lecture22b_11_20_08 - Lecture 22b Overview: • in mammals,...

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Unformatted text preview: Lecture 22b Overview: • in mammals, amino acids are made from intermediates of CAC, glycolysis, and the pentose phosphate pathway Chapter 24: The Biosynthesis of Amino Acids The nitrogen cycle in plants and bacteria The total amount of nitrogen fixed annually in the biosphere exceeds 1011 kg. HW: 24.10, 24.15 Synthesis of 11 nonessential amino acids Overview of amino acid biosynthesis The carbon skeleton precursors derive from three sources: glycolysis (pink), CAC (blue), and the pentose phosphate pathway (purple). Examples: transfer of amino group to !-ketoacid 1) Glycolysis intermediates: 3-phosphoglycerate -> Ser (8) -> Cys (10), Gly (9) pyruvate -> Ala (4) 2) CAC intermediate: oxaloacetate -> Asp (3) -> Asn (5) !-ketoglutarate -> Glu (1) -> Arg (6) , Pro (7), Gln (2) 3) Essential amino acid Phe -> nonessential amino acid Tyr (11) Synthesis of glutamate (1) from CAC intermediates Glutamate dehydrogenase (reductive amination): NH4+ + !-ketoglutarate + NADPH + H+ glutamate + NADP+ + H2O Schiff-base intermediate Synthesis of glutamine (2) from glutamate glutamine synthetase reaction to add 2nd amino group is driven by ATP hydrolysis reduction by NADPH; stereospecific reaction to generate L isomer Synthesis of aspartate (3) and alanine (4) from glutamate, CAC intermediate and glycolysis intermediate Pyridoxal phosphate (PLP)-dependent transaminases catalyze the reactions. From CAC: oxaloacetate + glutamate From glycolysis: pyruvate + glutamate aspartate + !-ketoglutarate General mechanism of PLP-dependent enzymes alanine + !-ketoglutarate Can you draw the mechanisms? Synthesis of asparagine (5) from aspartate analogous to glutamine synthesis, but intermediate is different Synthesis of arginine (6) and proline (7) from glutamate Step one: generation of the semialdehyde intermediate glutamate kinase glutamate dehydrogenase recall this reaction type from the fatty acid degradation pathway (fatty acid activation by fatty acyl-CoA synthetase) reduction of mixed anhydride Synthesis of arginine (6) and proline (7) from glutamate Step two: cyclization (nonenzymatic) and reduction to generate proline, or transamination to generate ornithine (urea cycle intermediate) Arginine formation by urea cycle Generation of arginine from ornithine in the urea cycle pyrroline carboxylate reductase Synthesis of serine (8) from a glycolysis intermediate Three steps: 1) oxidation (phosphoglycerate dehydrogenase), 2) transamination phosphoserine aminotransferase), 3) hydrolysis (phosphoserine phosphatase) Tetrahydrofolate carries activated one-carbon unit Tetrahydrofolate, another important coenzyme, is made of three units (obtained from the diet or from microorganisms in the intestine) see p. 436 Reactions with tetrahydrofolate Synthesis of glycine (9) from serine The coenzyme can exist in three different oxidation states. Glycine synthesis is catalyzed by glycine synthase. Synthesis of SAM Synthesis of glycine (9) from serine Methionine is an essential amino acid used to generate SAM, an important methylating agent. SAM is converted to homocysteine, an important intermediate for cysteine (10) synthesis Regeneration of methionine Generation of cysteine (10) from homocysteine and serine catalyzed by cystathionine !-synthase and cystathionase from glycolysis Shikimate pathway (in bacteria and plants) condensation and deamination; both reactions use the coenzyme PLP from pentose phosphate pathway pathways for aromatic amino acid synthesis Chorismate pathway (in bacteria and plants) Synthesis of tyrosine (11) and phenylalanine from chorismate pathways for aromatic amino acid synthesis ...
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This note was uploaded on 08/04/2010 for the course CHM 6620 taught by Professor Dr.christinechow during the Fall '08 term at Wayne State University.

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