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72 Cards in this Set
- Front
- Back
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what are the three major steps of amino acid degradation?
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1) nitrogen removal, 2) clearance of NH4 and 3) utilizing carbon backbone
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what are the three was in which nitrogen can be removed?
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transamination, deamination, deamidation.
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what three molecules forms urea?
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NH4, one NH2 from aspartate and a carbon from carbon dioxide.
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what percentage of nitrogen is released via urea/ day?
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80-90%
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what are the minor nitrogen compounds found in the urine?
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bilirubin derivatives, hormones, and neurotransmitters.
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glutamine to glutamate is an example of : deamination or deamidation
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deamidation
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what three organs contribute to the metabolic sources ammonia?
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brain, muscle and gut
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in relation to nitrogen removal, what are the four amino acids that can actually undergo deamination?
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glutamate, threonine, serine, and histidine
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in relation to nitrogen removal, what are the 2 amino acids that can undergo deamidation?
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glutamine and asparagine
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how does NH3 indirectly help balance the pH of the urine?
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NH3 aids in the secretions of protons into the urine
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which reaction provides most of the NH4 in the urine?
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glutamine to glutamate via glutaminase
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what is removed in deamination? deamidation?
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alpha amino acid; amide group
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what is transfered in transamination?
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the alpha amino group from the amino acid to the alpha- ketoacid
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T/F
Transamination is involved in both the synthesis and degradation of amino acids. |
TRUE!
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T/F
transamination is irreversible. |
FALSE!
transamination is reversible. |
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what two amino acids cannot do transamination?
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threonine and lysine
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what is the cofactor for transamination? what is it derived from?
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Pyridoxal phosphate; vitamin B6
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when are ALT and AST released?
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after cell death or injury
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what is measured to reflect ALT and AST activity?
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the loss of the NADPH in the second reaction.
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what are the two mechanisms in which ammonia is controlled?
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1) Transamination takes the alpha amino group and puts it on the glutamate instead of letting it be a free compound. 2) three enzymes can fix "free" ammonia into organic molecules.
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what are the three enzymes that can "fix" ammonia into organic molecules?
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Carbamoyl phosphate synthetase, glutamine
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what are the three main functions of glutamate for the urea cycle?
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it collects nitrogen from other compounds by transamination, its donates NH4 via deamination by glutamate dehydrogenase, and indirectly by transaminating oxaloacetate into aspartate which then donates its nitrogen group to the urea cycle.
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where does urea synthesis take place?
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in the liver
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what is the main amino acid that carries nitrogen from other areas of the body besides the liver? what is the secondary amino acid?
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alanine; glutamine
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what are the two purposes of alanine in the liver (when transported by an outside source)?
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removal of nitrogen via the urea cycle and gluconeogenesis
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what converts glutamate to alanine?
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alanine transaminase
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how is glutamate primarily formed in peripheral tissues?
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via transamination
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what are the two net glutamate producers?
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brain and muscle
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what are the three main glutamate users?
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immune cells, gut and kidney
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where does the urea cycle start and where does it end?
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mitochondria and cytosol
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what converts bicarb and ammonia to Carbamoyl phosphate? where?
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carbamoyl phosphate synthase I in mitochondria
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how is the synthesis of carbamoyl phosphate regulated?
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regulated by the substrate which is ammonia and it is allosterically regulated by N-acetyl-glutamate.
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what does a deficiency in CPS 1 cause?
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Type 1 hyperammonemia
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which steps of the mitochondrial portion of the urea cycle require ATP?
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conversion of bicarb and ammonia to carbamoyl phosphate via CPS 1
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what is an alternate way in which carbamoyl phosphate can be produced?
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glutamine and carbon dioxide can be converted by carbamoyl phosphate synthase II (cytosol) in the pyrimidine synthesis pathway
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in relation to regulation of mitochondrial CPS I, an accumulation of arginine will cause what?
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an increase in ornithine production and an increase in N-acetyl-glutamate production. The increase in ornithine leads to an increase urea production and the increase in N-acetyl-glutamate causes an increase in CPS 1 activity which leads to an increase in urea production.
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what enzyme catalyzes citrulline synthesis? where does this conversion take place?
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ornithine transcarbamoylase; mitochondria
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what transports ornithine into the mitochondria? what is a deficiency in this enzyme called?
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ornithine translocase; HHH syndrome
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a deficiency of ornithine transcarbamoylase will cause what?
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Type 2 hyperammonemia
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where can citrulline and ornithine be produced?
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in the intestines
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what enzyme catalyzes the conversion of citrulline to argininosuccinate? where does this conversion take place?
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argininosuccinate synthetase; cytosol
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T/F
argininosuccinate synthesis is reversible |
FALSE.
its irreversible because it requires 1 ATP to be created |
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what else is needed in argininosuccinate synthesis besides ATP, citrulline, and argininosuccinate synthetase?
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aspartate
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what does a deficiency in argininosuccinate synthetase cause?
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citrullinuria type 1
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argininosuccinate produces what 2 compounds when argininosuccinate lyase is added?
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fumerate and arginine
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what is the purpose of the fumarate reentering the TCA cycle after being produced from argininosuccinate?
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to regenerate oxaloacetate and then aspartate.
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what does a deficiency in argininosuccinate lyase cause?
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argininosuccinyl acidemia
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what is the released product when glutamate is transaminated to form aspartate?
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alpha ketoglutarate
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what step links the urea cycle and the TCA cycle?
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the argininosuccinate step in which aspartate from the TCA cycle is used in conjunction with the citrulline from the urea cycle to form both arginine (for Urea) and fumarate (TCA).
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what step in urea cycle is urea actually released?
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conversion of arginine to ornithine.
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how many energy bonds are broken during the urea-TCA coupled cycle? how is the energy recovered?
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4; when fumarate reenters the TCA cycle
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arginine can be reduced to citrulline and what other compound?
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NO = nitric oxide
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what catalyzes the conversion of arginine to ornithine? what does a deficiency is this cause?
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arginase; argininemia
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where does ornithine go once it is produced?
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it moves into the mitochondria so it can be used in the urea cycle again to react with another molecule of carbamoyl phosphate
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arginine can be used for 2 other mechanisms other than the urea cycle, what are they?
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protein synthesis and NO synthesis
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what are the 5 ways of regulation of the urea cycle?
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concentration of the intermediates of the urea cycle (citrulline, ornithine, and arginine), concentration of N-acetyl-glutamate, High protein diet, concentration of substrates and a high ratio of protein degradation/synthesis in the body
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what are the 4 central roles of glutamate in urea cycle regulation?
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produces substrate ammonia via deamination, produces substrate aspartate via transamination, is a precursor for the required by N-acetyl-glutamate, and is a precursor for ornithine synthesis that is independent from the urea cycle
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T/F
Generally, low glutamate concentration favors increased urea synthesis |
FALSE
HIGH glutamate concentration favors increased urea synthesis. |
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during fasting, what is the main amino acid that is converted to glucose? what happens to the urea level in the urine?
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alanine; increases due to an increase in nitrogen of used amino acids has to be excreted.
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during long term fasting, how does the source of energy for the brain change? what happens to the urea level in the urine?
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Changes from glucose to ketone bodies; decreases due to a decrease in nitrogen of used amino acids has to be excreted.
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what is hyperammonemia?
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a deficiency in urea cycle enzymes that leads to increase ammonia levels in the blood
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what are the symptoms of hyperammonemia?
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encephalopathy, seizures, ataxia, loss of appetite, nausea, vomiting, lethargy and if left untreated, death.
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how is blood ammonia measured?
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via test tube GHD reaction and ammonia specific electrode
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what are the six primary types of hyperammonemia?
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type 1 and 3, citrullinuria type 1, argininosuccinic acidemia, argininemia and HHH syndrome
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what are the five secondary types of hyperammonemias?
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hepatic failure, lysinuric protein intolerance, hyperammonemia/ hyperinsulinism disorder, proprionic acidemia, and methylmalonic acidemia.
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which 2 of the types of hyperammonemia are not autosomal recessive? what are they?
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type 2 hyperammonemia (X-linked recessive) and hyperammonemia/ hyperinsulinism disorder (autosomal dominant)
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T/F
type 2 hyperammonemia has a high concentration of urine orotate. |
TRUE!
because type 2 hyperammonemia is a deficiency in ornithine transcarbamoylase, ornithine accumulates and cannot be converted to citrulline |
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which hyperammonemia disorder has extremely high concentration of ornithine?
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HHH syndrome
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what are the three types of treatments used for urea cycle disorders?
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low protein diet, drugs and arginine supplements
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what must be deficient in order for arginine supplements to work?
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argininosuccinate lyase
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Benzoic acid + glycine =
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hippuric acid which is excreted
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phenylbutyrate + glutamine =
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phenylacetylglutamine which is excreted
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