MMT: amino acid catabolism II

Question 1

What is hyperammonemia?

Answer 1

High levels of ammonia due to a defect in the urea cycle or liver damage

Question 2

What happens if we have a buildup of ammonia?

Answer 2

Ammonia in the brain will form glutamine that will cause osmotic imbalance and brain damage

Question 3

What is the presentation of hyperammonemia?

Answer 3

Lethargy, hypotonia, vomiting, seizures if there is brain damage

Question 4

How can we treat an N-acetylglutamate synthase deficiency?

Answer 4

N-carbamoyl glutamate injections

Question 5

How can we treat an ornithine transcarbomylase deficiency?

Answer 5

Sodium benzoate and phenylbutyrate administration

Question 6

Carbamoyl phosphate is built up in a patient. What are they deficient in?

Answer 6

OTC

Question 7

What is orotic acid?

Answer 7

Built up carbamoyl phosphate from OTC deficiency form orotic acid

Question 8

What does orotic aciduria indicate?

Answer 8

OTC deficiency or UMP synthase deficiency

Question 9

How can we differentiate between UMP synthase and OTC deficiency?

Answer 9

UMP deficiency will lead to megaloblastic anemia and no hyperammonemia, while OTC deficiency causes hyperammonemia and low BUN

Question 10

CPS I and OTC deficiencies lead to a buildup of…

Answer 10

Glutamine and glycine

Question 11

How can we treat a CPS I and OTC deficiency?

Answer 11

Sodium benzoate and phenylbutyrate administration; benzoate makes glycine excretable and phenylbutyrate makes glutamine excretable

Question 12

What does argininosuccinase do?

Answer 12

Form arginine from arginosuccinate

Question 13

How can we treat an argininosuccinase deficiency?

Answer 13

Arginine supplementation

Question 14

A person is deficient in arginosuccinate and is given exogenous arginine. How will ammonia from the TCA cycle be excreted now?

Answer 14

Instead of using the TCA cycle to form arginine, the cycle will continue as normal until it reaches arginosuccinate. This molecule can then be readily excreted, allowing us to get rid of the ammonia

Question 15

How can we treat an arginase deficiency?

Answer 15

A low protein diet

Question 16

What is special about leucine and lysine?

Answer 16

They are strictly ketogenic

Question 17

What are the steps in catabolism of methionine?

Answer 17

Methionine cycle, trans-sulfuration pathway, conversion to succinyl CoA

Question 18

Describe the methionine cycle.

Answer 18

Converts methionine to homocysteine. Half of the homocysteine re-enters the cycle, and the other half moves on to the next phase

Question 19

What does methionine synthase do?

Answer 19

Convert homocysteine back to methionine by using a methyl group

Question 20

What cofactors does methionine synthase need?

Answer 20

5-methyl THF and B12

Question 21

What important intermediate does the methionine cycle generate?

Answer 21

SAM, a really important methyl donor

Question 22

Describe the second phase of methionine catabolism.

Answer 22

Cystathionine b-synthase forms a-ketobutyrate and cysteine. A-ketobutyrate becomes propionyl CoA and cysteine becomes pyruvate

Question 23

What is true about cysteine and the catabolism of methionine?

Answer 23

The pathway makes cysteine a non-essential amino acid

Question 24

What cofactor does Cystathione b-synthase need?

Answer 24

PLP

Question 25

What does propionyl COA carboxylase do?

Answer 25

Convert propionyl CoA to d-methylmalonyl CoA

Question 26

What coenzyme does propionyl CoA carboxylase need?

Answer 26

Biotin

Question 27

What does methylmalonyl CoA mutase do?

Answer 27

Convert methylmalonyl CoA to succinyl CoA

Question 28

What coenzyme does methylmalonyl CoA need?

Answer 28

B12

Question 29

What amino acids can be used to make propionyl CoA?

Answer 29

Isoleucine, methionine, threonine, valine

Question 30

What is homocystinuria?

Answer 30

A buildup of homocysteine due to defects in the methionine cycle. Homocysteine molecules combine to form homocystine

Question 31

What are the symptoms of homocystinuria?

Answer 31

Lens subluxation, atherosclerosis (increased risk of stroke and MI)

Question 32

Describe a cystathionine b-synthase deficiency.

Answer 32

Inability to convert homocysteine to cystathionine and eventually cysteine.

Question 33

How do we treat cystathionine deficiency?

Answer 33

Decreased methionine intake and increased cysteine, B12, and folate intake

Question 34

How do we treat a decreased affinity of cystathionine b-synthase for PLP?

Answer 34

Increased B6 in the diet

Question 35

How do we treat methionine synthase deficiency?

Answer 35

Decreased methionine intake and supplemental trimethylglycine

Question 36

What is propionic acidemia?

Answer 36

Defect in propionyl CoA carboxylase leads to a buildup of propionic acid and propionylcarnitine

Question 37

What are symptoms of propionic acidemia?

Answer 37

Hypoglycemia from lack of gluconeogenesis, secondary hyperammonemia

Question 38

How do we treat propionic acidemia?

Answer 38

Low protein diet, especially IMTV, and carnitine supplementation

Question 39

What is methylmalonic acidemia?

Answer 39

Dysfunctional methylmalonyl CoA mutase leads to a buildup of methylmalonic acid as well as propionic acid (backs up the pathway) and methylmalonylcarnitine

Question 40

How do we treat methylmalonic acidemia?

Answer 40

Low protein diet, carnitine, B12