L25 - 1C Metabolism and Some Products of Amino Acids

Question 1

PKU Type II is also called what? Why?

Answer 1

Malignant PKU as it is harder to treat than classical PKU

Question 2

What causes malignant PKU?

Answer 2

Deficiency of dihydrobiopterin or tetrahydrobiopterin reductase

Question 3

What are the three reactions for which BH4 is necessary?

Answer 3

1) Phe to Tyr
2) Tyr to L-dopa
3) 5-HT synthesis

Question 4

What effect does PKU II have on tyrosine?

Answer 4

Tyrosine becomes an essential AA

Question 5

What substances are produced in lower number in PKU II?

Answer 5

1) reduced melanin synthesis
2) reduced catecholamine synthesis
3) reduced tyrosine synthesis

Question 6

One-carbon metabolism links amino acid metabolism and the metabolism of what other molecules?

Answer 6

nucleotides (nucleic acids)

Question 7

What three vitamins/cofactors are necessary for 1-C transfers?

Answer 7

1) vitamin B9 (folate)
2) vitamin B12 (cobalamin)
3) SAM

Question 8

SAM is a _____ donor. It is especially important in the formation of _______. After donating its carbon, it is converted into ________.

Answer 8

1) methyl
2) epinephrine
3) homocysteine

Question 9

Homocysteine can be converted back to its original amino acid which is?

Answer 9

Methionine

Question 10

What enzyme converts homocysteine into methionine?

Answer 10

methionine synthase

Question 11

Homocysteine can be converted into ________ via the _________ pathway.

Answer 11

1) cysteine

2) transulfuration pathway

Question 12

What is the enzyme that converts homocysteine into cystathione? What cofactor does it use?

Answer 12

cystathionine beta-synthase; uses PLP (vitamin B6)

Question 13

Increased serum homocysteine can be caused by a deficiency of which three vitamins?

Answer 13

1) folate (vitamin B9)
2) PLP (vitamin B6)
3) cobalamin (vitamin B12)

Question 14

What is the major consequence of increase serum homocysteine? How does this work?

Answer 14

Increase in premature CVD events due to interfering with collagen synthesis

Question 15

Which enzyme produces THF from folate?

Answer 15

dihydrofolate reductase

Question 16

Which two medications inhibit DHF reductase?

Answer 16

1) methotrexate

2) trimethoprim

Question 17

The synthesis of what molecules use the one carbon pool (and subsequently DHF reductase)?

Answer 17

1) purines

2) thymidine

Question 18

What is the cause of the macrocytic anemia seen in folic acid deficiency?

Answer 18

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

Question 19

Which molecule acts as a “folate trap”?

Answer 19

methyl THF

Question 20

How does a folate deficiency lead to increased serum homocysteine?

Answer 20

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

Question 21

What is another name for the decreased DNA synthesis that can take place in folate defiency?

Answer 21

Mitotic lag

Question 22

Other than folate defiency, where is mitotic lag also seen?

Answer 22

Vitamin B12 defiency

Question 23

What are the two characteristic signs of folate defiency on peripheral blood smear?

Answer 23

1) increased size of RBCs (macrocytes)

2) hypersegmented neutrophils

Question 24

What is the requirement for folate in pregnancy?

Answer 24

Double!

Question 25

A decrease in folate causes an increased risk in what?

Answer 25

Neural tube defects

Question 26

What is the richest source of dietary folate?

Answer 26

Green, leafy vegetables

Question 27

How can you tell that macrocytic anemia might be present in a CBC?

Answer 27

MCV is elevated

Question 28

What is the test used to diagnose folate deficiency?

Answer 28

Histidine load test

Question 29

What separates folate defiency from Vitamin B12 defiency?

Answer 29

Neurological complications

Question 30

A positive histidine load test results in what?

Answer 30

Presence of FIGLU in the urine

Question 31

What two reactions in 1-C metabolism are clinically significant in relation to Vitamin B12?

Answer 31

1) homocysteine to methionine by methionine synthase or homoecysteine methyltransferase
2) methylmalonyl CoA to succinyl CoA by methylmalonyl-CoA mutase

Question 32

A vitamin B12 defiency leads to what serum results?

Answer 32

1) increased serum homocysteine

2) increased serum (and urine) methylmalonate

Question 33

How is methylmalonate responsible for the neurological complications of vitamin B12 deficiency?

Answer 33

Interferes with myelination

Question 34

Where is Vitamin B12 stored?

Answer 34

liver