Lecture 15 Slides rh

AMINO ACID CATABOLISM

fate of amino nitrogen in mammals fig 18-1

metabolism of amino nitrogen in liver fig 18-2

nitrogen removal molecules… fig 18-2

metabolism of amino nitrogen in liver fig 18-2

transamination reaction pg 677

fig 18-5

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

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

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

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

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

metabolism of amino nitrogen in liver fig 18-2

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

metabolism of amino nitrogen in liver fig 18-2

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

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

fig 18-10

fig 18-10

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

making a transferable carbamoyl group… fig 18-11

transferring that carbamoyl group…

transfering that carbamoyl group… ornithine citruline

adding a good leaving group… citruline ATP

using that good leaving group to do chemistry…

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

production of arginine… + fumarate

liberation of urea… arginine H2O urea!! ornithine

we must consume amino acids…

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

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

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

glycine porphyrins glycine creatine arginine things from amino acids… stop

things from amino acids… glutathione! fig 22-27

diseases of amino acid catabolism fig 18-23

an example: pheylketonurea or PKU fig 18-23

an example: pheylketonurea or PKU aspartame fig 18-23

AMINO ACID ANABOLISM

it’s a legume! fixes nitrogen

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.

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

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

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

allosteric regulation of glutamine synthetase fig 22-6

glutamine amidotransferases gln S NH3+ S S NH3+

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

classic allosteric regulation of amino acid synthesis fig 22-21

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

Lecture 16 Slides rh

Nucleotide Metabolism

nucleotide nucleoside

a key molecule in purine and pyrimidine biosynthesis

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

fig 22-33

fig 22-33

ETC. fig 22-33, sorta

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

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

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

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

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

fig 22-38

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

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

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…

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

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

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

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

more chemotherapeutics

inhibitors of dihydrofolate reductase cycle fig 22-49

catabolism of purines… xanthine oxidase fig 22-45

fig 22-45

out with gout!!! 1735

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

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