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Rogers Flashcards

  1. What is the main source of nitrogen for the body?
    Amino Acids
  2. What are the two conditionally non-essential amino acids, and what essential amino acid are they derived from?
    • Tyrosine -- from phenylalanine
    • Cytosine -- from methionine
  3. Amino acids are broken down into what two components? Which is sent to the Krebs cycle? Where is the other one sent?
    • alpha-Keto Acids and NH4+ (ammonia)
    • alpha-Keto Acids go to Krebs
    • Ammonia goes to Urea Cycle
  4. In the breakdown of amino acids, the first task the cell must accomplish is the removal of the alpha-amino group. What are the two mechanisms involved?
    • Transamination
    • Oxidative Deamination (of glutamate only)
  5. In the transamination step of amino acid breakdown, alpha-Ketoglutarte + an amino acid (alanine or aspartate) are converted to glutamate + alpha-keto
    acid (pyruvate). The reverse reaction also occurs. What enzyme catalyzes this reaction? What co-factor is required?
    • Aminotransferase
    • Pyridoxal Phosphate (PLP) (coenzyme form of Vit B6)
  6. Aminotransferases (used to catalyze the breakdown of amino acids) have an important diagnostic value. Both aspartate AT and alanine AT levels in the plasma are elevated in what three diseases/defects?
    • Liver Diseases
    • Myocardial Infarction
    • Muscle Disorders
  7. Pyridoxal Phosphate (PLP), the coenzyme required for all ATs, is converted to __________ ___________ upon acceptance of an amino group
    Pyridoxamine Phosphate (PMP)
  8. In the Oxidative Deamination step of amino acid breakdown, L-glutamate + water is converted to alpha-ketoglutarate + ammonia. what enzyme catalyzes this reaction? What is the reverse reaction known as?
    • Glutamate Dehydrogenase
    • Reductive Amination
  9. Glutamate dehydrogenase, the enzyme utilized in the oxidative deamination step of amino acid breakdown, can use which two molecules as a coenzyme? What are the allosteric regulators of the enzyme, and what are their effects?
    • NAD+ or NADP+
    • ATP & GTP (inhibitors)
    • ADP & GDP (activators)
  10. Ammonia (NH4+) can be converted to its non-toxic form in what organ?
    Liver
  11. The transport of nitrogen from other organs and tissues to the liver is carried out by what two amino acids?
    • Alanine
    • Glutamine
  12. What is the major amino acid responsible for the transportation of nitrogen from muscle tissue to the liver? What is this process called?
    • Alanine
    • Glucose-Alanine Cycle
  13. What is an important amino acid in the transport of nitrogen, as it can directly use NH4+ in its synthesis. This reaction also plays a key role in the kidney in the regulation of blood pH.
    Glutamine
  14. In the first step of the Urea Cycle, CO2 + NH4+ are converted to Carbamoyl Phosphate. What enzyme catalyzes this reaction?
    Carbamoyl Phosphate Synthetase I
  15. In the second step of the Urea Cycle, Carbamoyl Phosphate + L-Ornithine are converted to L-Citrulline. What enzyme catalyzes this reaction?
    Ornithine Transcarbamoylase
  16. In the third step of the Urea Cycle, L-Citrulline is converted to Argininosuccinate. What enzyme catablyzes this reaction?
    Agininosuccinate Synthetase
  17. In the fourth step of the Urea Cycle, Argininosuccinate is converted to L-Arginine. What enzyme catalyzes this reaction? What is an important by-product of this reaction?
    • Argininosuccinate Lyase
    • Fumarate
  18. In the fifth step of the Urea Cycle, L-Arginine is converted to L-Ornithine. What enzyme catalyzes this reaction? What is excreted as a result of this reaction? Where does the L-Ornithine go?
    • Arginase
    • Urea
    • Goes to combine with Carbamoyl Phosphate, which is converted to L-Citrulline in the second step of the Urea Cycle
  19. Where are the two nitrogens present in Urea derived from?
    • Ammonia (combine with carbon dioxide in the first step of reaction to generate carbamoyl phosphate)
    • Aspartate (a part of the agininosuccinate molecule that takes part in the third and fourth steps of the reaction)
  20. How many phosphates are used up in the Urea Cycle?
    4
  21. Glutamate is converted to Glutamine with the addition of what molecule? What enzyme catalyzes this reaction? What enzyme catalyzes the reverse reaction?
    • Glutamate + NH4+ to form Glutamine
    • Glutamine Synthetase
    • Glutaminase
  22. GABA is synthesized from Glutamic Acid through what enzyme?
    Glutamic Acid Decarboxylase
  23. What is the major form of disposal of amino groups from amino acids? This is a soluble, non-toxic compound that accounts for ~90% of the nitrogen-containing compounds of urine. It is produced by the liver and transported in the blood to the kidneys for excretion in the urine.
    Urea
  24. What is the major link between the Urea Cycle and the Krebs Cycle?
    The generation of Fumarate as a by-product of the conversion of Arginosuccinate to L-Arginine
  25. What is the rate-limiting step in the production of urea?
    Conversion of CO2 + NH4+ to Carbamoyl Phosphate (catalyzed by Carbamoyl Phosphate Synthetase)
  26. Carbamoyl Phosphate Synthetase (CPS I), the enzyme that catalyzes the rate-limiting step of the Urea Cycle, is activated by what?
    N-acetylglutamate
  27. What are the key roles of Glutamate in the Urea Cycle (3)?
    • Nitrogen atoms in urea originate from glutamate
    • Glutamate yields allosteric activator of CPS I
    • Glutamate is a precursor of Ornithine
  28. Elevated levels of ammonia in the blood are toxic to the CNS. what is the condition this causes called? What are its symptoms?
    • Hyperammonemia
    • Tremors, slurring of speech, and blurred vision
  29. What are the two types of Hyperammonemia?
    • Acquired Hyperammonemia: examples include cirrhosis of the liver and hepatitis
    • Hereditary Hyperammonemia: results from genetic deficiencies of the urea cycle enzymes
  30. Genetic deficiencies are seen in what 5 urea cycle enzymes in Hereditary Hyperammonemia? How are they inherited?
    • N-acetylglutamte synthetase (NGS): AR
    • Carbamoyl phosphate synthetase (CPS): AR
    • Ornithine transcarbamylase (OTC): X-linked
    • Argininosuccinate synthetase (AS): AR
    • Argininosuccinate lyase (AL): AR
  31. What is the most common Urea Cycle disorder? In what gender is this most common in?
    • Deficiency in Ornithine Transcarbamoylase (OTC)
    • Males bc X-linked
  32. What labs are often seen in deficiencies of Ornithine Transcarbamoylase (OTC)?
    • Elevated Plasma Ammonia Levels: >1000-3000 (normal levels are <50)
    • Elevated Glutamine, Alanine
    • Decreased Citrulline and Arginine
    • Urine Orotic Acid levels are greatly increased (orotate)
    • Decreased OTC activity in liver
  33. Why are urine orotic (orotate) levels increased in ornithine transcarbamoylase deficiencies (OTCs)?
    Because carbamoyl phosphate (in urea cycle) is at increased levels in the mitochondria --> goes into cytosol and penetrates into the pyramidine biosynthesis pathway --> orotate can't go forward in the pathway and so levels build up in the cytosol
  34. What is the long-term treatment for Ornithine Transcarbamoylase Deficiency (OTC)?
    Low Protein Diet
  35. Where do the first and second steps of the urea cycle occur?
    In the mitochondria
  36. Where do the third through fifth steps of the urea cycle occur?
    In the cytosol
  37. What are the short-term treatment options for Ornithine Transcarbamoylase Deficiency (OTC)?
    • Sodium benzoate conjugates with glycine to form hippurate
    • Phenylbutyrate is converted to phenylacetate, which becomes conjugated with glutamine to form phenylacetylglutamine
    • These products are excreted in the urine (can help rid the body of ammonia)
  38. The carbon skeletons of the 20 amino acids undergo a series of reactiosn that result in products that are members of the glycolytic pathway, the Krebs cycle, or ketoacids. What are the only seven products of these?
    • Pyruvate
    • Acetyl CoA
    • Acetoacetyl CoA
    • alpha-Ketoglutarate
    • Succinyl CoA
    • Fumarate
    • Oxaloacetate
  39. Amino Acids that are degraded to acetyl CoA or acetoacetyl CoA are called?
    Ketogenic Amino Acids
  40. Amino acids that are degraded to pyruvate, alpha-ketoglutarate, succinyl CoA, fumarate, or oxaloacetate are called?
    Glucogenic Amino Acids
  41. What amino acids are both Glucogenic and Ketogenic?
    • Isoleucine
    • Phenylalanine
    • Tyrosine
    • Tryptophan
  42. What amino acids are Ketogenic?
    • Leucine
    • Lysine
  43. What are three examples of genetic defects associated with amino acid catabolism?
    • Phenylketonuria (defect in the catabolism of phe)
    • Maple Syrup Urine Disease (defect in the catabolism of ile, leu, and val)
    • Homocystinuria (defect in the catabolism of met)
  44. Phenylketonuria (PKU) is a defect in the catabolism of what amino acid?
    Phenylalanine
  45. What is unique about the catabolism of phenylalanine?
    Transamination is not the first step of the pathway
  46. What are the three steps in the catabolism of phenylalanine?
    • Hydroxylation to form tyrosine
    • Transamination of tyrosine
    • Catabolism of the alpha-keto acid of tyrosine
  47. What enzyme catalyzes the hydroxylation of phenylalanine to form tyrosine, the first step in the catabolism of phenylalanine? What co-factor is involved, and what is it oxidized to? What other molecule is needed for this reaction?
    • Phenylalanine Hydroxylase
    • BH4 (Tetrahydrobiopterin) to BH2 (Dihydrobiopterin)
    • O2
  48. In the recycling of BH4 (tetrahydrobiopterin), what enzyme catalyzes the reduction from BH2 (Dihydrobiopterin) to BH4?
    Dihydropteridine Reductase
  49. Phenylketonuria is an autosomal recessive gene defect. In 99% of cases, what gene is affected? What symptoms are seen with this disease, if left untreated?
    • Phenylalanine Hydroxylase Gene
    • MR, CNS Damage, and Hypopigmentation
  50. In patients with PKU, what is phenylalanine transaminated to?
    Phenylpyruvate and Phenylacetate
  51. How is PKU diagnosed? When should this be done?
    • Determination of blood phenylalanine levels: (in PKU-- 1000 muM) -- normal = <50
    • Measurement shoudl be done >2 days after birth
  52. What is the treatment for PKU?
    • Restricted diet, with a goal to reduce but not
    • eliminate the intake of phenylalanine (don't eliminate completely bc is an essential amino acid)
    • Also want to make sure the pt gets the right amount of
    • tyrosine bc it becomes an essential amino acid with this deficiency
  53. What is an important consideration of maternal PKU?
    If a mom with PKU has a spike in phenylalanine levels during pregnancy, it can cause MR and congenital malformations in the fetus (even if the fetus has the normal gene)
  54. What are the biosynthetic products of a tyrosine build-up, as seen in PKU?
    • Proteins
    • Melanin -- leads to hypopigmentation
    • Catecholamine
    • Fumarate
  55. About 1% of PKU patients have a defect in a different gene. What is the gene, and what additional symptoms does it cause?
    • DHPR (dihydropteridine reductase gene)
    • Causes movement disorders due to reduced production of dopamine
    • Causes depression problems due to reduced production of serotonin
  56. What are the three branched-chain amino acids?
    • Isoleucine
    • Leucine
    • Valine
  57. What are the two steps in the catabolism of branched-chain amino acids?
    • Transamination: catalyzed by a branched-chain aminotransferase
    • Alpha-keto acid products are decarboxylated: catalyzed by branched-chain alpha-ketoacid dehydrogenase
  58. Maple-syrup urine disease (MSUD) is an autosomal recessive disease caused by a defect in the catabolism of what amino acid? What deficiency is seen in this disease?
    • Branched-chain amino acids
    • Deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKAD): occurs in the 2nd step of the catabolism of the branch-chain amino acids
  59. What are the symptoms of Maple-Syrup Urine Disease?
    • Onset occurs at 4-7 days of age
    • Lethargy, weight loss, damage to CNS, and often coma followed by death
    • Survivors suffer from MR
  60. How is maple-syrup urine disease diagnosed?
    • Large increase in the levels of branched-chain amino
    • acids, particularly leucine, in the plasma and urine
    • The presence of the metabolite of isoleucine (alloisoleucine) in the plasma and urine is diagnostic of this disease
    • The high levels of the alpha-keto acid of isoleucine
    • (2-oxy-3-methylvaleric acid) in the urine results in a smell similar to maple syrup
  61. What is the treatment for Maple-Syrup Urine Disease (MSUD)?
    Control intake of branched-chain amino acids in diet (don't eliminate completely bc essential amino acids)
  62. What secondary problem can Maple-Syrup Urine Disease lead to?
    Hyperammonemia: organic acids inhibit the enzyme N-acetylglutamate synthetase, which activates the first step in the urea cycle
  63. Homocystinuria is an autosomal recessive disease that resutls from a deficiency of what enzyme? This is a defect in the catabolism of what amino acid, and what build-up occurs?
    • Cystathionine Synthase
    • Methionine
    • Cysteine
  64. What symptoms are associated with Homocystinuria? How is this diagnosed?
    • Osteoporosis, MR, characteristic lens dislocation, and can lead to vascular probs (die of cardiovascular disease @ young age if left untreated)
    • Accumulation of homocysteine in the urine
  65. What are the treatment options for Homocystinuria?
    • Restrict methionine in diet
    • Megadoses of Vit B6 -- co-factor for defective enzyme
    • Supplements for Vit B12 and folic acid (enhances conversion of homocysteine back to methionine, which can stop the build-up of cysteine)
  66. Synthesis of non-essential amino acids:
    Alpha-ketoglutarate (intermediate in Krebs cycle) leads to ________, which leads to formation of _________, and _________.
    • Glutamate
    • Glutamine
    • Proline
  67. Glutamate is synthesized by a reductive amination reaction:
    Alpha-ketoglutarate + NH4+ -----> Glutamate

    What enzyme catalyzes this reaction, and what molecule is required?
    (glutamate can also be synthesized by a transamination reaction)
    • Glutamate Dehydrogenase
    • NADH + H --> NAD+
  68. Synthesis of non-essential amino acids:
    Oxaloacetate (intermediate in the Krebs cycle) ---> ________ ---> _______.
    • Asparate
    • Asparagine
  69. Synthesis of non-essential amino acids:
    Pyruvate (product of glycolysis) ---> _________.
    Alanine
  70. Synthesis of non-essential amino acids:
    3-phosphoglycerate (glycolysis intermediate) --->________, which ---> ________, and when added to methionine ---> __________.
    • Serine
    • Glycine
    • Cysteine
  71. Synthesis of non-essential amino acids:
    Aromatic amino acid synthesis:
    _________ is synthesized from phenylalanine.
    Tyrosine
  72. Glutamate + NH4+ ---> Glutamine

    What enzyme catalyzes this reaction? What molecule is necessary for the reaction to occur? What enzyme catalyzes the reverse reaction?
    • Glutamine Synthetase
    • ATP
    • Glutaminase
  73. Aspartate + Glutamine ---> Asparagine + Glutamate

    What enyzme catalyzes this reaction? What molecule is necessary for the reaction to occur?
    • Asparagine Synthetase
    • ATP
  74. Asparagine ---> Aspartate + NH4+

    What enzyme catalyzes this reaction?What implication does this reaction have for the treatment of some cancer patients?
    • Asparaginase
    • Some leukemic cells lose ability to make asparagine, which then becomes an essential acid. Therefore, a treatment for leukemia is adding asparaginase, which converts asparagine into aspartate. The lack of asparagine makes cancer cells less able to divide.
  75. 3-phosphoglycerate ---> 3-phosphohydropyruvate ---> 3-phosphoserine ---> Serine

    What enzyme catalyzes the 1st, 2nd, and 3rd reactions? What are the by-products?
    • Step 1: Enzyme: Dehydrogenase. NAD --> NADH + H
    • Step 2: Enzyme: Transaminase. Glutamate --> a-ketoglutarate
    • Step 3: Enzyme: Phosphatase. H2O --> Pi
  76. Met -->--> Homocysteine + Ser ---> Cystathionine ---> Cys

    What enzyme is used in the conversion from homocysteine to Cystathionine? What is given off when Cystathionine is converted to Cysteine?
    • Cystathionine Synthase (B6)
    • Alpha-ketobutyrate
  77. Phenylalanine ----> Tyrosine

    What enzyme catalyzes this reaction?
    What two molecules are required?
    • Phenylalanine Hydroxylase
    • O2 --> H2O
    • BH4 --> BH2
  78. What are the two One Carbon Transfer Units?
    • Tetrahydrofolate
    • S-adenosylmethionine (SAM)
  79. Which compound is the most versatile of the carriers of 1-C fragments and carries them at several levels of oxidation, from the most reduced (methyl) to the most oxidized (methenyl)? How is it taken into the diet?
    • Tetrahydrofolate (FH4)
    • As folic acid
  80. What three units is Tetrahydrofolate (TH4) composed of? How are the 1-C fragments carried?
    • A pteridine derivative
    • p-aminobenzoic acid (PABA)
    • Glutamic acid
    • The 1-C fragments are carried either on N5 or N10 or as a bridge between both
  81. What is the main amino acid involved in the synthesis of heme?
    Glycine
  82. In the first step in the synthesis of heme,
    Glycine + Succinyl CoA ----> delta-Aminolevulinic Acid (ALA)

    What enzyme catalyzes this reaction?What molecule is a negative feedback regulator of this reaction? What two molecules are given off in the course of this reaction? How many times must it occur to move into the next step of heme synthesis?
    • delta-Aminolevulinate Synthase (ALA Synthase)
    • Hemin Heme
    • CoA & CO2
    • 2
  83. In the second step of heme synthesis, the two molecules of delta-Aminolevulinic Acid (ALA) combine to form Porphobilinogen. What enzyme catalyzes this reaction? What molecule is a negative feedback inhibitor of this reaction? What molecule is given off in the course of this reaction? How many times must this reaction occur to move on to the next step in heme sythesis?
    • delta-Aminolevulinic Acid Dehydrogenase (ALA Dehydrogenase)
    • Lead
    • 2 H2O
    • 4
  84. In the third step of heme synthesis, the four Porphobilinogen molecules condense to form Hydroxymethylbilane. What enyzme catalyzes this reaction? What molecule is given off in the course of this reaction?
    • Hydroxymethylbilane Synthase
    • 4 NH3
  85. In the fourth step of heme synthesis, Hydroxymethylbilane ---> Uroporphyrinogen III

    What enzyme catalyzes this reaction? What happens during the course of this reaction?
    • Uroporphyrinogen III Synthase
    • Ring closure and isomerization
  86. In the fifth step of heme synthesis,
    Uroporphyrinogen III ---> Coproporphyrinogen III

    What enzyme catalyzes this reaction? What molecule is given off in the course of this reaction?
    • Uroporphyrinogen Decarboxylase
    • 4 CO2
  87. In the sixth and seventh steps of heme synthesis,
    Coproporphyrinogen III ----> Protoporphyrin IX ----> Heme (Fe2+ protoporphyrin IX)

    What enzyme catalyzes this reaction? What is added in the course of the reaction, and what is given off? What negatively inhibits this reaction?
    • Ferrochelatase
    • Fe2+ added; 2 H+ given off
    • Lead
  88. What two enzymes involved in heme synthesis are particularly sensitive to inhibition by lead (inhibited in lead poisoning). What two molecules build up as a result of this inhibition?
    • Ferrochelatase & ALA Dehydratase
    • Protoporphyrin IX & ALA
  89. In Acute Intermittent Porphyria, an autosomally-dominant acute disorder, what enzyme is deficient? What two molecules accumulate in the urine in the course of this disease, causing the urine to darken upon exposure to light and air? Are patients with this form of porphyria photosensitive?
    • Hydroxymethylbilane Synthase
    • Porphobilinogen and delta-Aminolevulinic Acid
    • NOT photosensitive
  90. Porphyria Cutanea Tarda is an autosomally-dominant, chronic disease caused by a deficiency in what enzyme involved in heme synthesis? What molecule accumulates in the urine. Are patients photosensitive?
    • Uroporphyrinogen Decarboxylase
    • Uroporphyrin
    • Are photosensitive
  91. How are most porphyrias treated? What is the most common porphyria? What is the main problem associated with porphyrias?
    • Porphyria Cutanea Tarda
    • Treated with a heme analogue
    • Pts don't make sufficient heme
  92. Where does heme degradation begin? In the first step,
    Heme ---> Biliverdin

    What enzyme is responsible for this reaction? What molecules are necessary, and what molecules are given off?
    • Spleen
    • Heme Oxygenase
    • O2, NADPH + H+ --> NADP+
    • Fe2+ & CO
  93. In the second step of heme degradation,
    Biliverdin ---> Bilirubin

    What enzyme catalyzes this reaction? What molecules are necessary for this reaction to take place?
    • Biliverdin Reductase
    • NADPH + H+ ---> NADP+
  94. In the third step of heme degradation, Bilirubin moves out of the spleen and enters the blood as a Bilirubin-Albumin Complex. It then moves into the liver, where
    Bilirubin ---> Bilirubin Diglucuronide

    What enzyme catalyzes this reaction? What molecule is necessary for this reaction to take place?

    Bilirubin diglucuronide then moves out of the liver as Bilirubin Diglucuronide and Bile
    • Bilirubin Glucuronyltransferase
    • 2-UDP-glucuronic acid ---> 2 UDP
Author
julieaburch
ID
76753
Card Set
Rogers Flashcards
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Rogers Flashcards
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