Four types of AA d eamination: transamination oxidative deamination

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

4. 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

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

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

7. Summary

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

9. Transmethylation and Met cycle

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

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

12. 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.

13. Formation of bilirubin

14. hydrophobic

16. structure of bilirubin diglucuronide Carbosyl group Hydroxyl group

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

18. 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

20. 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.

21. 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.

22. 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.

23. Element sources of purine bases

24. Element source of pyrimidine

25. Regulation of de novo synthesis of purine nucleotides

26. Summary of purine biosynthesis IMP Deoxyribonucleotide

27. Summary of pyrimidine biosynthesis UMP

28. Catabolism of Purine Nucleotides

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

30. Allopurinol – a suicide inhibitor used to treat Gout

31. 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.

32. Competitive inhibition

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

34. Feed back inhibition

35. 1.1 Purine analogs • 6-Mercaptopurine (6-MP) is a analog of hypoxanthine.

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

37. 1.2 Pyrimidine analogs • 5-fluorouracil (5-FU) is a analog of thymine.

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

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

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

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