Urea Cycle

Front 1

Draw pathway

Back 1

Draw pathway

Front 2

what the purpose of the urea cycle

Back 2

NH4+ is neurotoxic (CNS)
thus it is converted to urea in the liver via urea cycle thn excreted in the urine

Front 3

production of NH4

Back 3

alanine --> pyruvate in the liver produces urea

Front 4

normal range of ammonia

Back 4

calculated via BUN value
30-60

Front 5

enzymes that cause hyperammonemia

Back 5

1,2,3,4,5
this causes metabolites before them to accumulate
and the defect in the first three causes accumulation of ammonia

Front 6

effect of brain damage

Back 6

cannot make urea
cannot eliminate urea

Front 7

why is it neurotoxic

Back 7

#1 Blood pH
#2 Energy
#3 Neurotransmitter
#4 Cerebral edema

Front 8

Brain toxicity #1

Back 8

decreases pH increasing aciditiy of the blood causing acidosis

Front 9

Blood Toxicity #2

Back 9

transverses blood-brain barrier
NH4 + alpha ketoglutatarate -> glutamate via GDH
depletes alpha ketoglutarate
which decrease the amount OAA produced
via TCA cycle (which is decreased)
BRAIN DEATH

Front 10

Blood Toxicity #3

Back 10

Neurotransmitter
increased glutamate (via glutamate DH)
increased glutamine (via glutamine synthetase)
conversion depletes glutamate
depleted glutamate
depletes neurotransmitter
glutamate, GABA

Front 11

Neurotoxicity #4

Back 11

Cerebral Edema
increased glutamine (coverted from glutamate)
glial cells controlled by organic osmyltic concentration
which is glutamine
results in cerebral edema seen in infants with hyperammonemia
incrased glutamine, increased gglial cell

Front 12

organic osmyltic

Back 12

which is glutamine
effects astrocytes (glial cells)

Front 13

Treatment of hyperammonemia

Back 13

#1 Restricting dietary proteins
#2 Mixtures keto acids
#4 Acidification of urnine
#5 addition of arginine
#3 benzoate/ phenylacetetate

Front 14

Treatment of hyperammonemia #1

Back 14

restrict dietary proteins because the bacteria ureases in the gut release ammonia from the amino acids
thus also use antibiotics to kill these bacteria

Front 15

Treatment of hyperammonemia #2

Back 15

giving keto acids instead of their alpha amino acid derivatives reduces the amino acid catabolism process

Front 16

Treatment of hyperammonemia #3

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acidification of the urine
makes ammonia difusse through the tissue and be soluble
and thus be released via urine

Front 17

charge of ammonia

Back 17

depends on the pH
charged (NH4+) nondifusible
uncharged (NH3) diffusible, thus reabsorbed of portal vein into liver

Front 18

Treatment of hyperammonemia #4

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gives benzoate/phenylacteate to provide an alternate pathway for ammonia excretion

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Treatment of hyperammonemia #5

Back 19

addition of arginine

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Urea cycle 1

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Citruline to arginosuccinate
addition of aspartate
arginosuccinate synthetase
ATP-->AMP + Pi

Front 21

Urea cycle 2

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Arginosuccinate to arginine
fumurate leaves
arginosuccinate lyase

Front 22

Urea cycle 3

Back 22

arginine to orthinine
arginase
H20 --> urea
only located in the liver

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Urea cycle 4

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orthinine transcarbomylase
Orthinine to citruline
couples carbomylphosphate --> pi
transfers carbamoyl (NH2-C=O)
release pi

Front 24

Urea cycle 5

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NH4+ + CO2 --> carbamoyl phosphate
carbamoyl synthetase I
2 ATP-->2 ADP + Pi
NH4 --> NH4
HCO3--> HCO3
rate limiting step

Front 25

what is the rete limiting step in the urea cycle

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step #5

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location of the urea cycle

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cytosol : 1,2,3
mitochondria: 4,5

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Regulation of urea cycle occurs at what step

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step 5

Front 28

Regulation of urea cycle

Back 28

#1 N-acetylglutamate
#2 argininine
#3 long term

Front 29

Regulation of urea cycle #1

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N-actylglutamate is activator of CPT I
increase after a meal
dependent on acetylglutamate which is in excess after a protein rich meal

Front 30

Steady state concentration of N-acylglutamate

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set by acetyl coa and glutamate which make it

Front 31

production of N-acylglutamate

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Acetyl coa + glutamate --> N acylglutamate
via N-acylglutamate synthetase

Front 32

Regulation of urea cycle #2

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arginine is a postibve allosteric activor of N-acylglutamate synthetase

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Regulation of urea cycle #3

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excess protein intake leads to elevated NH4
which leads to the increased expression of urea cycle enzymes
occurs during starvation when muscle proteins are metabolized to produce energy
when they are metabolized they produce NH4+

Front 34

clinical manefestation of Gout

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hyperuricemia
MSU (monosodium urate)
CPPD (calcium pyrophosphate dihydrate) crystals
in the synovial fluid of the joints
leads to inflammation and gouty arthirits