Survey
* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project
BIOC 460 DR. TISCHLER LECTURE 39 NITROGEN BIOSYNTHETIC PATHWAYS OBJECTIVES 1. Outline the pathways for synthesis of the following nonessential amino acids by identifying the primary source of the carbons and the nitrogen for their synthesis (alan, arg, asp, glu, gln, and tyr) in humans. 1. General role of cofactors-derived from folic acid and how these are important in metabolism of ser, gly, met and cys 1. Discuss significance of S-adenosylmethionine in "onecarbon" metabolism OBJECTIVES (cont.) 4. Identify two specific cofactor forms of vitamin B12 and list the amino acids whose metabolism depends on each form. 5. Concerning heme synthesis: a) describe the reactions involved in the formation of porphobilinogen b) discuss the key features of its regulation c) explain why lead poisoning would affect the oxygen carrying ability of the blood. 6. List the steps in the catabolism of heme to conjugated bilirubin and identify the general condition associated with the accumulation of bilirubin in the body. -ketoglutarate + NH3 NAD(P)H D pyruvate A alanine NH3 + CO2 + ATP + carbamoyl phosphate ADP + Pi NAD(P)+ NH3 + ATP citrulline +aspartate E glutamate glutamate -ketoglutarate ornithine glutamate argininosuccinate glutamine oxaloacetate C aspartate phenylalanine F arginine B tyrosine Figure 1. Synthesis of the nonessential amino acids alanine (A), arginine (B), aspartate (C), glutamate (D), glutamine (E), and tyrosine (F). aspartate asparagine glutamate glutamine 3-phosphoglycerate serine NADH + -ketoglutarate + Pi NAD+ + glutamate + H2O serine THF glycine CH2-THF NH3 + CO2 THF + NAD+ CH2-THF + NADH glycine synthase Figure 2. Synthesis of the nonessential amino acids asparagine, serine, glycine. CH2-THF is methylene tetrahydrofolate Cysteine CH CH33 group donation Cystathionine adenosine S-Adenosylmethionine Homocysteine CH3B12 CH3 THF Methionine synthase ATP Methionine-CH CH3 3 Hydroxy B12 N5-CH CH33 THF Figure 3. Metabolism of CH3-THF, CH3-Cbl, met and cys. Table 1. Summary of the roles of folate and cobalamin in nitrogen metabolism Cofactor Vitamin precursor Methyl-cobalamin Adenosyl-cobalamin Cobalamin (vitamin B12) Methylenetetrahydrofolate Methyltetrahydrofolate Tetrahydrofolate Role methionine metabolism isoleucine/valine metabolism serine/glycine metabolism Folic acid methylcobalamin formation thymidine biosynthesis Succinyl CoA + Glycine -Aminolevulinate synthase pyridoxal phosphate -Aminolevulinic acid -Aminolevulinic acid (two molecules) HEME Fe2+ Protoporphyrin IX Ferrochelatase Pb-sensitive Coproporphyrinogen III MITOCHONDRIA CYTOPLASM Aminolevulinic acid dehydratase zinc-containing enzyme Pb-sensitive Coproporphyrinogen III Uroporphyrinogen III Porphobilinogen 4 molecules Figure 4. Pathway for synthesis of heme combine REGULATION OF HEME SYNTHESIS: Heme: inhibits activity of pre-existing -ALA synthase diminishes transport of -ALA synthase from cytoplasm to mitochondria after its synthesis represses the production of -ALA synthase by regulating gene transcription. TEETH FROM PATIENT WITH PORPHYRIA DISORDER PATIENT WITH PORPHYRIA DISORDER BLOOD CELLS Hemoglobin Stercobilin excreted in feces Globin Heme O2 Heme oxygenase CO Biliverdin IX NADPH Biliverdin reductase NADP+ Bilirubin (waterinsoluble) Urobilin excreted in urine Urobilinogen formed by bacteria KIDNEY reabsorbed INTESTINE into blood via bile duct to intestines Bilirubin diglucuronide (water-soluble) 2 UDP-glucuronic acid Bilirubin LIVER (waterinsoluble) via blood to the liver Figure 5. Catabolism of hemoglobin