B12 and Folate Flashcards Preview

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Flashcards in B12 and Folate Deck (20):

General structure of cobalmin

vit B12, corrin ring system, has colbalt (CO)


Cofactor and use of Metionine synthase

•methyl cobalamin
•used to resynthesize met from homocysteine, form tetrahydrofolate forms from metal tetrahydrofolate
•homocysteeine N-methyltransferase


Methylmalonyl-CoA mutase (MCM)

•uses 5'-deoxyadenosylcobalmin
•for odd-chain fatty acid oxidation and metabolism of ile, val, thre, met (get converted to propionyl-CoA)
•propionyl-CoA (3 carbon product of odd-chain fatty acid β-oxidation) carboxylated to d-methylmalonyl-CoA (propionyl-coa carboxylase, biotin, atp, hco3-), which is converted to the L form by a specific epimerase, then MCM will work



•S-Adenosyl-methionine syntetase: L-Met + ATP-->SAM + Pi + PPi (requires Mg2+)
•used as a methyl group donor by methyltransferases (ex: norepinepherine-->epinephrine; PE-->PC; mRNA methylation (5' cap)
•S-adenosylhomocysteins (SAH) is product of methyltranferase rxn
•SAH is degraded to L-homocysteine


Methionine synthase

•L-homocysteine + N5-methyltetrahydrofolate--->L-methioinine + tetrahydrofoalte
•requires methylcobalamin (Methyl-B12)


Methionine to cysteine

•S-Adenosyl-methionine syntetase: L-Met + ATP-->SAM + Pi + PPi (requires Mg2+)
•methyltransferase: SAM-->S-adenosylhomocysteine
•SAH + H2O --> homocysteine + adenosine
•cystathione β-synthase (B6/PLP): homocysteine + serine-->cystathionine + H2O
•γ-cystathionase (B6/PLP): cystathione + H2O--->cysteine + α-ketobutyrate + NH4+


Effect of B12 deficiency

•homocysteine cannot be recycled by methionine synthase and accumulates (homocysteinemeia)
•THF trapped in methyl-THF form
•inhibits purine synthesis and synthesis of dTMP which require other forms of THF (and thus DNA replication and transcription)
•accumulation of abnormal fatty acids-->CNS effects (irreversable)
•pernicious anemia (treat with lifetime IM cyanocobalamin injections)
•megaloblastic anemia (DNA systhesis of RBC precursors inibited, cells just grow since they can't make it through M phase) (treat with folate and B12)-->anemia is reversable
•progressive peripheral neuropathy
•methlmaonyl acidura
•takes years to develop



•associated with B12, folate (methioinine synthase), or B6 deficiencies (cystationine synthetase and lyase/gamma cystathioininase)

•damages blood vessels and poses risk for thrombosis
•lipid oxidation and increased platelet aggregation-->fibrosis adn cacification fo aterosclerotic plaques

-hyperhomocysteinemia: homocystinuria caused by deficiency of cystationine synthase; lens dislocation after age 3 and other ocular abnormalities, osteoporosis in childhood, mental retardation, atheromas


Causes of B12 deficiency

•pernicious anemia-->lack of intrinsic factor due to autoimmunie destruction of parietal cells
•pure vegan diet
•chronic pancreatitis (can't clave of R factor)
•chron's disease (terminal ileal disease)


Uses of cystein metabolites

-cysteine dioxygenase: cys-->taurine (for bile salt synthesis)

-sulfate from catabolism used as precursor fo 3'-phosphoadenosine-5'-phosphosulfate (PAPS)--->glycolipid and GAG synthesis


Dietary sources of B12

animal sources, not in plants


Dietary ofurce of B9

-aka folic acid
-green leafy vegetables, liver, lima beans, whole-grain cereals


Important uses of B9

-active as forms of tetraydrofolate (THF) derivatives
-does carbon unit transfers
-purine and thymidine synthesis
-synthesis of methionine from homocysteine
-degradation of histidine


Synthesis of folic acid

-done in bacteria and plants
-enzyme: dihydropteroate synthetase is inhibited competetively by sulfonamides (most are antibiotics)


Synthesis of THF

-Dihyrofolate reductase
Folic acid + 2 NADPH ------>THF + 2 NADP+

-Inhibited by methotrexate, used to treat neoplastic disesase, psoriasis adn rheumatoid arthritis
-2 step reaction
-carbon units are carried by THF bound to N5 and/or N10



Serine hydroxymethyltransferase catalyzes:
Ser + THF Gly + N5, N5-methyleneTHF


Histidine degradation

1. Histidase: his--->urocanic acid + NH3
2. some more steps
3. Formiminotransferase cyclodeaminase: N-Formimoglutamate (FLGlu) + THF ----> 5-Formimino-THF + glutamate



-intermediate in histidine degragation
-gives formimino group to THF forming glutamate
-elevated following ingestion of large dose of histidine in Folic acid deficiency
-FLGlu excretion test used to diagnose deficiency of folic acid



-caused by deficiency of histidinase
-his--->urocanic acid + NH3


Causes and effects of Folate deficiency

-diet lacking in fruits and vegetables
-chemotheraputics like methotrexate or trimethoprim which are dihydrofolate reductase inhibitors-->prevent purine and thymidine synthesis-->kill blast cells and acuse macrocytic anemia
-phenytoin (inhibits intestinal conjugase)
-oral contraceptives (inhibits absorption of monoglutamate in jejunum)
-alcohol (block absorption)
-rapidly growing cancers (use more folic acid than normal cells)
-small bowel malabsorption (i.e: celiac)
-sulfa drugs (sulfanilamide) inhibit folic acid synthesis by intestinal flora

-most common in pregnant women (linked with neural tube defects) and alcoholics (important too in malnourished individuals)

-deficiency causes homocystinuria/emia and megaloblastic anemia
-develops in 3-4 months
-increased cardiovascular disease risk