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Lecture 15 Slides rh.

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1 Lecture 15 Slides rh

2 AMINO ACID CATABOLISM

3 fate of amino nitrogen in mammals
fig 18-1

4 metabolism of amino nitrogen in liver
fig 18-2

5 nitrogen removal molecules…
fig 18-2

6 metabolism of amino nitrogen in liver
fig 18-2

7 transamination reaction
pg 677

8 fig 18-5

9 chemistry of the PLP aldehyde: Schiff base formation fig 18-5

10 PLP reactions: decarboxylation, deamination, racemazation
fig 18-6

11 PLP reactions: the transamination two-step...
fig 18-6

12 oxidative deamination: from amino group to ammonia
fig 18-7

13 oxidative deamination: from amino group to ammonia
genetic disorder from loss of GTP allosteric control… fig 18-7 NOT

14 metabolism of amino nitrogen in liver
fig 18-2

15 glutamine as a carrier of NH3 from tissue to liver fig 18-8

16 metabolism of amino nitrogen in liver
fig 18-2

17 shuttling of NH4+ from muscle to liver reminiscent of the Cori cycle, yes? actual fig 18-9

18 the urea cycle as a method of safely disposing of all that NH3+ fig 18-19

19 fig 18-10

20 fig 18-10

21 logic of the urea cycle: NH4+, aspartate, and CO2

22 making a transferable carbamoyl group…
fig 18-11

23 transferring that carbamoyl group…

24 transfering that carbamoyl group…
ornithine citruline

25 adding a good leaving group…
citruline ATP

26 using that good leaving group to do chemistry…

27 using that good leaving group to do chemistry…
fig 18-11

28 production of arginine…
+ fumarate

29 liberation of urea… arginine H2O urea!! ornithine

30 we must consume amino acids…

31 catabolism of amino acids: (most) roads lead to the Krebs cycle
fig 18-15

32 amino acids are used to make many things fig 18-22

33 epinephrine norepinephrine dopamine tyrosine gaminobuterate
things from amino acids… epinephrine norepinephrine dopamine tyrosine gaminobuterate (glutamate) glutamate tryptophan serotonin arginine NO neurotransmitters!

34 glycine porphyrins glycine creatine arginine things from amino acids…
stop

35 things from amino acids… glutathione! fig 22-27

36 diseases of amino acid catabolism fig 18-23

37 an example: pheylketonurea or PKU fig 18-23

38 an example: pheylketonurea or PKU aspartame fig 18-23

39

40 AMINO ACID ANABOLISM

41 it’s a legume! fixes nitrogen

42 N2 NH4+ NOx NH4+ in a.a. conversion to needed compounds
Usual route of N from atmosphere to mammalian metabolism N2 nitrogen fixation nitrifying bacteria NH4+ NOx plants, some bacteria conversion to needed compounds mammalian diet NH4+ in a.a.

43 nitrogenase at the heart of N2 fixation very sensitive to O2!!!!!
fig 22-2

44 symbiosis of N2 fixing bacteria
a protected environment: leghemoglobin fig 22-4

45 glutamine synthetase glutamate + ATP + NH4+ glutamine + ADP + Pi
fig 22-5

46 allosteric regulation of glutamine synthetase fig 22-6

47 glutamine amidotransferases
gln S NH3+ S S NH3+

48 amino acids are synthesize from Krebs, glycolysis and pentose
phosphate pathways Table 22-01

49 classic allosteric regulation of amino acid synthesis
fig 22-21

50 interlocking regulation of multiple pathways by allosteric regulation
fig 22-22

51

52 Lecture 16 Slides rh

53 Nucleotide Metabolism

54 nucleotide nucleoside

55

56

57 a key molecule in purine and pyrimidine biosynthesis

58 purines: where does all them darn atoms come from??
fig 22-32

59 fig 22-33

60 fig 22-33

61 ETC. fig 22-33, sorta

62 inosine, built “on the ribose” to make IMP fig 22-33, still

63 and inosinate begat adenylate and xanthylate, and xanthylate
begat guanylate… fig 22-34

64 regulation of the early steps of purine synthesis fig 22-35

65 pyrimidine biosynthesis orotate, built “off the ribose” fig 22-36

66 pyrimidine biosynthesis OTP then modified to CTP, etc fig 22-36

67 fig 22-38

68 1) de novo synthesis (see above)
Two ways for mammals to make and/or use purines and pyrimidines 1) de novo synthesis (see above) 2) salvage pathways Ad + PRPP AMP + PP

69 1) de novo synthesis (see above)
Two ways for mammals to make and/or use purines and pyrimidines 1) de novo synthesis (see above) 2) salvage pathways hypoxanthine + PRPP IMP + PP Lesch-Nyhan disease

70 1) de novo synthesis (see above)
Two ways for mammals to make and/or use purines and pyrimidines 1) de novo synthesis (see above) 2) salvage pathways pyrimidine salvage is similar but not well understood in mammals…

71 inhibitors of glutamine amindo- transferases chemo- therapeutics fig 22-48

72 remember the “D” in DNA??? either or fig 22-39

73 what’s the difference between T and U?? fig 22-44

74 where the THF gets its methy... fig 22-44

75 more chemotherapeutics

76 inhibitors of dihydrofolate reductase cycle
fig 22-49

77 catabolism of purines… xanthine oxidase fig 22-45

78 fig 22-45

79 out with gout!!! 1735

80 out with gout!!! xanthine oxidase too active fig 22-47

81 out with gout!!! xanthine oxidase inhibitor fig 22-47


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