Section M Nitrogen Metabolism

1. Section M Nitrogen Metabolism M1. Nitrogen Fixation and Assimilation M2. Amino acid metabolism M3. The urea cycle M4. Hemes and chlorophylls

2. Nitrogen fixation and assimilation 1. The nitrogen cycle 2. Nitrogen fixation 3. Nitrogen assimilation 同化作用

3. The nitrogen cycle The nitrogen cycle is the movement of nitrogen through the food chain from simple inorganic compounds , mainly ammonia, to complex organic compounds.

4. 脱氨作用 分解代谢

5. Nitrogen fixation Nitrogen fixation is the conversion of N2 gas into ammonia, a process carried out by some soil bacteria, cyanobacteria蓝细菌, and the symbiotic 共生的bacteria Rhizobium根瘤菌that invade the root nodules of leguminous豆类plants.

6. Nitrogen fixation This process is carried out by the nitrogenase固氮酶complex, which consists of a reductase and an iron-molybdenum 钼-containing nitrogenase. At least 16ATP molecules are hydrolyzed to form two molecules of ammonia. Leghemoglobin 豆血红蛋白is used to protect the nitrogenase in the Rhizobium from inactivation by O2 .

7. nitrogenase 铁氧还蛋白

8. Nitrogen assimilation Ammonia is assimilated by all organisms into organic nitrogen-containing compounds(amino acids,nucleotides,etc.) by the action of glutamate dehydrogenase (to form glutamate) and glutamine synthetase (to form glutamine).

9. Amino acid family

10. Amino acid degradation • Amino acids are degraded by the removal of the α-amino group and the conversion of the resulting carbon skeleton into one or more metabolic intermediates.

11. Amino acid degradation • Amino acids are termed glucogenic if their carbon skeletons can give rise to the net synthesis of glucose ,and ketogenic of they can give rise to ketone bodies. Some amino acids give rise to more than one intermediate and these lead to the synthesis of glucose as will as ketone bodies. Thus these amino acids are both glucogenic and ketogenic.

12. pathway

13. Transamination • The α-amino group of most amino acids is transferred to α-ketoglutarate to form glutamate and the corresponding α-keto acid • α-amino acid + α-ketoglutarate α-keto acid + glutamate • Enzyme: transaminases

14. Aminotansferase

15. Vitamine B6

16. PLP

17. Oxidative deamination of glutamate

18. glutaminase

19. Amino acid oxidases NH3

20. Metabolism of phenylalanine 四氢生物蝶呤

21. Inborn errors of metabolism • Inherited metabolic disorders 遗传代谢紊乱 • Alkaptonuria 尿黑酸症 • Homogentisate oxidase 尿黑酸氧化酶 • Phenylketonuria 苯丙酮尿 • Phenylalanine hydroxylase 苯丙氨酸羟化酶

22. The urea cycle • Ammonia excretion • The urea cycle • Link to the citric acid cycle • Hyperammonemia • Formation of creatine phosphate • The activated methyl cycle • Uric acid

23. Ammonia excretion • Ammonotelic animal 排氨 ammonia • Uricotelic animal 排尿酸 uric acid • Ureotelic animal 排尿素 urea • terrestrial reptile 陆生爬行动物 • Aquatic animal 水生动物

24. Ammonia excretion • Amminia------ammonotelic organisma—aquatic animals • Uric acid ------uricotelic organisms birds and terrestrial reptiles • Urea-----ureotelic organisms—terrestrial vertebrates

25. The urea cycle • In the urea cycle ammonia is first combined with CO2 to form carbamoyl phosphate. This then combines with ornithine to form citrulline. Citrulline then condenses with aspartate, the source of the second nitrogen atom in urea,to form argininosuccinate. This compound is in turn split to arginine and fumarate, and the arginine then splits to form urea and regenerate ornithine.

26. NH4+ + HCO3- + H2O + 3ATP +aspartate urea + 2ADP + AMP + 2Pi +PPi +fumarate

27. Urea cycle

28. Urea cycle • The reaction place: mitochondria, cytosol • The enzymes are involved in reaction: 1.Carbarroyl phosphate synthetase 氨甲酰磷酸合酶 2.ornithine transcarbamoylae 鸟氨酸转氨甲酰酶 3.argininosuccinate synthetase 精氨琥珀酸合成酶 4.argininosuccinase 精氨琥珀酸酶 5.arginase 精氨酸酶

29. Urea cycle 2

30. Urea cycle 3

31. Urea cycle 4

32. Urea cycle 5

33. Link to the citric acid cycle

34. Oxaloacetate has several possible fates • Transamination to aspartate which can then feed back into the urea cycle; • Condensation with acetyl CoA to form citrate which then continues on round the citric acid cycle ; • Conversion into glucose via gluconeogenesis ; • Conversion into pyruvate

35. Hyperammonemia • A block in any of the urea cycle enzymes leads to an increase in the amount of ammonia in the blood, so-called hyperammonemia

36. ammonia

37. The reason of brain damage in hyperammonemia. 1. Excess ammonia leads to the formation of glutamate and glutamine. 2. It may compromise energy production. 3. It also leads to increase [H+ ]

38. Formation of creatine phosphate • The urea cycle is also the starting point for the synthesis of another important metabolite creatine phosphate. This phosphate provides a reservoir of high-energy phosphate in muscle cells.

39. ATP • As the energy released upon is hydrolysis is greater than that released upon the hydrolysis of ATP (ΔG for creatine phosphate hydrolysis=-10.3kal mol-1 compared with –7.3 kcal mol-1 for ATP hydrolysis ).

40. Creatine phosphate • The first step in the formation of creatine phosphate is the condensation of arginine and glycine to form guanidinoacetate胍基乙酸. Ornithine is released in this reaction and can then be re-utilized by the urea cycle. The guanidinoacetate is then methylated by the methyl group donor S-adenosyl methionine to form creatine, which is in turn phosphory-lated, by creatine kinase to form creatine phosphate.

41. Creatine phosphate

42. The activated methyl cycle • S-Adenosyl methionine serves as donor of methyl groups in numerous biological reactions [e.g.in the for-mation of creatine phosphate and in the synthesis of nucleic acids].It is formed through the action of the activated methyl cycle .

43. The activated methyl cycle • During donation of its Methylgroup to another compound, S-adenosyl methionine is converted into S-adenosyl homocysteine. To regenerate S-adenosyl methionine, the adenosyl group is removed from the S-adenosyl homocysteine to form homo-cysteine高半胱氨酸.

44. The activated methyl cycle • This is then methylated by the enzyme homocysteine methyltransferase, one of only two vitamin B12 containing enzymes found in eukaryotes, to form methionine. The resulting methionine is then activated to S-adenosyl methionine. With the release of all three of the phosphate from ATP.

45. Methyl cycle

46. Uric acid • Uric acid is the main nitrogenous waste product of uricotelic organisms (reptiles, birds and insects), but is also formed in ureotelic organisms from the breakdown of the purine bases from DNA and RNA. • Gout 痛风

47. HEMES AND CHLOROPHYLLS • Tetrapyrrol • 2. Biosynthesis of hemes and chorophylls • 3. Heme degradation

48. Tetrapyrroles • The tetrapyrroles are a family of pigments based on a common chemical structure that includes the hemes and chlorophylls. Hemes are cyclic tetrapyrroles that contain iron and are commonly found as the prosthetic group of hemoglobin, myoglobin and he cytochromes.

49. Heme is as the prosthetic roup Globin 珠蛋白 Protein Heme Cytochomes 细胞色素 Catalases 过氧化氢酶 Enzyme Peroxidase 过氧化物酶

50. chlorophylls • The chlorophylls are modified tetrapyrroles containing magnesium that occur as light-harvesting and reaction center pigments of photosynthesis in plants, algae and photosynthetic bacteria.