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1-Carbon Metabolism
USCSOM: One-Carbon Metabolism
| Question | Answer |
|---|---|
| What are the 3 main carriers of reduced one-carbon units? | derivatives of THF acid, SAM,vit B12 |
| What are the sources of 1 carbon units? | Ser, Gly, His, Formate, Formaldehyde |
| FH4 is derived from what vitamin? | folic acid (folate) |
| Folate is synthesized from what 3 precursors? | pteridine ring, PABA, glutamate |
| What is the key enzyme involve din FH4 synthesis from Folate? | dihydrofolate reductase |
| Where are the carbon units attatched to on FH4? | N5 or N10 |
| What AA is the major source of one-carbon groups carried by FH4? | Ser |
| What path does His take to get to its FH4 derivative? | His, FIGLU, 5-formimino-FH4, methenyl-FH4 |
| Glycine forms what FH4 derivative? | methylene-FH4 |
| Formaldehyde forms what FH4 derivative? | Methylene-FH4 |
| Formate forms what FH4 derivative? | Formyl-FH4 |
| Reoxidation of FH4 derivatives cannot occur at what level of oxidation? | Methyl-FH4 |
| What are the direct recipients from FH4 carbon pool? | dUMP, purine precursors, Gly, B12 |
| dUMP is methylated to dTMP by what enzyme? | thymidylate synthase |
| What is the source of the free carbon for dTMP formation? | methylene-FH4 |
| What is the enzyme the catalyzes the reduction of FH2 to FH4? | dihydrofolate reductase |
| What chemotherapy agents disrupt dTMP formation? | Methotrexate, 5-Fluorouracil |
| What does methotrexate inhibit? | dihydrofolate reductase |
| What does 5-Fluorouracil inhibit? | thymidylate synthase |
| Cobalamine is also known as ______ | Vitamin B12 |
| What is the major source of Vitamin B12? | dietary meats, dairy |
| What proteins help vitB12 absorb from the gut? | R-binders, Inrinsic factgors, proteases |
| What protein carriers vit B12 in the blood to the liver? | transcobalamin II |
| What two reactions in the body involve vit B12? | 1. methyl transfer from FH4 to homocysteine to form methionine 2. methylmalonyl CoA to Succinyl CoA |
| What is the form of B12 forming methionine? | methyl-B12 |
| What is the form of B12 forming Succinyl CoA? | 5'-adenosylcobalamin |
| What are clinical signs of B12 deficiency? | hematopoisis and neurological signs |
| B12 hematopoietic problems cause what secondary deficiency? | folate deficiency |
| B12 deficiency leads to neurological problems and a build up of what substance? | Methyl-malonyl CoA |
| What is SAM? | S-adenosyl methionine |
| SAM is synthesized from what two things? | methionine and ATP |
| Mutations in what enzymes lead to homocysteine elevations? | methionine synthase, n5,n10 methylene FH4 reductase, cystathionine-beta-synthase |
| Elevated homocysteine is a risk factor for what disease? | cardiovascular disease |
| Biotin is involved in transfering what type of carbons? | oxidized on-carbon units |
| What enzyme is coupled with biotin to move an oxidized-carbon? | pyruvate carboxylase |
| Enzyme bound biotin is linked to what AA via an amide linkage? | lysine residue |
| What are the recipients of one-carbon transfers via FH4? | dTMP, ser, purines, vit B12 |
| Substantially higher doses of folate are RXed for pregnant women to prevent what new born defect? | spina bifida |
| What is the main pathway for obtaining folate in humans? | absorbtion from the diet |
| What category of drugs are prescribed to interfere with folate synthesis in bacterial infections? | Sulfa drugs |
| What is considered the active form of folate? | FH4 |
| Serine forms what FH4 derivative? | N5,N10-methylene FH4 |
| His forms what FH4 derivative? | N5,N10-methenyl FH4 |
| Formaldehyde is produced during the catabolism of methyl groups off of what molecules? | choline and Epi |
Created by:
jlellerm
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