B12 and Folate Flashcards

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1
Q

General structure of cobalmin

A

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

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2
Q

Cofactor and use of Metionine synthase

A
  • methyl cobalamin
  • used to resynthesize met from homocysteine, form tetrahydrofolate forms from metal tetrahydrofolate
  • homocysteeine N-methyltransferase
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3
Q

Methylmalonyl-CoA mutase (MCM)

A
  • uses 5’-deoxyadenosylcobalmin
  • methylmalonyl-CoA—>succinyl-CoA
  • 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
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4
Q

SAM

A
  • S-adenosylmethionine
  • 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
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5
Q

Methionine synthase

A
  • L-homocysteine + N5-methyltetrahydrofolate—>L-methioinine + tetrahydrofoalte
  • requires methylcobalamin (Methyl-B12)
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6
Q

Methionine to cysteine

A
  • 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+
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7
Q

Effect of B12 deficiency

A
  • 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
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8
Q

Homocysteinemia/uria

A

•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

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9
Q

Causes of B12 deficiency

A
  • 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)
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10
Q

Uses of cystein metabolites

A
  • cysteine dioxygenase: cys–>taurine (for bile salt synthesis)
  • sulfate from catabolism used as precursor fo 3’-phosphoadenosine-5’-phosphosulfate (PAPS)—>glycolipid and GAG synthesis
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11
Q

Dietary sources of B12

A

animal sources, not in plants

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12
Q

Dietary ofurce of B9

A
  • aka folic acid

- green leafy vegetables, liver, lima beans, whole-grain cereals

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13
Q

Important uses of B9

A
  • active as forms of tetraydrofolate (THF) derivatives
  • does carbon unit transfers
  • purine and thymidine synthesis
  • glycineserine
  • synthesis of methionine from homocysteine
  • degradation of histidine
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14
Q

Synthesis of folic acid

A
  • done in bacteria and plants

- enzyme: dihydropteroate synthetase is inhibited competetively by sulfonamides (most are antibiotics)

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15
Q

Synthesis of THF

A

-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
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16
Q

SerineGlycine

A

Serine hydroxymethyltransferase catalyzes:

Ser + THF Gly + N5, N5-methyleneTHF

17
Q

Histidine degradation

A
  1. Histidase: his—>urocanic acid + NH3
  2. some more steps
  3. Formiminotransferase cyclodeaminase: N-Formimoglutamate (FLGlu) + THF —-> 5-Formimino-THF + glutamate
18
Q

N-Formimoglutamate

A
  • 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
19
Q

Histidinemia

A
  • caused by deficiency of histidinase

- his—>urocanic acid + NH3

20
Q

Causes and effects of Folate deficiency

A
  • 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