One Carbon Metabolism

Question 1

Blood _____ is one clinical measure of kidney function.

Answer 1

Creatine

Question 2

Why is creatine a good measure of kidney function?

Answer 2

Because it is freely filtered by the kidney and produced in the body at a constant rate.

Question 3

What is creatine’s purpose in the body?

Answer 3

Creatine is part of the phosphagen system that serves to transport high energy phosphate groups and buffer cellular ADP levels

Question 4

Creatine and phosphocreatine spontaneously breakdown into _____. As such it is a good reflection of total body _________.

Answer 4

Creatinine

Muscle mass

Question 5

What does creatine have to do with one carbon metabolism?

Answer 5

Synthesis of creatine requires the transfer of a methyl group from methionine, which is part of the one carbon metabolic cycle that involves S-Adenosylmethionine which is the most common methyl donor in the body. Creatine synthesis is one of the largest needs for methylation in the body.

Question 6

In one carbon metabolic cycle, which compound will accumulate if there is a vitamin B12 deficiency?

Answer 6

Homocysteine

Question 7

____ accepts methyl group from N⁵-MTHF and transfers it to homocysteine to make methionine

Answer 7

Vitamin B12

Question 8

Which enzyme in the creatine synthesis pathway is a clinical marker for muscle damage?

Answer 8

Creatine kinase

Question 9

What type of vitamin is folate?

Answer 9

Vitamin B9

Question 10

What traps THF in the cell?

Answer 10

Polyglutmation

Question 11

Tetrahydrofolate can be used to donate a methyl group. Where does the methyl group on THF come from?

Answer 11

Amino acids, mostly serine

Question 12

What cofactor is needed to produce THF from amino acids?

Answer 12

PLP

Question 13

What are 3 pathways that THF can donate methyl groups to?

Answer 13

SAM synthesis

Thymidylate synthesis

Purine biosynthesis

Question 14

What effect would folate deficiency have at the cellular level?

Answer 14

DNA synthesis will be reduced because cells will not be able to synthesize appropriate amounts of nucleotides. As such, rapidly dividing cells may begin the cell cycle but they will eventually stall during DNA replication and the stalled replication forks will cause apoptosis.

Question 15

What tissues/organ systems would be most affected by folate deficiency?

Answer 15

GI mucosa

Bone marrow (anemia)

Skin

Question 16

What clinical presentation is characeristic of folate deficiency?

Answer 16

Macrocytic anemia (blood cells are fewer in number but are larger) and inflammation (from increase in cell size not apoptosis)

Question 17

Explain how a person can present with folate deficiency but have normal levels of folate in their blood.

Answer 17

They could have a functional folate deficiency that is actually caused by a deficiency in vitamin B12. If VitB12 is low, then homocysteine will accumulate and any folate that is produced will be trapped in the N-MTHF form because there is no way to convert it to THF without VitB12. Also, N-MTHF is only used in the SAM synthesis reaction so it cannot be utlized for other reactions that require folate. It is also very stable so it will not be broken down. This results in an accumulation of N-MTHF so folate levels appear normal but that form of folate is non-functional so the person appears to have folate deficiency.

Question 18

What 2 compounds will be elevated in a person with vitamin B12 deficiency?

Answer 18

Methylmalonyl coA and homocysteine

Question 19

What neurological symptoms are associated with Vitamin B12 deficiency?

Answer 19

Tingling and burning in extremeties b/c Vit B 12 is needed to ensure proper myelination of neurons especially those involved in proprioception, so w/o enough B12 nerves will be damaged