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WVSOM -- Protein and AA Metabolism and the Urea Cycle

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Question
Answer
Patient with Hepititis A has what type of elevated bilirubin levels?   indirect Bilirubin  
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Why is nitrogen metabolism important?   We need amino acids and they cannot be stored.  
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Is nitrogen secreted?   not generally  
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What are amino acids broken down for?   fuel or building blocks glucose and lipid synthesis  
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What does the breakdown of amino acids generate?   ammonia  
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Is ammonia toxic?   yes  
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What is ammonium?   NH4, an ion  
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What will cross the cell membrane, ammonia or ammonium?   ammonia  
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pK is 9.3 so at pH 7 which form predominates, ammonia or ammonium?   ammonium  
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Why is ammonia toxic?   It increases pH which alters redox balance and can disrupt protein structure/function as well as inhibiting oxidative phosphorylation by breaking down the H+ gradient  
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Where do we get our amino acids?   dietary proteins, endogenous protein and endogenous AA synthesis  
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What do amino acids break down into?   carbon and nitrogen  
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What do we do with carbon from AA degeneration?   energy and synthesis of glucose, FA and ketones  
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What do we do with nitrogen from AA degeneration?   urea  
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What do we synthesis with amino acids?   N-containing molecules such as purines, pyrimidines, porphyrins, neurotransmitters, etc.  
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What is Nitrogen Balance?   nitrogen input – nitrogen output  
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What is positive N balance?   input > output  
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What is negative N balance?   input<output  
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When do we see a positive N balance?   Childhood and pregnancy  
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When do we see a negative N balance?   dietary deficiency and catabolic stress  
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What are the 10 essential amino acids?   phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histidine, arginine, lysine, leucine  
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What is the neumonic for remembering the 10 essential amino acids?   PVT TIM HALL  
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Why is histidine an essential amino acid when it is synthesized in the urea cycle?   It is needed for growth and we don’t make enough  
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How is aspartate synthesized?   transanimation from oxaloacetate  
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Tyrosine is made from?   phenylalanine  
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Arginine is generated in?   the urea cycle  
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Glutamine is made from?   transanimation of glutamate  
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What are aminotransferases?   intracellular proteins not usually found in plasma. It is a transaminase  
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What are the tree cofactors important for AA synthesis?   pyridoxal phosphate, tetrahydrofolate and tetrahydroblopterin  
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Why is pyridoxal phosphate important?   for reactions involving the amino group (transamination and deamination)  
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What is tetrahydroblopterin required? BH4 is required for synthesis of tyrosine from phenylalanine    
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Where does protein digestion start?   stomach. HCl denatures the proteins to free AA  
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Where are free AA absorbed?   small intestine  
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How are AA absorbed in the small intestine?   facilitative diffusion and secondary active transport  
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What is done with incompletely digested protein?   utilized by bacteria releasing ammonia  
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How are AA transported?   Na dependent AA carriers  
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What is cystinurea?   defect in a transporter for cysteine and basic AA that results in kidney stones?  
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What is Hartnup disease?   defect in the transporter for neutral AA generally asymptomatic  
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What happens to the amino acids we dno’t need for protein synthesis?   amino group is removed thru transamination or deamination  
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What is more common transamination or damination?   transamination  
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What catalizes transamination?   aminotransferases  
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What is transamination?   conversino from keto acid to amino acid or vice versa  
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What does Aspartate go to?   asparagine  
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What does pyruvate go to?   alanine  
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What does serine go to?   glycine or cysteine  
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What does glutamate go to?   Glutamine  
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Glutamate semialdehyde goes to?   proline and arginine  
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How is pyridoxal phosphate synthesized and where?   In the liver from vitamin B6  
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What is B6 deficiency associated with?   drugs, alcoholism and starvation  
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how does glutamate get rid of the nitrogen?   Damination by glutamate dehydrogenase(GDH)  
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What is produced when glutamate is deaminated?   ammonia and alpha-ketoglutarate  
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Where does deamination of glutamate occur?   liver and kidney  
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Deamination of glutamate results in…   Glutamate + NH4 -> Alpha ketoglutinate + Ammonium  
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How many ammonium molecules does glutamine carry to the liver?   2  
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What is pyruvate transaminated to?   alanine  
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What does alanine give an amino group to in order to go back to pyruvate?   glutamate  
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Nitrogen component in AA catabolism is transferred to _________ where it is carried to the liver.   glutamate and glutamine  
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What are glucogenic AA?   degraded to pyruvate or TCA cycle intermediates  
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What are ketogenic AA?   degraded to acetyl CoA or acetoacetate  
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What does insulin promote with AA?   uptake and protein synthesis  
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What do glucocorticoids induce?   ubiquitin synthesis  
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Cortisol stimulates?   gluconeogenesis  
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Glucagaon and cortisol stimulate   uptake of AAs into the liver  
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What tissues metabolize AAs more rapidly?   kidney, brain, gut, immune cells  
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What hormone will lead to muscle wasting in fasting state?   cortisol  
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What is a hypercatabolic state?   state of increased fuel usage  
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What may cause a hypercatabolic state?   surgery, infection, trauma  
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What does the brain need AA for?   synthesis of neurotransmitters  
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What is a major source of AA in the fasted state?   muscle  
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What is the important hormone in a hypercatabolic state?   cortisol  
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What is urea?   disposal form of ammonia  
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Where is urea made?   urea cycle  
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What enzyme is used to go from ornithine to citrulline?   OTC Ornithine transcarbomylase  
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What enzyme is needed to go from HCO3 + NH4 -> Carbaoyl phosphate?   Carbamoyl Phospahte synthase 1  
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Is the synthesis of urea reversible?   no  
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Where do the first two steps of urea cycle take place?   mitochondria  
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What is the rate limiting step?   CPS1  
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What links the TCA cycle to the urea cycle?   fumerate  
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What is regenerated in the urea cycle?   ornithine  
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Where does the urea cycle primarily take place?   liver  
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Is ATP used in urea cycle?   yes  
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Where do the two N come from?   Ammonia and aspartate  
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How many N come from the urea cycle?   2  
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How is the urea cycle regulated?   based on substrate availability (feed forward)  
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What kind of diet induces urea cycle enzymes?   high protein or prolonged fasting  
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What stimulates CPS1?   NAG (n-acetylglutamate)  
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What synthesizes NAG?   aceytl CoA and glutamate  
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What happens to the urea produced in urea cycle?   crosses membranes and diffuses into the blood and is then filtered by the kidneys. Some diffuses into intestines where it is cleaved by bacteria  
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What is Blood urea Nitrogen?   BUN is a measure of urea concentration in the blood. Reflects function of the kidney and liver.  
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A patient is suffering from kidney failure. Would this patient have elevated or reduced BUN?   elevated  
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Urea cycle impairment results in?   hyperammonemia  
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What is hyperammonemia?   increased blood levels of ammonia  
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What are symptoms of hyperammonemia?   tremors, agitation, slurring of speech, blurred vision, vomiting, hypotonia, sezures, mental retardation, cerebral edema, coma  
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What is the most common urea cycle disorder?   OTC, ornithine transcarbamylase deficiency  
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What is OTC?   Ornithine transcarbamylase deficiency which is X-linked  
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How are hereditary urea cycle disorders passed on (except OTC)?   Autosomal recessive  
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