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