Biochem - Metabolism (Amino Acids, Urea cycle, Ammonia, & Associated Disorders)

Question 1

What form of amino acids are found in proteins?

Answer 1

Only L-form of amino acids are found in proteins

Question 2

Which is required regarding essential amino acids?

Answer 2

All essential amino acids need to be supplied in the diet

Question 3

What are 3 glucogenic essential amino acids?

Answer 3

Glucogenic: (1) Methionine (Met) (2) Valine (Val) (3) Histidine (His)

Question 4

What are 4 glucogenic/ketogenic essential amino acids?

Answer 4

Glucogenic/Ketogenic: (1) Isoleucine (Ile) (2) Phenylalanine (Phe) (3) Threonine (Thr) (4) Tryptophan (Trp)

Question 5

What are 2 ketogenic essential amino acids?

Answer 5

Ketogenic: Leucine (Leu), Lysine (Lys)

Question 6

What are 2 acidic (non-essential) amino acids? What is their charge at body pH?

Answer 6

(1) Aspartic acid (Asp) and (2) Glutamic acid (Glu). Negatively charged at body pH

Question 7

What are 3 basic amino acids? Of these, which is most basic, and which has no charge at body pH?

Answer 7

(1) Arginine (Arg) (2) Lysine (Lys) (3) Histidine (His); Arg is most basic. His has no charge at body pH.

Question 8

Which 2 basic amino acids are required during periods of growth?

Answer 8

Arg and His are required during periods of growth.

Question 9

Which 2 basic amino acids are high in histones?

Answer 9

Arg and Lys are high in histones, which bind negatively charged DNA

Question 10

What metabolic benefit results from amino acid catabolism?

Answer 10

Amino acid catabolism results in the formation of common metabolites (e.g., pyruvate, acetyl-CoA), which serve as metabolic feuls

Question 11

How is urea related to amino acids?

Answer 11

Excess nitrogen (NH3) generated by this process (i.e., amino acid cataboism) is converted to urea and excreted in the kidneys

Question 12

Name the 8 major substrates of the urea cycle.

Answer 12

(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”

Question 13

Draw the structure of Urea, indicating the source of its 3 major structural components.

Answer 13

See p. 108 in First Aid 2014 for visual near bottom of page

Question 14

What reaction of the urea cycle occurs in the mitochondria? What is the required cofactor?

Answer 14

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

Question 15

Where does the majority of the urea cycle occur?

Answer 15

Cytoplasm (liver)

Question 16

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.

Answer 16

See p. 108 in First Aid 2014 for visual at bottom of page

Question 17

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.

Answer 17

See p. 109 in First Aid 2014 for visual at top of page

Question 18

What are the 3 major players in the alanine cycle? Draw it.

Answer 18

Glucose => Pyruvate => Alanine; See p. 109 in First Aid 2014 for visual at top of page

Question 19

What are the 3 major players in the cori cycle? Draw it.

Answer 19

Glucose => Pyruvate => Lactate See p. 109 in First Aid 2014 for visual at top of page

Question 20

What are 2 types of hyperammonemia? Give an example of each.

Answer 20

Can be acquired (e.g., liver disease) or hereditary (e.g., urea cycle enzyme deficiencies)

Question 21

What metabolic effects does hyperammonemia have?

Answer 21

Results in excess NH4+, which depletes alpha-ketoglutarate, leading to inhibition of TCA cycle

Question 22

What is the treatment for hyperammonemia? Explain mechanisms behind this.

Answer 22

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.

Question 23

What are 6 symptoms associated with Ammonia intoxication?

Answer 23

Ammonia intoxication - tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision

Question 24

What is the purpose of N-acetylgutamate? What does its deficiency cause?

Answer 24

Required cofactor for carbamoyl phosphate synthetase I. Absence of N-acetylglutamate => hyperammonemia.

Question 25

To what other condition is the presentation of N-acetylglutamate deficiency identical? What distinguishes these two conditions?

Answer 25

Presentation is identical to carbamoyl phosphate synthetase I deficiency. However, increased ornithine with normal urea cycle enzymes suggests hereditary N-acetylglutamate deficiency

Question 26

What is the most common urea cycle disorder?

Answer 26

Ornithine transcarbamylase deficiency

Question 27

What is the mode of inheritance of ornithine transcarbamylase deficiency?

Answer 27

X-linked recessive (vs. other urea cycle enzyme deficiencies, which are autosomal recessive).

Question 28

What 2 major metabolic consequences does ornithine transcarbamylase deficiency have?

Answer 28

Interferes with body’s ability to eliminate ammonia; Excess carbamoyl phosphate is converted to orotic acid (part of pyrimidine synthesis pathway)

Question 29

When is ornithine transcarbamylase deficiency often evident?

Answer 29

Often evident in first few days of life, but may present with late onset.

Question 30

What are 4 clinical findings associated with ornithine transcarbamylase deficiency?

Answer 30

Findings: (1) Increased orotic acid in blood and urine (2) Low BUN (3) Symptoms of hyperammonemia. (4) No megaloblastic anemia (vs. orotic aciduria)

Question 31

How does ornithine transcarbamylase deficiency relate to the pyrimidine synthesis pathway?

Answer 31

Excess carbamoyl phosphate is converted to orotic acid (part of pyrimidine synthesis pathway)