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44 Cards in this Set
- Front
- Back
Where does the urea cycle take place? |
The liver |
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Liver damage can lead to ________ |
toxic hyperammonemia |
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What structure does hyperammonemia have the most severe effect on? |
the brain |
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What is the purpose of the urea cycle? |
To detoxify ammonia and form urea. Urea contains two N's that can be released via the kidney into the urine |
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Where in the cell does the urea cycle take place? |
mitochondria and cytosol |
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Urea cycle regulation |
Enzyme induction after a meal or during starvation. Regulated enzyme: carbamoyl-P synthetase I which needs N-acetyle glutamate as an absolute activator. Arginine and glutamate are the main players in the activation of the cycle |
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What is the regulated enzyme in the urea cycle? |
carbamoyl-P synthetase I |
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What is the absolute activator of carbamoyl-P synthetase I? |
N-acetyl-glutamate |
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Most tissues release which two amino acids into the blood? |
alanine and glutamine |
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How is alanine formed? |
Transamination of pyruvate that is generated in glycolysis |
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What are the advantages of glutamine? |
It transports two nitrogens in its structure and the synthesis of glutamine can be used to trap free ammonia into a harmless molecule (glutamine synthetase has a low Km, high affinity for free ammonia) |
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What is needed for the formation of urea? |
free ammonia and aspartate in a 1:1 ratio. The carbon and oxygen are derived from carbon dioxide |
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Uptake and deamination of what amino acid(s) generates free ammonia? |
glutamine and glutamate |
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In most tissues, free ammonia is detoxified by what enzyme? |
glutamine synthetase |
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After uptake of glutamine into the liver, what enzyme releases free ammonia? |
glutaminase |
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The glutamate formed from the reaction of glutaminase can also be used to generate more ammonia using what enzyme? |
glutamate dehydrogenase |
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Glutamate can also be used to form which amino acid for the urea cycle? |
aspartate |
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What is the glucose-alanine cycle? |
Describes a cycle between liver and muscle. Liver releases glucose which can be used in muscle for glycolysis. Pyruvate can be transaminated to alanine using glutamate that was formed during the degradation of amino acids. Alanine is released from muscle into the blood and taken up by the liver. The carbon of alanine can be used after transamination for gluconeogenesis and the nitrogen is used for urea synthesis. |
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What amino acid can be the product or the substrate in transamination? |
glutamate |
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Oxidative deamination of ___________ catalyzed by glutamate dehydrogenase forms free ammonia and alpha keto glutarate. |
glutamate |
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Oxidative deamination of glutamate by _____________ forms what? |
glutamate dehydrogenase, free ammonia and alpha ketoglutarate |
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Enzyme induction can take place after what? |
high protein diet or during starvation. Otherwise the urea cycle is mainly regulated via availability of substrates |
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What is the urea cycle mainly regulated by? |
availability of substrates |
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High arginine levels stimulate __________ which forms urea and ornithine which enters liver mitochondria to continue the cyle |
arginase |
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In the urea cycle, _________ enters the mitochondria |
L-ornithine |
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High arginine levels in addition to high glutamate levels stimulate formation of _____________ which is the absolute necessary activator for ______________. |
N-acetyl-glutamate, carbamoyl-P synthetase I |
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Glutamate has a central role in providing both ___________ (by transamination only using glutamate) and ____________ (which can also be provided by other amino acids) |
aspartate, free ammonia |
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What is released in the urea cycle? |
fumarate |
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The released fumarate can be used in liver cytosol to generate ___________ that is needed for the next round of the urea cycle |
aspartate |
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What is hyperammonemia? |
blood ammonia levels above 1000 micromol/L, normal levels are 5 to 50 |
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What does ammonia intoxication include? |
tremors, slurring of speech, somnolence, vomiting, cerebral edema, and blurring vision |
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What enzymes deplete the brain of glutamate and GABA? |
glutamate dehydrogenase and glutamine synthetase |
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High glutamine levels in brain cells leads to what? |
cerebral edema |
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Glutamate and GABA are what? |
neurotransmitters |
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High concentration of ammonia in blood can cause what? |
lethargy, convulsions, coma and death |
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Ammonia is also formed by intestinal bacteria using what enzyme? |
urease |
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Some urea reaches the intestines, and the formed ammonia gets back into the liver via what? |
portal circulation |
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If the liver cannot trap ammonia with ____________, then hyperammonemia can occur |
glutamate degydrogenase |
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What can indicate a defect in the urea cycle? |
A combination of hyperammonemia, decreased blood urea nitrogen (BUN), and increased blood glutamine levels |
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What is ornithine transcarbamoylase deficiency? |
X-linked genetic defect. Leads to high levels of carbamoyl-phosphate, which can leave into the cytosol. There it leads to uncontrolled, highly increased pyriidine synthesis that overwhelms the enzymes and the resulting high levels of orotic acid lead to orotic aciduria |
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What symptoms do patients with ornithine transcarbaoylase deficiency (OTC deficiency) have? |
- Hyperammonemia |
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What is the treatment for hyperammonemia? |
- Low protein diet |
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What does benzoic acid do? |
Binds glycine and forms hippuric acid that is excreted in the urine |
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What does phenylbutyrate do? |
Converted to phenylacetate (bad odor) inside the body. Phenylacetate then binds glutamine and phenylacetylglutamine and is excreted in the urine |