Chap_22_2010_v2

Chap_22_2010_v2 - Chemical Aspects of Biological Systems...

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Unformatted text preview: Chemical Aspects of Biological Systems Information Pathways (142C/242C) Meetin g Time: Ins tru ctor: TR, 12: 30- 1:4 5 P M, Phelps H all 3 515 Prof. L u c J aeger Co ntact: jaeg er@ chem. ucsb.edu Office: P S BN 464 9A Office Hrs: R , 2 :00 -3:00 PM; by ap pointm ent wade (wg rabow@ chem.ucs b.e du) PSBN 46 38, P hone 5 302 TR (W ad e) : 1 1:00 AM-12:00 AM an d by a ppointment TA: TA Office Hours : http://www.chem.ucsb.edu/coursepages/index.shtml Username: chem_142c and Password: chem_242c Part 1: overview of nitrogen metabolism A. Fixation of nitrogen (by the nitrogenase complex) B. Incorporation of NH3/ NH4+ through glutamate and glutamine C. Glutamine synthetase: the primary regulatory point in nitrogen metabolism D.The several classes of reactions that play fundamental roles in the biosynthesis of amino acids and nucleotides (1) Transamination reactions and other rearrangements promoted by enzymes containing pyridoxal phosphate (PLP) (2) Transfer of one-carbon groups using tetrahydrofolate (H 4 folate ) or Sadenosylmethionine (Ado-Met) as cofactors (3) Transfer of amino groups derived from the amide nitrogen of Gln Part 2: brief overview of amino-acid catabolism in mammals 1 Part 2: Brief overview of amino-acid catabolism in mammals Chap.22 Aas can be a significant source of energy! This varies depending the type of organism and metabolic conditions. The amino groups and the carbon skeleton take separate but interconnected pathways! Because only few organisms can produce NH3 from N2, amino groups are carefully husbanded in biological systems. Chap.18 Chap.16 Chap.14 A. Metabolic fates of amino-acids 1. Enzymatic degradation of dietary proteins • • Pepsin cuts protein into peptides in the stomach. Trypsin and chymotrypsin cut proteins and larger peptides into smaller peptides in the small intestine. Aminopeptidase and carboxypeptidases A and B degrade peptides into amino acids in the small intestine. • 2 2. Amino group catabolism (overview from vertebrate liver) Most of the ammonia formed in vertebrates is transported as Glu, Gln or Alanine . Ammonia is eliminated as ammonia, urea (Chap. 18) or/and uric acid (Chap.22) Aminotransferase PLP Glu dehydrogenase Glutaminase In human and great apes, excess of nitrogen is eliminated as urea (from aas ) and uric acid (from purines ) 3. The glucose-alanine cycle •Vigorously working muscles operate nearly anaerobically and rely on glycolysis for energy •Glycolysis yields pyruvate that muscles cannot metabolize aerobically; if not eliminated lactic acid will build up •This pyruvate can be converted to alanine for transport into liver. •The pyruvate produced by deamination of Ala in the liver is converted to glucose and transported back to the muscle. 3 B. The urea cycle and related reactions In mammals Aminotransferase NADP B. The urea cycle and related reactions aa oxaloacetate Aminotransferase α -keto acid keto acid Aspartate aa Ornithine transcarbamoylase α-ketoglutarate Aminotransferase α -keto acid keto acid glutamate Argininosuccinate Argininosuccinate synthase synthase Malate Arginase Arginine fumarase One of the amino group of urea comes from Carbamoyl phosphate, the other comes from Aspartate Malate dehydrogenase 4 The Aspartate-argininosuccinate shunt The urea cycle results in a net conversion of oxaloacetate to fumarate , both intermediates of the citirc acid cycle. Urea cycle and citric acid cycle are connected! “Krebs bicycle ” Catabolism of purine nucleotides Primates excrete much more nitrogen as urea via the urea cycle (Chapter 18) than as uric acid from purine degradation. Fish excrete much more nitrogen as NH 4+ than as urea produced by the pathway shown here. 5 Part 3: biosynthesis of amino acids A. B. C. D. E. F. α-ketoglutarate amino acids family 3-Phosphoglycerate amino acids family Oxaloacetate and Pyruvate amino acids families Aromatic amino acids family Histidine family Molecules derived from amino acids Part 3: biosynthesis of amino acids Most bacteria and plants are able to synthesize the 20 amino acids. Mammals can synthesized only half of them. Amino acids that are not needed in the diet are nonessential aas whereas those that are needed are called essential aas. 6 All aas are derived from intermediates in glycolysis, the citric acid cycle or the pentose phosphate pathway. Glu and Gln are the main source of nitrogen. Overview of aa synthesis (Chapter 22) aa Glucogenic and ketogenic Summary of aa catabolism (Chapter 18) 7 Amino acid biosynthetic families grouped by metabolic precursor + H Important amino acid precursors to remember Phosphoenolpyruvate α- ketoglutarate 3- phosphoglycerate Pyruvate Oxaloacetate H Erythrose 4-phosphate Ribose-5 phosphate In addition to all these precursors, an important intermediate is PRPP: Ribose-5 phosphate + ATP PRPP + AMP ribose phosphate pyrophosphokinase (allosteric enzyme regulated by biomolecules for which PRPP is a precursor) 8 A. α-ketoglutarate amino acids family 1 step 1 step 3 steps 8 steps Essential aa Reminder from last lecture! Formation of Glutamine from glutamate by glutamine synthetase (found in all organisms) Glutamate + NH4+ + ATP glutamine + ADP + Pi + H+ 9 Reminder from last lecture! Second reaction is catalyzed by glutamate synthetase (found in bacteria and plants) α-Ketoglutarate + glutamine + NADPH + H+ The net reaction with the previous one is: α-Ketoglutarate + NADPH + NH4++ ATP L-glutamate +NADP+ + ADP + Pi 2 glutamate + NADP+ In animals, there is no glutamate synthase Thus to maintain a high level of glutamate -> Transamination mechanism Formation of Pro In mammals Amino transferase 1. Kinase 2. Deshydrogenase Nonenzymatic Reductase 5 C are from glutamate. Pro is a cyclized derivative of Glu 10 Proline 5 6 Like in urea cycle Works in both directions 7 urea Arginase 8 H2O In mammals, Pro can be synthetized from Arg. If deficiency in Arg then GγSA can be converted to Orn (See Chap 18) Eight steps are necessary to form Arg in bacteria (de novo synthesis of ornithine ) 1 The α-amino group of Glu is acetylated to avoid cyclization 2 The acetyl group is removed after transamination Urea cycle 5 H2O 3 4 Ornithine CH3COON- acetylornithinase 11 Urea cycle and related reactions aa oxaloacetate Aminotransferase α -keto acid keto acid Aspartate aa Ornithine transcarbamoylase α-ketoglutarate Aminotransferase α -keto acid keto acid glutamate Argininosuccinate Argininosuccinate synthase synthase Malate Arginase Arginine fumarase One of the amino group of urea comes from Carbamoyl phosphate, the other comes from Aspartate Malate dehydrogenase B.3-Phosphoglycerate amino acids family 4 steps 1 step 2 steps Non-essential aas 12 This pathway is universal among organisms Formation of Gly from Ser 13 Reminder from last lecture! Transfer of one-carbon groups using tetrahydrofolate Biosynthesis of Cys from Ser in bacteria and plants 14 Bacteria and plants produce the reduced sulfur from environmental sulfates Biosynthesis of Cys from serine and homocystein in mammals Reminder from last lecture! Transfer of one-carbon groups using S-Adenosyl -methionine 15 Biosynthesis of Cys from serine and homocystein in mammals 16 ...
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This note was uploaded on 04/25/2010 for the course CHEM 142c taught by Professor Reich,n during the Spring '08 term at UCSB.

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