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15 Cards in this Set
- Front
- Back
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What is urea synthesis for?
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Main mechansim for ridding the body of surplus a-amino gps that are made through aa catabolism
-urea cycle detoxifies and catabolizes about 90% of N left over in body) |
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How is the urea cycle compartmentalized?
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-First 2 rxns take place in the mito of the liver (GDH is present in the mito, so this is where oxidative deamination takes place)
-The last 3 rxns take place in the cytoplasm of hepatocytes |
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What is the 1st reaction of the Urea Cycle?
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Carbamoyl Phosphate formation
-Enz: Carbamoyl Phosphate Synthetase 1 (CPS-1) -This is the 3rd NH3 assimilation rxn -This rxn takes place in 3 steps: 1) add P to HCO3-, 2) Add NH3, 3) Add another P -This rxn uses 2 ATP -Product of this reaction: Carbamoyl P, is the precursor of the urea cycle |
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What is NAG?
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Allosteric Activator that is required by CPS-1
-NAG production is proportional to he lvlof aa catabolism -Formed by NAGS from glutamate and acetyl CoA |
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What are the dif btw CPS1 and CPS2?
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CPS1: used for urea synthesis, is in the mito, requires NAG and uses NH4+
CPS2: used for pyridine synthesis, located in the cytoplasm, doesn't need NAG and uses glutamine as NH3 donor |
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What is rxn 2 of the urea cycle?
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Ornithine + Carbamoyl P --> Citrulline
Enz:Ornitihine Transcarbamoylase (OTC) -Takes place in the mito -high E phosphate gp leaves -mutations in OTC are the most common mutations in the urea cycle |
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What is rxn 3 of the urea cycle?
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Citrulline + Aspartate --> Arginosuccinate
Enz: Arginosuccinase Synthetase (ASS) -add 2nd amino gp through aspartate addition -proceeds in 2 step manner 1=> get high E intermediate by combining ATP with citrullin to form citrullyl-AMP 2=> aspartate amino gp attacks the carbonyl to release AMP and water -Mutations in ASS cause hypercitrunillemia |
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What is reaction 4 of the urea cycle?
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Arginossucinate -> Arginine
Enz: Arginosuccinase -Takes place in the cytoplasm -Side prod: fumarate |
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What is reacion 5 of the urea cycle?
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Arginine + H2O -> Urea + Ornithine
Enz: Arginase -Produce ornithine (which will further this cycle) and Urea (which is released into the blood) -Ornithine will be transported to mito for another round -Urea will be transferred from the blood to the urine for excretion |
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How is the glucose-alanine cycle liked to the urea cycle?
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When alanine is transfered to the liver and is transaminated into glutamate and pyruvate, the glutamate is deaminated into a-KGA and NH3
-The NH3 is then combined with HCO3 to form Carbamoyl Phosphate, through the addition of 2 ATPs |
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Where do the amino groups in urea come from?
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Both the amino groups come from glutamate (aspartate is produced from glutamate by transamination of OAA. Aspartate is regenerated from Fumarate in the Urea cycle. Fumarate forms malate which forms OAA (all part of CAC) which is transaminated via glutamate to produce aspartate. Transaminases can accept a-amino gps and OAA, but OAA accepted at a lower level, which shows how aspartate can be formed)
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What is the E cost of the Urea cycle?
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-incorporation of each a-amino group uses 2 ATP
=> This E can be regenerated through: Gluconeogenesis and oxidative P through NADH and NADPH |
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How is the Urea cycle regulated in the short term?
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-GDH is regulated by the E charge of teh cell (a lot of GTP, enzyme will be less active)
-CPS-1 requires NAG and NAG can be regulated by its substrates (Glutamate and Arginine) |
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How is the urea cycle regulated in the long term?
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-Transcription of all 5 urea cycle enz can be induced
-NAG transcription can be induced -inc transcription after aa loading -Transcripton decrease when there is less protein in the diet -Enz are co-induced (.: they'll all inc or dec tog) -Transient increase in urea cycle enz in the early stages of starvation |
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U?rea cycle disorders.
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-All mutations in the Urea cycle lead to hyperammonemia
-Mutations in CPS-1 and OTC are the worst -High ammonia lvls damages the brain and nervous system =>Treatment: -Feed benzoate and phenylacetate => products of these rxn can be easily secreted by the kidneys. Can rid body of glycine => phenylacetate can get rid of 2 aa gps at once. Can rid the body of phenylacetate and glutamine -Drug: Ammonul => stabilizes patients with urea cycle mutations -Only long term solution: Gene therapy (Could also use RNAi) |
