One Carbon Metabolism Flashcards
Blood _____ is one clinical measure of kidney function.
Creatine
Why is creatine a good measure of kidney function?
Because it is freely filtered by the kidney and produced in the body at a constant rate.
What is creatine’s purpose in the body?
Creatine is part of the phosphagen system that serves to transport high energy phosphate groups and buffer cellular ADP levels
Creatine and phosphocreatine spontaneously breakdown into _____. As such it is a good reflection of total body _________.
Creatinine
Muscle mass
What does creatine have to do with one carbon metabolism?
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.
In one carbon metabolic cycle, which compound will accumulate if there is a vitamin B12 deficiency?
Homocysteine
____ accepts methyl group from N5-MTHF and transfers it to homocysteine to make methionine
Vitamin B12
Which enzyme in the creatine synthesis pathway is a clinical marker for muscle damage?
Creatine kinase
What type of vitamin is folate?
Vitamin B9
What traps THF in the cell?
Polyglutmation
Tetrahydrofolate can be used to donate a methyl group. Where does the methyl group on THF come from?
Amino acids, mostly serine
What cofactor is needed to produce THF from amino acids?
PLP
What are 3 pathways that THF can donate methyl groups to?
SAM synthesis
Thymidylate synthesis
Purine biosynthesis
What effect would folate deficiency have at the cellular level?
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.
What tissues/organ systems would be most affected by folate deficiency?
GI mucosa
Bone marrow (anemia)
Skin
What clinical presentation is characeristic of folate deficiency?
Macrocytic anemia (blood cells are fewer in number but are larger) and inflammation (from increase in cell size not apoptosis)
Explain how a person can present with folate deficiency but have normal levels of folate in their blood.
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.
What 2 compounds will be elevated in a person with vitamin B12 deficiency?
Methylmalonyl coA and homocysteine
What neurological symptoms are associated with Vitamin B12 deficiency?
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
