Term
| What part of the body is building up ammonia particularly toxic to? |
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Definition
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Term
| Explain the location of amino acid metabolic enzymes and how they can be used as a diagnostic tool |
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Definition
1. They are located INSIDE of cells (mostly in the liver, called aminotransferases)
2. Their presence in blood and serum can be used as a diagnostic tool to detect tissue damage |
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Term
| What is the bodies only sources of amino acids |
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Definition
Nutrition and synthesis
The are NEVER stored. They are degraded if they are not used. |
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Term
| Explain the processing of proteins from the diet |
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Definition
1. Stomach acids denature proteins
2. Pepsin cleaves them into shorter peptides
3. Pancreas and small intestine futher degrade them
4. Absorbed and processed by the liver through the portal vein |
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Term
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Definition
| Malabsorption of amino acids due to immune mediated damage to the small intesting by gluten |
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Term
| How are amino acid concentration gradients maintained in cells? |
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Definition
ATP dependent active transport
Note: There are multiple transporters for amino acids (at least 7) with overlapping specificities |
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Term
| What is the most commonly occurring genetic error of amino acid transport and what does it affect? |
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Definition
1. Cystinuria, an autosomal recessive disorder
2. Affects the uptake of cystine (defect in the uptake mechanism) |
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Term
| What is the amino acid pool and what is nitrogen balance? |
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Definition
1. amino acid pool is the available amino acids for anabolism (make flucose, fatty acids, ketone bodies, creatine, neurotransmitters, etc.) based on protein degradation and dietary protein
2. Nitrogen balance is the input of balance minus the output of it. They should be equal to maintain homeostasis. |
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Term
| What are the major breakdown products of the urea cycle and how are they excreted? |
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Definition
| Ammonium goes into the urea cycle and the major outputs are urea and ammonia, which are excreted primarily in urine |
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Term
| What is the major source of nitrogen in the blood vs. that in urine? |
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Definition
Blood: Non protein nitrogen
Urine: Urea (90% of nitrogen is in this form here)
Note: The concentraion of nitrogen in these locations is a relatively small percentage of their overall makeup, but these percentages are fairly study and fluctuations in them are indicative of disease |
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Term
| What types of problems will lead to an increase in blood urea? |
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Definition
Kidney problems
High protein intake
Other random diseases that only gunners should memorize |
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Term
| What conditions will cause a decrease in blood urea content? |
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Definition
Liver dysfunction
Low protein intake
Infections
Malabsorption of amino acids (i.e. celiac disease) |
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Term
| How are blood ammonia levels maintained and why is it essential they not fluctuate? |
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Definition
Glutamate in tandem with the liver serve to maintain levels of blood ammonia
It is extremely toxic to CNS and brain tissue, so it must be kept low |
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Term
| Describe the shuttle system that helps to remove ammonia from the CNS |
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Definition
1. alpha keto glutarate takes up an ammonia to form glutamate, an neurotransmitter
2. As levels of glutamate get high in the CNS, it can react to take up another ammonia to form glutamine (ATP required)
3. Glutamine goes to kidney
4. Glutamine reacts with glutaminase (hydrolysis reaction) to release one of the ammonias in the kidney for excretion, glutamate is reformed
5. Glutamate goes to the liver
6. Glutamate is converted to alpha ketoglutarate (cofactor is NAD) to release 2nd ammonia for excretion
Note: As for the glutamate - alpha ketoglutarate reaction, in the brain the formation of glutamate is favored to bind ammonia, in the liver the reverse if favored to release it for excretion |
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Term
| Describe the regulation of the alpha ketoglutarate - glutamate reaction system and how it allows favoritism towards a specific direction |
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Definition
1. Different cofactors (NADPH alllows glutamate synthesis, NAD+ allows alpha ketoglutarate synthesis)
2. ADP and GDP promote the equilibrium toward alpha ketoglutarate, and ATP and GTP promote the equilibrium toward glutamate |
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Term
| Describe the shuttling system for removal of nitrogen via alanine |
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Definition
1. Pyruvate is formed in the last step of glycolysis
2. An amino group is attached to it to make alanine (via aminotransferase)
3. Alanine is sent from the muscle to the liver where the reverse reaction happens and pyruvate is formed and nitrogen is removed
4. Pyruvate can now undergo gluconeogenesis to remake glucose |
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Term
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Definition
| The shuttling between amino acid and alpha keto acid by the addition or removal of ammonia |
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Term
| What enzyme catalyzes and sets the pace of the urea cycle? |
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Definition
| Carbomoyl Phosphate Synthetase I |
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Term
| What is the rate limiting step in the urea cycle and describe its regulation |
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Definition
| the enzyme Carbamoyl Phosphtate Synthetase I is activated allosterically by N-acetylglutamate (more glutamate involvement in the cycle) |
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Term
| Where do the first steps of the urea cycle happen in a cell? |
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Definition
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Term
| Describe the steps in the urea cycle |
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Definition
1. CO2 and NH3 combine (via CPS I and 2ATP) to make Carbamoyl-PO4
2. Carbamoyl-PO4 reacts with ornithine (via ornithine transcarbamoylase) to make Citruline (an amino acid)
3. Citruline goes out of the mitochondrion
4. Citrulline reacts with aspartate (via argininosuccinate synthetase and ATP) to make argininosuccinate
5. Argininosuccinate lyase cleaves argininosuccinate into arginine and fumarate
6. Arginine is cleaved by arinase to make urea and ornithine |
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Term
| How is citruline moved into and out of the cell? |
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Definition
| A cotransnporter coupled with moving ornithine into the cell |
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Term
| Defects in the NAGS and CPS I steps of the urea cycle manifest how? |
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Definition
| Hyperammonemia (increased levels of ammonia in the blood) |
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Term
| How does a defect in the ornithine transcarbamylase enzyme manifest? |
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Definition
1. Increased Carbamoyl-PO4 spills into the cytoplasm
2. Reacts with CPS II leading to increased level of orotic acid and pyrimidines |
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Term
| How does a defect in the argininosuccinate synthetase enzyme manifest? |
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Definition
1. Increased levels of citrulline in CYTOPLASM
2. slight increase in ammonia levels |
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Term
| How does a defect in the argininosuccinate lyase enzyme manifest? |
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Definition
1. Increased levels of agininosuccinate
2. slightly higher levels of ammonia |
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Term
| How does a defect in the arginase enzyme manifest? |
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Definition
1. Buildup of arginine
2. slightly increased levels of ammonia |
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Term
| How does a defect in the ornithine/citrulline transporter manifest? |
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Definition
1. Increased ornithine in the cytosol
2. Increased Carbamoyl-PO4 in the mitochondrion (no ornithine to react with)
3. Increased ammonia levels |
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Term
| What are the treatment regimines for defects in the urea cycle? |
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Definition
1. Restrict protein in the diet - keeps the need for the urea cycle to a minimum
2. Supplement with amino acids
3. Medication - Sodium benzoate and phenylbutyrate can make glycine and glutamine water soluble, allowing them to be removed with urine |
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