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Four types of AA d eamination: transamination oxidative deamination

Four types of AA d eamination: transamination oxidative deamination union deamination non-oxidative deamination. 1. Sources: ⑴ Endogenous sources: ① Deamination of AAs --main source ② O ther nitrogen containing compounds

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Four types of AA d eamination: transamination oxidative deamination

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  1. Four types of AA deamination: transamination oxidative deamination union deamination non-oxidative deamination

  2. 1. Sources: ⑴ Endogenous sources: ①Deamination of AAs--main source ② Other nitrogen containing compounds ③ Kidney secretion (Gln) NH3+H+ NH4 Source and outlet of NH3

  3. ⑵ Exogenous sources: ① Putrefaction in the intestine. ② Degradation of urea in the intestine NH3+H+ NH4

  4. 2. Outlets: (1) Formation of urea (2) Formation of Gln (3) Excrete in urine (4) Synthesis of AA

  5. Summary

  6. One carbon unit One carbon units are carried by FH4

  7. Transmethylation and Met cycle

  8. PBG Heme ALA dehydratase ALA synthase ferrochelatase Gly succinyl CoA Linear tetrapyrrol Protoporphyrin Ⅸ Protoporphyrinogen Ⅸ CPGⅢ UPGⅢ

  9. ①ALA synthase ② decarboxylase ③ transaminase coenzyme -pyridoxal phosphate

  10. 1. Formation and transport of bilirubin • *The source of bilirubin • The compounds involving iron prophyrin in the body are hemoglobin, myoglobin, cytochrome, peroxidase, and catalase, etc.

  11. Formation of bilirubin

  12. hydrophobic

  13. structure of bilirubin diglucuronide Carbosyl group Hydroxyl group

  14. Jaundice • Hemolytic (prehepatic) jaundice • Hepatocellular (hepatic) jaundice • Obstructive (posthepatic) jaundice

  15. Laboratory results in patients with jaundice Hemolytic jaundice Hepatocellular jaundice Obstructive jaundice normal Serum bilirubin < > > > 1 mg/dl 1 mg/dl 1 mg/dl 1 mg/dl total ↑↑ ↑ direct 0~ 0.8mg/dl ↑↑ ↑ < 1 indirect Urine bile pigments – – + + + + urobilirubin ↑ ↓ urobilinogen A few uncertainty ↑ ↓ urobilin A few uncertainty Clay color Simple or normal Color of feces normal dark

  16. two pathways of nucleotides De novo synthesis: precursors: amino acids, ribose-5-phosphate, CO2, and one-carbon units. Salvage pathways: recycle the free bases or nucleosides.

  17. PurineDe novo synthesis a. Purines are synthesized using 5-phosphoribose as the starting material step by step. b. PRPP is active donor of R-5-P. c. AMP and GMP are synthesized further at the base of IMP.

  18. Pyrimidine De novo synthesis • The pyrimidine ring is first synthesized, then combines with PRPP. • UMP is first synthesized, then UMP is used for synthesizing other pyrimidine nucleotides.

  19. Element sources of purine bases

  20. Element source of pyrimidine

  21. Regulation of de novo synthesis of purine nucleotides

  22. Summary of purine biosynthesis IMP Deoxyribonucleotide

  23. Summary of pyrimidine biosynthesis UMP

  24. Catabolism of Purine Nucleotides

  25. Elevated concentration of uric acidcausegout. • Crystals of sodium uratedeposited in the joints and the kidney tubules.

  26. Allopurinol – a suicide inhibitor used to treat Gout

  27. Antimetabolites ofnucleotides • structural analogs of purine, amino acids and folic acid. They can interfere, inhibit or block synthesis pathway of purine nucleotides and further block synthesis of RNA, DNA, and proteins.

  28. Competitive inhibition

  29. inhibitor • structural similarities with substrates. • compete for the active sites with S.

  30. Feed back inhibition

  31. 1.1 Purine analogs • 6-Mercaptopurine (6-MP) is a analog of hypoxanthine.

  32. - - - - - de novo synthesis • 6-MP nucleotide is a analog of IMP amidotransferase IMP 6-MP 6-MP nucleotide AMP and GMP HGPRT salvage pathway

  33. 1.2 Pyrimidine analogs • 5-fluorouracil (5-FU) is a analog of thymine.

  34. dTMP dUMP 5-FdUMP 5-FU 5-FUTP Synthesis of RNA Destroy structure of RNA

  35. 2. Amino acid analogs • Azaserine (AS) is a analog of Gln.

  36. 3. Folic acid analogs • Aminopterin(AP)andMethotrexate (MTX)

  37. 4. Nucleoside analogs • Arabinosyl cytosine (ara-c) inhibits the synthesis of dCDP.

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