MMT: amino acid catabolism II Flashcards
What is hyperammonemia?
High levels of ammonia due to a defect in the urea cycle or liver damage
What happens if we have a buildup of ammonia?
Ammonia in the brain will form glutamine that will cause osmotic imbalance and brain damage
What is the presentation of hyperammonemia?
Lethargy, hypotonia, vomiting, seizures if there is brain damage
How can we treat an N-acetylglutamate synthase deficiency?
N-carbamoyl glutamate injections
How can we treat an ornithine transcarbomylase deficiency?
Sodium benzoate and phenylbutyrate administration
Carbamoyl phosphate is built up in a patient. What are they deficient in?
OTC
What is orotic acid?
Built up carbamoyl phosphate from OTC deficiency form orotic acid
What does orotic aciduria indicate?
OTC deficiency or UMP synthase deficiency
How can we differentiate between UMP synthase and OTC deficiency?
UMP deficiency will lead to megaloblastic anemia and no hyperammonemia, while OTC deficiency causes hyperammonemia and low BUN
CPS I and OTC deficiencies lead to a buildup of…
Glutamine and glycine
How can we treat a CPS I and OTC deficiency?
Sodium benzoate and phenylbutyrate administration; benzoate makes glycine excretable and phenylbutyrate makes glutamine excretable
What does argininosuccinase do?
Form arginine from arginosuccinate
How can we treat an argininosuccinase deficiency?
Arginine supplementation
A person is deficient in arginosuccinate and is given exogenous arginine. How will ammonia from the TCA cycle be excreted now?
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
How can we treat an arginase deficiency?
A low protein diet
What is special about leucine and lysine?
They are strictly ketogenic
What are the steps in catabolism of methionine?
Methionine cycle, trans-sulfuration pathway, conversion to succinyl CoA
Describe the methionine cycle.
Converts methionine to homocysteine. Half of the homocysteine re-enters the cycle, and the other half moves on to the next phase
What does methionine synthase do?
Convert homocysteine back to methionine by using a methyl group
What cofactors does methionine synthase need?
5-methyl THF and B12
What important intermediate does the methionine cycle generate?
SAM, a really important methyl donor
Describe the second phase of methionine catabolism.
Cystathionine b-synthase forms a-ketobutyrate and cysteine. A-ketobutyrate becomes propionyl CoA and cysteine becomes pyruvate
What is true about cysteine and the catabolism of methionine?
The pathway makes cysteine a non-essential amino acid
What cofactor does Cystathione b-synthase need?
PLP
What does propionyl COA carboxylase do?
Convert propionyl CoA to d-methylmalonyl CoA
What coenzyme does propionyl CoA carboxylase need?
Biotin
What does methylmalonyl CoA mutase do?
Convert methylmalonyl CoA to succinyl CoA
What coenzyme does methylmalonyl CoA need?
B12
What amino acids can be used to make propionyl CoA?
Isoleucine, methionine, threonine, valine
What is homocystinuria?
A buildup of homocysteine due to defects in the methionine cycle. Homocysteine molecules combine to form homocystine
What are the symptoms of homocystinuria?
Lens subluxation, atherosclerosis (increased risk of stroke and MI)
Describe a cystathionine b-synthase deficiency.
Inability to convert homocysteine to cystathionine and eventually cysteine.
How do we treat cystathionine deficiency?
Decreased methionine intake and increased cysteine, B12, and folate intake
How do we treat a decreased affinity of cystathionine b-synthase for PLP?
Increased B6 in the diet
How do we treat methionine synthase deficiency?
Decreased methionine intake and supplemental trimethylglycine
What is propionic acidemia?
Defect in propionyl CoA carboxylase leads to a buildup of propionic acid and propionylcarnitine
What are symptoms of propionic acidemia?
Hypoglycemia from lack of gluconeogenesis, secondary hyperammonemia
How do we treat propionic acidemia?
Low protein diet, especially IMTV, and carnitine supplementation
What is methylmalonic acidemia?
Dysfunctional methylmalonyl CoA mutase leads to a buildup of methylmalonic acid as well as propionic acid (backs up the pathway) and methylmalonylcarnitine
How do we treat methylmalonic acidemia?
Low protein diet, carnitine, B12
