Transamination What Is Transamination? Subhadipa 2020 • Important Method of Nitrogen Metabolism of Amino Acids
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Detection and Formation Scenario of Citric Acid, Pyruvic Acid, and Other Possible Metabolism Precursors in Carbonaceous Meteorites
Detection and formation scenario of citric acid, pyruvic acid, and other possible metabolism precursors in carbonaceous meteorites George Coopera,1, Chris Reeda, Dang Nguyena, Malika Cartera, and Yi Wangb aExobiology Branch, Space Science Division, National Aeronautics and Space Administration-Ames Research Center, Moffett Field, CA 94035; and bDevelopment, Planning, Research, and Analysis/ZymaX Forensics Isotope, 600 South Andreasen Drive, Suite B, Escondido, CA 92029 Edited by David Deamer, University of California, Santa Cruz, CA, and accepted by the Editorial Board July 1, 2011 (received for review April 12, 2011) Carbonaceous meteorites deliver a variety of organic compounds chained three-carbon (3C) pyruvic acid through the eight-carbon to Earth that may have played a role in the origin and/or evolution (8C) 7-oxooctanoic acid and the branched 6C acid, 3-methyl- of biochemical pathways. Some apparently ancient and critical 4-oxopentanoic acid (β-methyl levulinic acid), Fig. 1, Table S1. metabolic processes require several compounds, some of which 2-methyl-4-oxopenanoic acid (α-methyl levulinic acid) is tenta- are relatively labile such as keto acids. Therefore, a prebiotic setting tively identified (i.e., identified by mass spectral interpretation for any such individual process would have required either a only). As a group, these keto acids are relatively unusual in that continuous distant source for the entire suite of intact precursor the ketone carbon is located in a terminal-acetyl group rather molecules and/or an energetic and compact local synthesis, parti- than at the second carbon as in most of the more biologically cularly of the more fragile members. -
Lecture: 28 TRANSAMINATION, DEAMINATION and DECARBOXYLATION
Lecture: 28 TRANSAMINATION, DEAMINATION AND DECARBOXYLATION Protein metabolism is a key physiological process in all forms of life. Proteins are converted to amino acids and then catabolised. The complete hydrolysis of a polypeptide requires mixture of peptidases because individual peptidases do not cleave all peptide bonds. Both exopeptidases and endopeptidases are required for complete conversion of protein to amino acids. Amino acid metabolism The amino acids not only function as energy metabolites but also used as precursors of many physiologically important compounds such as heme, bioactive amines, small peptides, nucleotides and nucleotide coenzymes. In normal human beings about 90% of the energy requirement is met by oxidation of carbohydrates and fats. The remaining 10% comes from oxidation of the carbon skeleton of amino acids. Since the 20 common protein amino acids are distinctive in terms of their carbon skeletons, amino acids require unique degradative pathway. The degradation of the carbon skeletons of 20 amino acids converges to just seven metabolic intermediates namely. i. Pyruvate ii. Acetyl CoA iii. Acetoacetyl CoA iv. -Ketoglutarate v. Succinyl CoA vi. Fumarate vii. Oxaloacetate Pyruvate, -ketoglutarate, succinyl CoA, fumarate and oxaloacetate can serve as precursors for glucose synthesis through gluconeogenesis.Amino acids giving rise to these intermediates are termed as glucogenic. Those amino acids degraded to yield acetyl CoA or acetoacetate are termed ketogenic since these compounds are used to synthesize ketone bodies. Some amino acids are both glucogenic and ketogenic (For example, phenylalanine, tyrosine, tryptophan and threonine. Catabolism of amino acids The important reaction commonly employed in the breakdown of an amino acid is always the removal of its -amino group. -
Aqueous Phase Photochemistry of Α-Keto Acids As a Function of Ph
Aqueous Phase Photochemistry of α-Keto Acids as a Function of pH Michael Ryan Dooley Department of Chemistry and Biochemistry University of Colorado at Boulder March 21 2017 Advisor: Dr. Veronica Vaida, Department of Chemistry and Biochemistry Committee: Dr. Veronica Vaida, Department of Chemistry and Biochemistry Dr. Robert Parson, Department of Chemistry and Biochemistry Dr. Chris Bowman, Department of Chemical and Biological Engineering 1 Tables of Contents Abstract……………………………………………………………………………………..page 2 Introduction…………………………………………………………………………………page 2 Experimental Methods………………………………………………………………….…..page 9 Materials……………………………………………………………………….……page 9 Titration – Debye-Huckel Extended Method……………………………………….page 9 Photolysis of Pyruvic Acid……………………………...…………………………page 11 Ultraviolet-Visible Spectroscopy……………………………………….…………page 12 1HNMR…………………………………………………………………………….page 12 Electrospray Ionization Mass Spectrometry……………..………………………...page 13 Results and Discussion…………………………………………...………………..………page 13 Determination of Acid Dissociation Constants…………………………………….page 13 Dependence of Keto-Diol Ratio on pH…………………………………………….page 16 Dark Processing of Pre-Photolysis Solutions…………………………………..….page 18 Photolysis of Pyruvic Acid………………………………….……………………..page 21 Conclusions and Future Directions…………...…………………………………………....page 27 References…………………………………………………………………….……………page 29 2 Abstract α-Keto acids react in solution in the presence of sunlight to form complex organic oligomers that can contribute to the formation of organic atmospheric aerosols. -
Transamination in Tumors, Fetal Tissues, and Regenerating Liver* Philip P
Transamination in Tumors, Fetal Tissues, and Regenerating Liver* Philip P. Cohen, M.D., and G. Leverne Hekhuis (From the Laboratory o~ Physiological Chemistry, Yale University School of Medicine, New Haven, Connecticut) (Received for publication June 9, I94I) von Euler and co-workers (22), on the basis of TISSUE SOURCES results of essentially qualitative experiments, first re- Tumors.--The mouse tumors employed in this in- ported that the transaminase activity ot~ tumors was vestigation were the following: low. These investigators, using Jensen sarcoma and normal muscle, measured the rate of disappearance of I. United States Public Health Service No. ~7-- oxaloacetic acid in the following reaction: originally described as a neuroepithelioma (20). 1 2. Sarcoma 37 .1 3. Yale No. xuan estrogen-induced ,) 1( + )-glutamic acid + oxaloacetic acid a mammary adenocarcinoma (5). 1 4. No. x5o9I-A - ~'b a-ketoglutaric acid + aspartic acid spontaneous mammary medullary adenocarcinoma In addition to studies of reaction I in tumors, Braun- (6) "1 5- No. 42--glioblastoma multiforme. 2 6. No. stein and Azarkh (2) studied the reaction: i o8--rhabdomyosarcoma. 2 The tumors were transplanted at regular intervals 2) glutamic acid+a-keto acid to insure a uniform supply. a-ketoglutaric acid + amino acid "-b- Fetal, kitten, and adult cat tissues.--Two pregnant cats provided the fetal tissue. The length of the preg- The amino acids investigated in the case of reaction nancy was uncertain, but was estimated to be in the 2b were the d- and l-forms of alanine, valine, leucine, last trimester in both instances. Hemihysterectomies and isoleucine. The rate of reaction za in which both were performed under nembutal anesthesia and 2 d(--)- and l(+)-glutamic acid were used, plus fetuses removed from each animal. -
Lecture 11 - Biosynthesis of Amino Acids
Lecture 11 - Biosynthesis of Amino Acids Chem 454: Regulatory Mechanisms in Biochemistry University of Wisconsin-Eau Claire 1 Introduction Biosynthetic pathways for amino acids, Text nucleotides and lipids are very old Biosynthetic (anabolic) pathways share common intermediates with the degradative (catabolic) pathways. The amino acids are the building blocks for proteins and other nitrogen-containing compounds 2 2 Introduction Nitrogen Fixation Text Reducing atmospheric N2 to NH3 Amino acid biosynthesis pathways Regulation of amino acid biosynthesis. Amino acids as precursors to other biological molecules. e.g., Nucleotides and porphoryns 3 3 Introduction Nitrogen fixation is carried out by a few Text select anaerobic micororganisms The carbon backbones for amino acids come from glycolysis, the citric acid cycle and the pentose phosphate pathway. The L–stereochemistry is enforced by transamination of α–keto acids 4 4 1. Nitrogen Fixation Microorganisms use ATP and ferredoxin to Text reduce atmospheric nitrogen to ammonia. 60% of nitrogen fixation is done by these microorganisms 15% of nitrogen fixation is done by lighting and UV radiation. 25% by industrial processes Fritz Habers (500°C, 300!atm) N2 + 3 H2 2 N2 5 5 1. Nitrogen Fixation Enzyme has both a reductase and a Text nitrogenase activity. 6 6 1.1 The Reductase (Fe protein) Contains a 4Fe-4S Text center Hydrolysis of ATP causes a conformational change that aids the transfer of the electrons to the nitrogenase domain (MoFe protein) 7 7 1.1 The Nitrogenase (MoFe Protein) The nitrogenase Text component is an α2β2 tetramer (240#kD) Electrons enter the P-cluster 8 8 1.1 The Nitrogenase (MoFe Protein) An Iron-Molybdenum cofactor for the Text nitrogenase binds and reduces the atmospheric nitrogen. -
Chem 352 - Lecture 10, Part II Citric Acid Cycle
Chem 352 - Lecture 10, Part II Citric Acid Cycle Question for the Day: One of the observations that led Hans Krebs to discover the citric acid cycle, was that dicarboxylic acids, such as fumarate and succinate, had a catalytic effect on the oxidation of glucose to CO2 and H2O by muscle tissue. Explain his observation. Introduction Chem 352, Lecture 10, Part II - Citric Acid Cycle 2 Introduction 13.1 Overview of Pyruvate Oxidation and the Citric Acid Cycle 13.2 Pyruvate Oxidation: A Major Entry Route for Carbon in the Citric Acid Cycle 13.3 The Citric Acid Cycle 13.4 Stoichiometry and Energetics of the Citric Acid Cycle 13.5 Regulation of Pyruvate Dehydrogenase and the Citric Acid Cycle 13.8 Anapleoritic Sequences: The Need to Replace Cycle Intermediates. 13.9 The Glyoxylate Cycle: An Anabolic Variant of the Citric Acid Cycle Chem 352, Lecture 10, Part II - Citric Acid Cycle 2 Introduction Chem 352, Lecture 10, Part II - Citric Acid Cycle 3 Introduction Chem 352, Lecture 10, Part II - Citric Acid Cycle 3 13.1 Overview of Pyruvate Oxidation and the Citric Acid Cycle Overview Chem 352, Lecture 10, Part II - Citric Acid Cycle 5 Overview The citric acid cycle has both catabolic and anabolic functions. • Catabolic - Oxidizes the 2-carbon acetyl group to CO2 and produces reduced nucleotides (NADH + H+ and FADH2) Chem 352, Lecture 10, Part II - Citric Acid Cycle 5 Overview The citric acid cycle has both catabolic and anabolic functions. • Catabolic - Oxidizes the 2-carbon acetyl group to CO2 and produces reduced nucleotides (NADH + H+ and FADH2) • Anabolic - The citric acid cycle intermediates serve as starting material for the biosynthesis of amino acids, heme groups, glucose, et al. -
Is There a Role for Ketoacid Supplements in the Management of CKD? Anuja P
Perspective Is There a Role for Ketoacid Supplements in the Management of CKD? Anuja P. Shah, MD,1 Kamyar Kalantar-Zadeh, MD, PhD,2 and Joel D. Kopple, MD1,3 Ketoacid (KA) analogues of essential amino acids (EAAs) provide several potential advantages for people with advanced chronic kidney disease (CKD). Because KAs lack the amino group bound to the a carbon of an amino acid, they can be converted to their respective amino acids without providing additional nitrogen. It has been well established that a diet with 0.3 to 0.4 g of protein per kilogram per day that is supplemented with KAs and EAAs reduces the generation of potentially toxic metabolic products, as well as the burden of potassium, phosphorus, and possibly sodium, while still providing calcium. These KA/EAA-supplemented very-low-protein diets (VLPDs) can maintain good nutrition, but the appropriate dose of the KA/EAA supplement has not been established. Thus, a KA/EAA dose-response study for good nutrition clearly is needed. Similarly, the composition of the KA/EAA supplement needs to be reexamined; for example, some KA/EAA preparations contain neither the EAA phenylalanine nor its analogue. Indications concerning when to inaugurate a KA/EAA- supplemented VLPD therapy also are unclear. Evidence strongly suggests that these diets can delay the need for maintenance dialysis therapy, but whether they slow the loss of glomerular filtration rate in patients with CKD is less clear, particularly in this era of more vigorous blood pressure control and use of angiotensin/ aldosterone blockade. Some clinicians prescribe KA/EAA supplements for patients with CKD or treated with maintenance dialysis, but with diets that have much higher protein levels than the VLPDs in which these supplements have been studied. -
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 -
Chapter-Vi Protein Metabolism
CHAPTER-VI PROTEIN METABOLISM TRANSAMINATION OF AMINO ACIDS Transaminases catalyze the transfer of -NH2 groups from the amino acids, onto alpha- ketoglutarate. Many different transaminases are known, and they are generally of broad specificity for amino acids (that is, one enzyme can accept as substrates two or more different amino acids). All have the same cofactor requirement - pyridoxal phosphate (vitamin B6). (Two amino acids can be directly deaminated: Serine and Threonine. They do not undergo this process of transamination.) Mechanism of transamination PLP plays a central role here in the interconversion of an amino acid and an alpha-keto acid. (1) Transaminase binds pyridoxal phosphate in a Schiff-base link to a Lysine residue of enzyme (the attachment is to the epsilon-amino group of the Lysine). This forms an "aldimine". (2) As a new substrate substrate enters the active site, its amino group displaces the -NH2 of active site Lysine. Then a new Schiff-base link is formed to the alpha-amino group of the substrate, as the active site Lysine moves aside. (3) There is an electronic rearrangement resulting in shifting the double bond to form a "ketimine". (4) This is followed by hydrolysis to release PMP and an alpha-keto acid. (5) PMP combines with alpha-ketoglutarate in a reversal of steps 1-4. The net result is transfer of an amino group to alpha-ketoglutarate, and release of glutamate, while regenerating the PLP- enzyme complex. DEAMINATION OF AMINO ACIDS Introduction: Deamination is also an oxidative reaction that occurs under aerobic conditions in all tissues but especially the liver. -
Metabolism of Valine and the Exchange of Amino Acids Across the Hind-Limb Muscles of Fed and Starved Sheep
Aust. 1. BioI. Sci., 1986, 39, 379-93 Metabolism of Valine and the Exchange of Amino Acids across the Hind-limb Muscles of Fed and Starved Sheep E. Teleni, A,B E. F. Annison A and D. B. LindsayA,C A Department of Animal Husbandry, University of Sydney, Camden, N.S.W. 2570. B Present address: Graduate School of Tropical Veterinary Science, James Cook University, Townsville, Qld 4811. C Present address: Tropical Cattle Centre, CSIRO, Bruce Highway, North Rockhampton, Qld 4702. Abstract A combination of the isotope-dilution and arterio-venous (A V) difference techniques was used to study simultaneously the metabolism of valine in the whole body and in the hind-limb muscles of fed and starved (40 h) sheep. The net exchange of gluconeogenic amino acids across hind-limb muscles was also studied. Valine entry rate was unaffected by nutritional status. There was significant extraction of valine by hind-limb muscles in both fed and starved sheep. The percentage of valine uptake decarboxylated was higher (P < 0'05) in fed sheep but the amount of valine decarboxylated was not significantly different. The proportion of valine uptake that was transaminated was about 30 times higher in starved sheep. About 54% of valine taken up by hind-limb muscle of starved sheep was metabolized. The corresponding value for fed sheep was 21 %. The contribution of CO2 from valine decarboxylation to total hind-limb muscle C02 output was about 0·2%. The output of alanine in both fed and starved sheep was low but the output of glutamine was relatively high and roughly equivalent to the amounts of aspartate, glutamate and branched-chain amino acids that were catabolized. -
Transaminase Activity in Human Blood
TRANSAMINASE ACTIVITY IN HUMAN BLOOD Arthur Karmen, … , Felix Wróblewski, John S. LaDue J Clin Invest. 1955;34(1):126-133. https://doi.org/10.1172/JCI103055. Research Article Find the latest version: https://jci.me/103055/pdf TRANSAMINASE ACTIVITY IN HUMAN BLOOD By ARTHUR KARMEN, FELIX WROBLEWSKI, AND JOHN S. LADUE (From the Sloan-Kettering Institute, Department of Medicine, Memorial Center, New York City, N. Y.) (Submitted for publication April 3, 1954; accepted July 15, 1954) Enzymatic transamination consists of the en- At the end of the incubation period, proteins were sepa- zyme catalyzed reversible transfer of the alpha rated by adding 7.0 ml. of absolute ethyl alcohol, centri- fuging for ten minutes, and washing the precipitate with amino nitrogen of an amino acid to an alpha-keto 5 ml. of 70 per cent ethanol. The supernatant was evap- acid with the synthesis of a second amino acid and orated to dryness over a water bath and the residue dis- a second alpha-keto acid. Enzymes catalyzing solved in 1.0 ml. of 0.06 M phosphate buffer. Aliquots of different transamination reactions are found widely 0.05 ml. were then applied to Whatman No. 1 filter paper distributed in animal tissues and have been shown and chromatographed by the descending method for 18 hours, using phenol saturated with water as solvent and to change in activity in some tissues during dis- water saturated with phenol to saturate the atmosphere of ease (1-3). These observations prompted the the tank. The papers were then removed and dried in air present study to determine if transaminase ac- at room temperature (5). -
Glial Cells Transform Glucose to Alanine, Which Fuels the Neurons in the Honeybee Retina
The Journal of Neuroscience, March 1994, 14(3): 1339-1351 Glial Cells Transform Glucose to Alanine, which Fuels the Neurons in the Honeybee Retina M. Tsacopoulos,’ A.-L. Veuthey,’ S. G. Saravelos,’ P. Perrottet,’ and G. Tsoupras* ‘Experimental Ophthalmology Laboratory, University of Geneva, School of Medicine, and 2Hewlett-Packard (Switzerland), 1211 Geneva 4, Switzerland The retina of honeybee drone is a nervous tissue with a [Key words: honeybee retina, glial cells, photoreceptor crystal-like structure in which glial cells and photoreceptor neuron, glycogen, glucose fate, pyruvate amination, alanine, neurons constitute two distinct metabolic compartments. The alanine aminotransferase, proline, glutamate] phosphorylation of glucose and its subsequent incorporation into glycogen occur in glia, whereas 0, consumption (CO,) A number of diverse functions have been attributed to glial occurs in the photoreceptors. Experimental evidence showed cells, most of which contribute to the satisfactory functioning that glia phosphorylate glucose and supply the photorecep- of the neurons(for review, seeBarres, 1991). We have provided tors with metabolic substrates. We aimed to identify these evidence supporting the hypothesis that glial cells transform transferred substrates. Using ion-exchange and reversed- metabolic substratesfrom the blood and supply neurons with phase HPLC and gas chromatography-mass spectrometry, metabolites (Tsacopouloset al., 1988). This is a modified ver- we demonstrated that more than 50% of 14C(U)-glucose en- sion of Golgi’s