Biochem - Metabolism (Amino Acids, Urea cycle, Ammonia, & Associated Disorders) Flashcards
Pg. 108-109 in First Aid 2014 Sections include: -Amino acids -Urea cycle -Transport of ammonia by alanine and glutamate -Hyperammonemia -N-acetylglutamate deficiency -Ornithine transcarbamylase deficiency
What form of amino acids are found in proteins?
Only L-form of amino acids are found in proteins
Which is required regarding essential amino acids?
All essential amino acids need to be supplied in the diet
What are 3 glucogenic essential amino acids?
Glucogenic: (1) Methionine (Met) (2) Valine (Val) (3) Histidine (His)
What are 4 glucogenic/ketogenic essential amino acids?
Glucogenic/Ketogenic: (1) Isoleucine (Ile) (2) Phenylalanine (Phe) (3) Threonine (Thr) (4) Tryptophan (Trp)
What are 2 ketogenic essential amino acids?
Ketogenic: Leucine (Leu), Lysine (Lys)
What are 2 acidic (non-essential) amino acids? What is their charge at body pH?
(1) Aspartic acid (Asp) and (2) Glutamic acid (Glu). Negatively charged at body pH
What are 3 basic amino acids? Of these, which is most basic, and which has no charge at body pH?
(1) Arginine (Arg) (2) Lysine (Lys) (3) Histidine (His); Arg is most basic. His has no charge at body pH.
Which 2 basic amino acids are required during periods of growth?
Arg and His are required during periods of growth.
Which 2 basic amino acids are high in histones?
Arg and Lys are high in histones, which bind negatively charged DNA
What metabolic benefit results from amino acid catabolism?
Amino acid catabolism results in the formation of common metabolites (e.g., pyruvate, acetyl-CoA), which serve as metabolic feuls
How is urea related to amino acids?
Excess nitrogen (NH3) generated by this process (i.e., amino acid cataboism) is converted to urea and excreted in the kidneys
Name the 8 major substrates of the urea cycle.
(1) Ornithine (2) Carbamoyl phosphate (3) Citruline (4) Aspartate (5) Argininosuccinate (6) Fumarate (7) Arginine (8) Urea; Think: “Ordinarily, Careless Crappers Are Also Frivolous About Urination”
Draw the structure of Urea, indicating the source of its 3 major structural components.
See p. 108 in First Aid 2014 for visual near bottom of page
What reaction of the urea cycle occurs in the mitochondria? What is the required cofactor?
Carbamoyl synthetase I (requires N-acetylglutamate cofactor) converts CO2 + NH3 to Carbamoyl phosphate, which joins with Ornithine; They are converted to Citrulline by Ornithine transcarbamylase
Where does the majority of the urea cycle occur?
Cytoplasm (liver)
Draw the urea cycle, indicating the major steps catalyzed by the following enzymes: (1) Carbamoyl phosphate synthetase I (2) Ornithine transcarbamylase (3) Argininosuccinate synthetase (4) Argininosuccinase (5) Arginase.
See p. 108 in First Aid 2014 for visual at bottom of page
Draw a diagram depicting the transport of ammonia by alanine and glutamate in the muscle and liver. Highlight the alanine versus cori cycles in this process.
See p. 109 in First Aid 2014 for visual at top of page
What are the 3 major players in the alanine cycle? Draw it.
Glucose => Pyruvate => Alanine; See p. 109 in First Aid 2014 for visual at top of page
What are the 3 major players in the cori cycle? Draw it.
Glucose => Pyruvate => Lactate See p. 109 in First Aid 2014 for visual at top of page
What are 2 types of hyperammonemia? Give an example of each.
Can be acquired (e.g., liver disease) or hereditary (e.g., urea cycle enzyme deficiencies)
What metabolic effects does hyperammonemia have?
Results in excess NH4+, which depletes alpha-ketoglutarate, leading to inhibition of TCA cycle
What is the treatment for hyperammonemia? Explain mechanisms behind this.
Treatment: Limit protein in diet. Benzoate or phenylbutarate (both of which bind amino acid and lead to excretion) may be given to lower ammonia levels. Lactulose to acidify the GI tract and trap NH4+ for excretion.
What are 6 symptoms associated with Ammonia intoxication?
Ammonia intoxication - tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision
What is the purpose of N-acetylgutamate? What does its deficiency cause?
Required cofactor for carbamoyl phosphate synthetase I. Absence of N-acetylglutamate => hyperammonemia.
To what other condition is the presentation of N-acetylglutamate deficiency identical? What distinguishes these two conditions?
Presentation is identical to carbamoyl phosphate synthetase I deficiency. However, increased ornithine with normal urea cycle enzymes suggests hereditary N-acetylglutamate deficiency
What is the most common urea cycle disorder?
Ornithine transcarbamylase deficiency
What is the mode of inheritance of ornithine transcarbamylase deficiency?
X-linked recessive (vs. other urea cycle enzyme deficiencies, which are autosomal recessive).
What 2 major metabolic consequences does ornithine transcarbamylase deficiency have?
Interferes with body’s ability to eliminate ammonia; Excess carbamoyl phosphate is converted to orotic acid (part of pyrimidine synthesis pathway)
When is ornithine transcarbamylase deficiency often evident?
Often evident in first few days of life, but may present with late onset.
What are 4 clinical findings associated with ornithine transcarbamylase deficiency?
Findings: (1) Increased orotic acid in blood and urine (2) Low BUN (3) Symptoms of hyperammonemia. (4) No megaloblastic anemia (vs. orotic aciduria)
How does ornithine transcarbamylase deficiency relate to the pyrimidine synthesis pathway?
Excess carbamoyl phosphate is converted to orotic acid (part of pyrimidine synthesis pathway)
