravenous fluids, initiation of parenteral nutrition, and enteral In the AA-Ext group, tracer infusion was begun 16 h after parenteral feeding. None of the infants were receiving enteral feeds at the time of tracer nutrition at 1.5 g/kg/d and continued for 4 h. Blood samples were obtained study. Generally, babies received 10% dextrose water during the first 24 h after between 210 and 240 min, after which the tracer infusion was discontinued, birth and were started on parenteral amino acids between 24 and 72 h of age.
Recommended publications
  • Effects of Dietary L-Glutamine Or L-Glutamine Plus L-Glutamic Acid

    Effects of Dietary L-Glutamine Or L-Glutamine Plus L-Glutamic Acid

    Brazilian Journal of Poultry Science Revista Brasileira de Ciência Avícola Effects of Dietary L-Glutamine or L-Glutamine Plus ISSN 1516-635X Oct - Dec 2015 / Special Issue L-Glutamic Acid Supplementation Programs on the Nutrition - Poultry feeding additives / 093-098 Performance and Breast Meat Yield Uniformity of http://dx.doi.org/10.1590/1516-635xSpecialIssue 42-d-Old Broilers Nutrition-PoultryFeedingAdditives093-098 Author(s) ABSTRACT Ribeiro Jr VIII This study aimed at evaluating four dietary L-Glutamine (L-Gln) Albino LFTI or L-Gln plus L-Glutamate (L-Glu) supplementation programs on the Rostagno HSI Hannas MII performance, breast yield, and uniformity of broilers. A total of 2,112 Ribeiro CLNIII one-d-old male Cobb 500® broilers were distributed according to a Vieira RAIII randomized block design in a 2 × 4 factorial arrangement (L-Gln or L-Gln Araújo WAG deIV Pessoa GBSII plus L-Glu × 4 supplementation programs), totaling eight treatments Messias RKGIII with 12 replicates of 22 broilers each. The supplementation programs Silva DL daIII consisted of the dietary inclusion or not of 0.4% of L-Gln or L-Gln plus L-Glu for four different periods: 0 days (negative control), 9d, 21d, and 42d. Feed intake (FI, g), body weight gain (BWG, g), feed conversion I Federal University of Viçosa, Department ratio (FCR, kg/kg), coefficient of variation of body weight (CV, %), body of Animal Science, Av PH Rolfs S/N, Viçosa 36570-000, MG, Brazil weight uniformity (UNIF, %), breast weight (BW, g), breast yield (BY, II Ajinomoto do Brasil Ind. e Com. de %), coefficient of variation of breast weight (CVB), breast uniformity Alimentos Ltda.
  • Amino Acids Amino Acids

    Amino Acids Amino Acids

    Amino Acids Amino Acids What Are Amino Acids? Essential Amino Acids Non Essential Amino Acids Amino acids are the building blocks of proteins; proteins are made of amino acids. Isoleucine Arginine (conditional) When you ingest a protein your body breaks it down into the individual aminos, Leucine Glutamine (conditional) reorders them, re-folds them, and turns them into whatever is needed by the body at Lysine Tyrosine (conditional) that time. From only 20 amino acids, the body is able to make thousands of unique proteins with different functions. Methionine Cysteine (conditional) Phenylalanine Glycine (conditional) Threonine Proline (conditional) Did You Know? Tryptophan Serine (conditional) Valine Ornithine (conditional) There are 20 different types of amino acids that can be combined to make a protein. Each protein consists of 50 to 2,000 amino acids that are connected together in a specific Histidine* Alanine sequence. The sequence of the amino acids determines each protein’s unique structure Asparagine and its specific function in the body. Asparate Popular Amino Acid Supplements How Do They Benefit Our Health? Acetyl L- Carnitine: As part of its role in supporting L-Lysine: L-Lysine, an essential amino acid, is mental function, Acetyl L-Carnitine may help needed to support proper growth and bone Proteins (amino acids) are needed by your body to maintain muscles, bones, blood, as support memory, attention span and mental development. It can also support immune function. well as create enzymes, neurotransmitters and antibodies, as well as transport and performance. store molecules. N-Acetyl Cysteine: N-Acetyl Cysteine (NAC) is a L-Arginine: L-Arginine is a nonessential amino acid form of the amino acid cysteine.
  • Solutions to 7.012 Problem Set 1

    Solutions to 7.012 Problem Set 1

    MIT Biology Department 7.012: Introductory Biology - Fall 2004 Instructors: Professor Eric Lander, Professor Robert A. Weinberg, Dr. Claudette Gardel Solutions to 7.012 Problem Set 1 Question 1 Bob, a student taking 7.012, looks at a long-standing puddle outside his dorm window. Curious as to what was growing in the cloudy water, he takes a sample to his TA, Brad Student. He wanted to know whether the organisms in the sample were prokaryotic or eukaryotic. a) Give an example of a prokaryotic and a eukaryotic organism. Prokaryotic: Eukaryotic: All bacteria Yeast, fungi, any animial or plant b) Using a light microscope, how could he tell the difference between a prokaryotic organism and a eukaryotic one? The resolution of the light microscope would allow you to see if the cell had a true nucleus or organelles. A cell with a true nucleus and organelles would be eukaryotic. You could also determine size, but that may not be sufficient to establish whether a cell is prokaryotic or eukaryotic. c) What additional differences exist between prokaryotic and eukaryotic organisms? Any answer from above also fine here. In addition, prokaryotic and eukaryotic organisms differ at the DNA level. Eukaryotes have more complex genomes than prokaryotes do. Question 2 A new startup company hires you to help with their product development. Your task is to find a protein that interacts with a polysaccharide. a) You find a large protein that has a single binding site for the polysaccharide cellulose. Which amino acids might you expect to find in the binding pocket of the protein? What is the strongest type of interaction possible between these amino acids and the cellulose? Cellulose is a polymer of glucose and as such has many free hydroxyl groups.
  • Stimulation Effects of Foliar Applied Glycine and Glutamine Amino Acids

    Stimulation Effects of Foliar Applied Glycine and Glutamine Amino Acids

    Open Agriculture. 2019; 4: 164–172 Research Article Yaghoub Aghaye Noroozlo, Mohammad Kazem Souri*, Mojtaba Delshad Stimulation Effects of Foliar Applied Glycine and Glutamine Amino Acids on Lettuce Growth https://doi.org/10.1515/opag-2019-0016 received June 27, 2018; accepted January 20, 2019 1 Introduction Abstract: Amino acids have various roles in plant In biology, amino acids have vital roles in cell life. Amino metabolism, and exogenous application of amino acids acids are among the most important primary metabolites may have benefits and stimulation effects on plant growth within the plant cells. However, they are frequently and quality. In this study, the growth and nutrient uptake regarded as secondary metabolites, particularly in the of Romain lettuce (Lactuca sativa subvar Sahara) were case of proline, glycine and betaine amino acids. Many evaluated under spray of glycine or glutamine at different physiochemical characteristics of plant cells, tissues and concentrations of 0 (as control), 250, 500 and 1000 organs are influenced by the presence of amino acids (Rai mg.L-1, as well as a treatment of 250 mg.L-1 glycine+250 2002; Marschner 2011). They are the building units of mg.L-1 glutamine. The results showed that there was proteins, as the main component of living cells that have significant increase in leaf total chlorophyll content under vital roles in many cell metabolic reactions (Kielland 1994; Gly250+Glu250, Gly250 and Glu1000 mg.L-1treatments, and Rainbird et al. 1984; Jones and Darrah 1993). In addition, in leaf carotenoids content under 250 mg.L-1 glutamine amino acids have various important biological functions spray compared with the control plants.
  • Feedback Inhibition of Fully Unadenylylated Glutamine

    Feedback Inhibition of Fully Unadenylylated Glutamine

    Proc. Natl. Acad. Sci. USA Vol. 90, pp. 4996-5000, June 1993 Biochemistry Feedback inhibition of fully unadenylylated glutamine synthetase from Salmonella typhimurium by glycine, alanine, and serine (x-ray crystaflography/protein structure/effector binding) SHWU-HUEY LIAW, CLARK PAN, AND DAVID EISENBERG* Molecular Biology Institute and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90024 Contributed by David Eisenberg, December 28, 1992 ABSTRACT Bacterial glutamine synthetase (GS; EC the binding of L-glutamate to GS was measured in the 6.3.1.2) was previously shown to be inhibited by nine end presence of ADP and Pi (6, 9). Citing these studies and products of glutamine metabolism. Here we present four unpublished data, Stadtman and Ginsburg (2) concluded crystal structures ofGS, complexed with the substrate Glu and "there are separate sites on the enzyme for alanine, tryp- with each of three feedback inhibitors. The GS of the present tophan, histidine, AMP, and CTP, whereas mutually exclu- study is from Salmonela typhimurium, with Mn2+ ions bound, sive binding occurs between glycine, serine, and alanine" and is fully unadenylylated. From Fourier difference maps, we (P. Z. Smymiotis and E. R. Stadtman, unpublished data find that L-serine, L-alanine, and glycine bind at the site of the cited in review reference 2). And Rhee et al. (11) reviewed substrate L-glutamate. In our model, these four amino acids further evidence for separate sites of inhibition. In short, bind with the atoms they share in common (the "main chain" feedback inhibition ofGS is a complicated regulatory system, +NH3-CH-COO-) in the same positions.
  • Amino Acid Degradation

    Amino Acid Degradation

    BI/CH 422/622 OUTLINE: OUTLINE: Protein Degradation (Catabolism) Digestion Amino-Acid Degradation Inside of cells Protein turnover Dealing with the carbon Ubiquitin Fates of the 29 Activation-E1 Seven Families Conjugation-E2 nitrogen atoms in 20 1. ADENQ Ligation-E3 AA: Proteosome 2. RPH 9 ammonia oxidase Amino-Acid Degradation 18 transamination Ammonia 2 urea one-carbon metabolism free transamination-mechanism to know THF Urea Cycle – dealing with the nitrogen SAM 5 Steps Carbamoyl-phosphate synthetase 3. GSC Ornithine transcarbamylase PLP uses Arginino-succinate synthetase Arginino-succinase 4. MT – one carbon metabolism Arginase 5. FY – oxidase vs oxygenase Energetics Urea Bi-cycle 6. KW – Urea Cycle – dealing with the nitrogen 7. BCAA – VIL Feeding the Urea Cycle Glucose-Alanine Cycle Convergence with Fatty acid-odd chain Free Ammonia Overview Glutamine Glutamate dehydrogenase Overall energetics Amino Acid A. Concepts 1. ConvergentDegradation 2. ketogenic/glucogenic 3. Reactions seen before The SEVEN (7) Families B. Transaminase (A,D,E) / Deaminase (Q,N) Family C. Related to biosynthesis (R,P,H; C,G,S; M,T) 1.Glu Family a. Introduce oxidases/oxygenases b. Introduce one-carbon metabolism (1C) 2.Pyruvate Family a. PLP reactions 3. a-Ketobutyric Family (M,T) a. 1-C metabolism D. Dedicated 1. Aromatic Family (F,Y) a. oxidases/oxygenases 2. a-Ketoadipic Family (K,W) 3. Branched-chain Family (V,I,L) E. Convergence with Fatty Acids: propionyl-CoA 29 N 1 Amino Acid Degradation • Intermediates of the central metabolic pathway • Some amino acids result in more than one intermediate. • Ketogenic amino acids can be converted to ketone bodies.
  • Where Metal Ions Bind in Proteins (Metafloprotein/Protein Structure/Hydrophobicity Contrast Function) MASON M

    Where Metal Ions Bind in Proteins (Metafloprotein/Protein Structure/Hydrophobicity Contrast Function) MASON M

    Proc. Nadl. Acad. Sci. USA Vol. 87, pp. 5648-5652, August 1990 Biophysics Where metal ions bind in proteins (metafloprotein/protein structure/hydrophobicity contrast function) MASON M. YAMASHITA*t, LAURA WESSON*, GEORGE EISENMANt, AND DAVID EISENBERG*§ *Molecular Biology Institute and Department of Chemistry and Biochemistry, and *Department of Physiology, University of California, Los Angeles, CA 90024 Contributed by David Eisenberg, May 14, 1990 ABSTRACT The environments of metal ions (Li', Na', K+, Ag+, Cs+, Mg2+, Ca2+, Mn2+9 Cu2+, Zn2+) in proteins and other metal-host molecules have been examined. Regard- .. 0.00- ______ less ofthe metal and its precise pattern ofligation to the protein, there is a common qualitative feature to the bind site: the metal is ligated by a shell of hydrophilic atomic groups (con- E -0.01 Zn2+ taining oxygen, nitrogen, or sulfur atoms) and this hydrophilic shell is embedded within a larger shell of hydrophobic atomic - -0.02 groups (containing carbon atoms). That is, metals bind at centers of high hydrophobicity contrast. This qualitative ob- servation can be described analytically by the hydrophobicity 0 2 4 6 8 10 contrast function, C, evaluated from the structure. This func- tion is large and positive for a sphere of hydrophilic atomic 0.01 groups (characterized by atomic salvation parameters, Aar, having values < 0) at the center of a larger sphere of hydro- phobic atomic groups (characterized by Aor > 0). In the 23 0.00. metal-binding molecules we have examined, the maximum values of the contrast function lie near to observed metal binding sites. This suggests that the hydrophobicity contrast function may be useful for locating, characterizing, and de- - -0.01 signing metal binding sites in proteins.
  • Effect of Proline and Glutamine on the Functional Properties of Wheat Dough in Winter Wheat Varieties BRENDA C

    Effect of Proline and Glutamine on the Functional Properties of Wheat Dough in Winter Wheat Varieties BRENDA C

    JFS E: Food Engineering and Physical Properties Effect of Proline and Glutamine on the Functional Properties of Wheat Dough in Winter Wheat Varieties BRENDA C. FERMIN, T.S. HAHM, JULIA A. RADINSKY, ROBERT J. KRATOCHVIL, JOHN E. HALL, AND Y. MARTIN LO ABSTRACT: Combinations of proline and glutamine significantly increased the functional properties of soft wheat that were unseen when added individually. To hard wheat, proline contributed more positively than glutamine on most dough and bread properties, which is different from the observations with soft wheat. Addition of glutamine to hard wheat increased the amount of gluten and glutenin after mixing, whereas proline hinders gluten formation despite the increase in glutenin. The ability of proline and glutamine to modify the functional properties of dough and bread appears to be interdependent. Addition of either proline or glutamine appears to have a protective effect on the retention of the other amino acid during breadmaking. Keywords: dough, texture, bread, proline, glutamine Introduction ties of dough have been demonstrated (Mita and Matsumoto 1981; dentification of the biochemical factors responsible for end-use 1984) and later linked to the theory that the intermolecular and in- Iquality variation of wheat is crucial for breeders, producers, tramolecular hydrogen bonding in the gluten complex is responsible grain handlers, millers, and bakers (Dobraszczyk 2001; Graybosch for the viscoelastic nature of dough (Belton 1999). Proline, on the and others 2003). The protein composition in mature wheat has other hand, is composed of about 15% of gliadin, which constitutes been reported to play a critical role in governing wheat flour prop- 30% to 45% of gluten and 10% to 12% of glutenin (55% to 70% of glu- erties and uses (He and Hoseney 1991; Delwiche and others 1998; ten).
  • Amino Acid Catabolism

    Amino Acid Catabolism

    Amino Acid Catabolism • Dietary Proteins • Turnover of Protein • Cellular protein • Deamination • Urea cycle • Carbon skeletons of amino acids Amino Acid Metabolism •Metabolism of the 20 common amino acids is considered from the origins and fates of their: (1) Nitrogen atoms (2) Carbon skeletons •For mammals: Essential amino acids must be obtained from diet Nonessential amino acids - can be synthesized Amino Acid Catabolism • Amino acids from degraded proteins or from diet can be used for the biosynthesis of new proteins • During starvation proteins are degraded to amino acids to support glucose formation • First step is often removal of the α-amino group • Carbon chains are altered for entry into central pathways of carbon metabolism Dietary Proteins • Digested in intestine • by peptidases • transport of amino acids • active transport coupled with Na+ Protein Turnover • Proteins are continuously synthesized and degraded (turnover) (half-lives minutes to weeks) • Lysosomal hydrolysis degrades some proteins • Some proteins are targeted for degradation by a covalent attachment (through lysine residues) of ubiquitin (C terminus) • Proteasome hydrolyzes ubiquitinated proteins Turnover of Protein • Cellular protein • Proteasome degrades protein with Ub tags • T 1/2 determined by amino terminus residue • stable: ala, pro, gly, met greater than 20h • unstable: arg, lys, his, phe 2-30 min Ubibiquitin • Ubiquitin protein, 8.5 kD • highly conserved in yeast/humans • carboxy terminal attaches to ε-lysine amino group • Chains of 4 or more Ub molecules
  • The Emerging Role of Amino Acids of the Brain Microenvironment in the Process of Metastasis Formation

    The Emerging Role of Amino Acids of the Brain Microenvironment in the Process of Metastasis Formation

    cancers Review The Emerging Role of Amino Acids of the Brain Microenvironment in the Process of Metastasis Formation Francesca Cutruzzolà †, Amani Bouzidi †, Francesca Romana Liberati, Sharon Spizzichino, Giovanna Boumis, Alberto Macone , Serena Rinaldo , Giorgio Giardina and Alessio Paone * Laboratory Affiliated to Istituto Pasteur Italia, Department of Biochemical Sciences A. Rossi Fanelli, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy; [email protected] (F.C.); [email protected] (A.B.); [email protected] (F.R.L.); [email protected] (S.S.); [email protected] (G.B.); [email protected] (A.M.); [email protected] (S.R.); [email protected] (G.G.) * Correspondence: [email protected]; Tel.: +39-0649910713 † These authors contributed equally to the work. Simple Summary: Why some cancers choose to form metastases in one organ rather than another is still largely unknown. In this review, we summarized the available information on the possible mechanisms controlling this choice. In particular, we tried to understand how some molecules, especially amino acids, released into the environment outside the cells, participate in selecting the brain as a target organ for the formation of metastases by specific types of aggressive tumors such as melanoma, breast, and lung cancer. Abstract: Brain metastases are the most severe clinical manifestation of aggressive tumors. Melanoma, Citation: Cutruzzolà, F.; Bouzidi, A.; breast, and lung cancers are the types that prefer the brain as a site of metastasis formation, even if the Liberati, F.R.; Spizzichino, S.; Boumis, reasons for this phenomenon still remain to be clarified. One of the main characteristics that makes a G.; Macone, A.; Rinaldo, S.; Giardina, cancer cell able to form metastases in the brain is the ability to interact with the endothelial cells of the G.; Paone, A.
  • The Diverse Functions of Non-Essential Amino Acids in Cancer

    The Diverse Functions of Non-Essential Amino Acids in Cancer

    cancers Review The Diverse Functions of Non-Essential Amino Acids in Cancer Bo-Hyun Choi and Jonathan L. Coloff * Department of Physiology and Biophysics, University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA; [email protected] * Correspondence: coloff@uic.edu Received: 16 April 2019; Accepted: 10 May 2019; Published: 15 May 2019 Abstract: 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. Keywords: aspartate; asparagine; arginine; cysteine; glutamate; glutamine; glycine; proline; serine; cancer 1. Introduction It is now well established that tumors display different metabolic phenotypes than normal tissues [1]. The first observed and most studied metabolic phenotype of tumors is that of increased glucose uptake and glycolysis [2,3], a metabolic phenotype that is exploited in the clinic to image human tumors and metastases via 18flurodeoxyglucose positron emission tomography (18FDG-PET) [4].
  • The Effects of L-Glutamate, L-Glutamine, and L-Aspartic Acid on the Amylase Production of E

    The Effects of L-Glutamate, L-Glutamine, and L-Aspartic Acid on the Amylase Production of E

    Journal of Emerging Investigators The Effects of L-glutamate, L-glutamine, and L-aspartic Acid on the Amylase Production of E. coli Transformed with pAmylase Kevin S. Liu and Brittany Franckowiak Wilde Lake High School, Howard County, MD Summary glands, hydrolyzes dietary starch into disaccharides Amylase catalyzes the hydrolysis of dietary starch into and trisaccharides. These saccharides are further oligosaccharides. In humans, amylase is produced by the converted by other enzymes to glucose and used as pancreas and salivary glands and is important in food a source of cellular energy (1). Consequently, amylase digestion. Human amylase also has broad applications for has an important role in digestion, where the secretion of therapeutic use in patients with pancreatic insufficiency, necessitating an efficient process for amylase production. amylase is vital to proper nutrient digestion and absorption E. coli transfected with human amylase cDNA can be (2, 3). Abnormal or unhealthy enzyme secretion by the used to produce amylase to fulfill these pharmaceutical pancreas can result in nutrient malabsorption and other production needs. It was reported that the production symptoms that lead to malnutrition (4). of Thermus maltogenic amylase in E. coli is enhanced by In addition to their role in digestion, amylases are also adding L-glutamate and L-glutamine. The purpose of this important ingredients in the food industry. Specifically, experiment was to determine whether the amino acids alpha and beta amylases are used in brewing beers and L-glutamate, L-glutamine, and L-aspartic acid could liquors made from starch-derived sugars. Amylases, increase human amylase expression in E. coli.