L25 - 1C Metabolism and Some Products of Amino Acids Flashcards
Feb 22, 2019
PKU Type II is also called what? Why?
Malignant PKU as it is harder to treat than classical PKU
What causes malignant PKU?
Deficiency of dihydrobiopterin or tetrahydrobiopterin reductase
What are the three reactions for which BH4 is necessary?
1) Phe to Tyr
2) Tyr to L-dopa
3) 5-HT synthesis
What effect does PKU II have on tyrosine?
Tyrosine becomes an essential AA
What substances are produced in lower number in PKU II?
1) reduced melanin synthesis
2) reduced catecholamine synthesis
3) reduced tyrosine synthesis
One-carbon metabolism links amino acid metabolism and the metabolism of what other molecules?
nucleotides (nucleic acids)
What three vitamins/cofactors are necessary for 1-C transfers?
1) vitamin B9 (folate)
2) vitamin B12 (cobalamin)
3) SAM
SAM is a _____ donor. It is especially important in the formation of _______. After donating its carbon, it is converted into ________.
1) methyl
2) epinephrine
3) homocysteine
Homocysteine can be converted back to its original amino acid which is?
Methionine
What enzyme converts homocysteine into methionine?
methionine synthase
Homocysteine can be converted into ________ via the _________ pathway.
1) cysteine
2) transulfuration pathway
What is the enzyme that converts homocysteine into cystathione? What cofactor does it use?
cystathionine beta-synthase; uses PLP (vitamin B6)
Increased serum homocysteine can be caused by a deficiency of which three vitamins?
1) folate (vitamin B9)
2) PLP (vitamin B6)
3) cobalamin (vitamin B12)
What is the major consequence of increase serum homocysteine? How does this work?
Increase in premature CVD events due to interfering with collagen synthesis
Which enzyme produces THF from folate?
dihydrofolate reductase
Which two medications inhibit DHF reductase?
1) methotrexate
2) trimethoprim
The synthesis of what molecules use the one carbon pool (and subsequently DHF reductase)?
1) purines
2) thymidine
What is the cause of the macrocytic anemia seen in folic acid deficiency?
Decreased folate leads to decreased THF which leads to a decrease in DNA synthesis and thus cell division. This predominantly affects RBCs causing them to hemolyse
Which molecule acts as a “folate trap”?
methyl THF
How does a folate deficiency lead to increased serum homocysteine?
Methyl THF is used by methionine synthase to produce methionine from homocysteine. If there is a folate defiency, methyl THF is low and thus this reaction cannot take place leading to an accumulation of homocysteine
What is another name for the decreased DNA synthesis that can take place in folate defiency?
Mitotic lag
Other than folate defiency, where is mitotic lag also seen?
Vitamin B12 defiency
What are the two characteristic signs of folate defiency on peripheral blood smear?
1) increased size of RBCs (macrocytes)
2) hypersegmented neutrophils
What is the requirement for folate in pregnancy?
Double!
A decrease in folate causes an increased risk in what?
Neural tube defects
What is the richest source of dietary folate?
Green, leafy vegetables
How can you tell that macrocytic anemia might be present in a CBC?
MCV is elevated
What is the test used to diagnose folate deficiency?
Histidine load test
What separates folate defiency from Vitamin B12 defiency?
Neurological complications
A positive histidine load test results in what?
Presence of FIGLU in the urine
What two reactions in 1-C metabolism are clinically significant in relation to Vitamin B12?
1) homocysteine to methionine by methionine synthase or homoecysteine methyltransferase
2) methylmalonyl CoA to succinyl CoA by methylmalonyl-CoA mutase
A vitamin B12 defiency leads to what serum results?
1) increased serum homocysteine
2) increased serum (and urine) methylmalonate
How is methylmalonate responsible for the neurological complications of vitamin B12 deficiency?
Interferes with myelination
Where is Vitamin B12 stored?
liver
